Blood coagulation analyzer, method for analyzing fibrinogen and clinical decision support system

Abstract

The embodiment of the invention relates to a blood coagulation analyzer, a fibrinogen analysis method and a clinical decision support system. The blood coagulation analyzer comprises a sample preparation part which is used for preparing a determination sample by using to-be-detected plasma from a to-be-detected blood sample and a detection reagent; the detection part is used for detecting the test sample; the controller is used for acquiring detection information representing reduction of fibrinogen in the to-be-detected plasma, and responding to the detection information: controlling the sample preparation part to prepare a first determination sample at a first dilution ratio and a second determination sample at a second dilution ratio, and controlling the detection part to respectively detect the first determination sample and the second determination sample, and determining the cause of fibrinogen reduction in the to-be-detected plasma at least according to the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio and a reference curve, and the reference curve represents the relationship between the coagulation time and the dilution ratio of the reference plasma.

Description

Technical Field

[0001] This application relates to the field of in vitro diagnostic devices, and in particular to a coagulation analyzer, a method for analyzing fibrinogen in blood samples, and a clinical decision support system. Background Technology

[0002] Fibrinogen (FIB) is an important coagulation factor and a crucial protein involved in the coagulation and hemostasis processes. Fibrinogen is primarily synthesized by the liver and, under the action of thrombin, is broken down into fibrin peptides A and B and fibrin monomers. These fibrin monomers spontaneously couple to form fibrin polymers. Under the influence of stabilizing factors (factor FXIII) and Ca2+ ions, these fibrin polymers further bind together with other blood cells, eventually coagulating to form a thrombus.

[0003] Decreased fibrinogen activity leads to impaired blood clotting function and increases the risk of bleeding. Therefore, it is particularly important to be able to quickly and accurately determine the cause of decreased fibrinogen. Summary of the Invention

[0004] Therefore, the objective of this application is to accurately determine the cause of decreased fibrinogen in blood samples based on the principle of parallel trials.

[0005] The first aspect of this application provides a coagulation analyzer, comprising:

[0006] The sample preparation component is designed to prepare a test sample using plasma from the blood sample to be tested and detection reagents.

[0007] A detection component is configured to detect the test sample;

[0008] The controller is configured to acquire detection information characterizing a decrease in fibrinogen in the plasma to be tested, and in response to the acquisition of the detection information:

[0009] The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample.

[0010] The detection component is controlled to detect the first test sample to obtain the first solidification time of the first test sample.

[0011] The sample preparation component is controlled to dilute a second portion of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested is mixed with thrombin reagent to prepare a second test sample.

[0012] The detection component is controlled to detect the second test sample to obtain the second solidification time of the second test sample, and

[0013] The reason for the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0014] A second aspect of this application provides a coagulation analyzer, comprising:

[0015] The sample preparation component is designed to prepare a test sample using plasma from the blood sample to be tested and detection reagents.

[0016] A detection component is configured to detect the test sample;

[0017] Controller, settings for:

[0018] Obtain the first fibrinogen concentration value of the plasma to be tested.

[0019] Based on the first fibrinogen concentration value, it is determined whether the plasma to be tested has a decrease in fibrinogen.

[0020] If it is determined that there is no decrease in fibrinogen in the plasma to be tested, then the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value;

[0021] If it is determined that the plasma to be tested has decreased fibrinogen, a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of a sample prepared by diluting the plasma to be tested with a diluent and mixing the diluted plasma with thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of a sample prepared by diluting a reference plasma with the diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decreased fibrinogen in the plasma to be tested.

[0022] A third aspect of this application provides a coagulation analyzer, comprising:

[0023] The sample preparation component is designed to dilute the plasma to be tested in the blood sample and mix the diluted plasma with the test reagent to prepare the test sample.

[0024] A detection component is configured to detect the test sample;

[0025] Controller, settings for:

[0026] The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample.

[0027] The detection component is controlled to detect the first test sample to obtain the first solidification time of the first test sample.

[0028] The sample preparation component is controlled to dilute a second portion of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested is mixed with thrombin reagent to prepare a second test sample.

[0029] The detection component is controlled to detect the second test sample to obtain the second solidification time of the second test sample.

[0030] A sample curve is determined at least based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios.

[0031] To determine whether there is a preset relationship between the sample curve and the reference curve, in order to determine the reason for the decrease in fibrinogen in the plasma to be tested, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0032] The fourth aspect of this application provides a method for analyzing fibrinogen in a blood sample, comprising:

[0033] Determine whether the blood sample to be tested has a decrease in fibrinogen;

[0034] When it is determined that the blood sample to be tested has decreased fibrinogen, the following steps are performed:

[0035] The first portion of the plasma to be tested in the blood sample to be tested is diluted with a diluent at a first dilution ratio, and the diluted first portion of plasma to be tested is mixed with thrombin reagent to prepare a first test sample.

[0036] The first test sample is tested to obtain the first solidification time of the first test sample.

[0037] The second portion of the plasma to be tested from the blood sample was diluted with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested was mixed with thrombin reagent to prepare a second test sample;

[0038] The second test sample is tested to obtain the second solidification time of the second test sample; and

[0039] The reason for the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0040] The fifth aspect of this application provides a method for analyzing fibrinogen in a blood sample, comprising:

[0041] Obtain the first fibrinogen concentration value of the plasma in the blood sample to be tested;

[0042] Based on the first fibrinogen concentration value, it is determined whether the plasma to be tested has a decrease in fibrinogen;

[0043] If it is determined that there is no decrease in fibrinogen in the plasma to be tested, then the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value;

[0044] If it is determined that the plasma to be tested has decreased fibrinogen, a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of a sample prepared by diluting the plasma to be tested with a diluent and mixing the diluted plasma with thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of a sample prepared by diluting a reference plasma with the diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the cause of the decreased fibrinogen in the plasma to be tested.

[0045] The sixth aspect of this application provides a method for analyzing fibrinogen in a blood sample, comprising:

[0046] Obtain plasma from the blood sample to be tested;

[0047] The first portion of the plasma to be tested is diluted with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample;

[0048] The first test sample is tested to obtain the first solidification time of the first test sample.

[0049] The second portion of the plasma to be tested from the blood sample was diluted with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested was mixed with thrombin reagent to prepare a second test sample;

[0050] The second test sample is tested to obtain the second solidification time of the second test sample;

[0051] A sample curve is determined at least based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios.

[0052] To determine whether there is a preset relationship between the sample curve and the reference curve, in order to determine the reason for the decrease in fibrinogen in the plasma to be tested, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0053] The seventh aspect of this application provides a clinical decision support system, comprising:

[0054] Non-transitory machine-readable memory that stores executable instructions; and

[0055] One or more processors are configured to execute the executable instructions to perform the following operations:

[0056] Obtain a sample curve and a reference curve, wherein the sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios and the different dilution ratios; and the reference curve characterizes the relationship between the coagulation time of a sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0057] Determine whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested; and

[0058] Output the corresponding prompt message on the user interface based on the determined reason.

[0059] In the embodiments proposed in various aspects of this application, corresponding test samples are prepared from the plasma to be tested at at least two different dilution ratios (e.g., a first dilution ratio and a second dilution ratio) and tested to obtain the corresponding coagulation time, or to obtain a sample curve characterizing the relationship between the coagulation time of the plasma to be tested and the dilution ratio. Then, based on the obtained coagulation time and its corresponding dilution ratio, and the reference curve characterizing the relationship between the coagulation time and the dilution ratio of a reference plasma, or based on the obtained sample curve and the reference curve, the user can be assisted in accurately determining the cause of the decrease in fibrinogen in the plasma to be tested, so that the user can take targeted countermeasures. Attached Figure Description

[0060] Figure 1 This diagram illustrates the structure of a coagulation analyzer according to an embodiment of this application.

[0061] Figure 2 Show Figure 1 A schematic diagram of the sample preparation component of a coagulation analyzer.

[0062] Figure 3 The sample curve and corresponding reference curve are shown for blood samples with hypofibrinogenemia;

[0063] Figure 4 The sample curve and corresponding reference curve for blood samples with jaundice interference are shown;

[0064] Figure 5 The sample curve and corresponding reference curve are shown for blood samples with hereditary abnormal fibrinogenemia;

[0065] Figure 6 The sample curve and corresponding reference curve are shown for blood samples with acquired dysfibrinogenemia.

[0066] Figure 7 The sample curves and corresponding reference curves for blood samples resistant to IIa interference are shown.

[0067] Figure 8 An exemplary flowchart is shown, according to an embodiment of the present application, of a coagulation analyzer analyzing the reasons for decreased fibrinogen levels in a test plasma.

[0068] Figure 9Another exemplary flowchart illustrates the reason for the decrease in fibrinogen in the plasma sample analyzed by a coagulation analyzer according to an embodiment of this application;

[0069] Figure 10 An exemplary flowchart of a method for analyzing fibrinogen in a blood sample according to an embodiment of this application is shown;

[0070] Figure 11 An exemplary flowchart illustrating another method for analyzing fibrinogen in a blood sample according to an embodiment of this application is shown; and

[0071] Figure 12 An exemplary flowchart is shown for another method for analyzing fibrinogen in a blood sample according to an embodiment of this application. Detailed Implementation

[0072] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0073] It should be noted that the terms "first, second, third, and fourth" used in the embodiments of this application are merely to distinguish similar objects and do not represent a specific order of objects. It can be understood that "first, second, third, and fourth" can be interchanged in a specific order or sequence where permitted.

[0074] As mentioned in the background section, decreased fibrinogen activity leads to impaired coagulation function and a risk of bleeding. Therefore, it is necessary to accurately determine the cause of decreased fibrinogen so that doctors can take appropriate measures.

[0075] Clauss' method and algorithms are commonly used in related technologies to detect fibrinogen in blood samples.

[0076] In the Clauss method, the plasma to be tested is typically diluted first, and then thrombin reagent is added to the diluted plasma. The plasma coagulates, and the time required for coagulation is negatively correlated with the fibrinogen (FIB) content. In this experiment, thrombin reagent is used in relative excess, and the reaction rate is determined by the activity of the substrate (fibrinogen). The actual FIB content of the plasma can be obtained from a standard curve determined by certified reference materials (CRMs, including international or national reference materials), manufacturer reference materials, or standards. It is understood that the standard curve describes the relationship between FIB concentration (or activity) and coagulation time.

[0077] In the algorithm, when testing plasma for parameters such as activated partial thromboplastin time (APTT) and prothrombin time (PT), the change in transmitted / scattered light flux or absorbance from the start to the end of the coagulation reaction is positively correlated with the FIB content. Therefore, for tests such as APTT / PT / TT / FIB, after adding the test reagent to the plasma, the change in transmitted / scattered light flux (or absorbance) from the start to the end of the coagulation reaction is measured. The FIB concentration is then obtained by referring to a standard curve using this change in flux or absorbance. During the coagulation reaction, only the conversion of fibrinogen to fibrin causes a change in transmitted / scattered light intensity; therefore, the fibrinogen concentration can be "inferred" from this. However, the rate of fibrinogen conversion cannot be examined. The FIB concentration measured by this method can be considered as the antigen concentration.

[0078] There are many reasons for decreased fibrinogen levels, some of the more common ones are as follows:

[0079] 1) Decreased fibrinogen (hypofibrinogenemia, abbreviated as: hypofibrinogen), for example, liver disease leading to reduced synthesis, disseminated intravascular coagulation (DIC) leading to accelerated consumption, use of fibrinolytic drugs such as batroxobin, etc.

[0080] 2) Abnormal fibrinogen structure and reduced activity, also known as dysfibrinogenemia (CD), includes hereditary and acquired dysfibrinogenemia. Hereditary dysfibrinogenemia is caused by gene mutations leading to abnormal amino acid sequences or structures of fibrinogen, and has a family history. Most cases do not affect coagulation function, but a small number can lead to thrombosis or bleeding. Acquired dysfibrinogenemia is caused by certain proteins interfering with the process of fibrinogen converting into fibrin, resulting in reduced fibrinogen activity. For example, autoimmune diseases can produce antibodies that inhibit fibrin polymerization or delay the release of fibrin peptides. Acquired dysfibrinogenemia does not have a family history.

[0081] 3) The FIB testing process is interfered with, for example, by the use of antithrombin (IIa) anticoagulants or by HIL (HIL stands for hemolysis, icterus, and lipemia).

[0082] Therefore, identifying the causes of decreased fibrinogen is of great significance for doctors' subsequent treatment or diagnostic measures.

[0083] To improve the accuracy of fibrinogen reporting results and reduce reporting costs, related technologies propose that abnormal fibrinogenemia can be identified by the ratio of FIB antigen to activity. Specifically, the FIB antigen content (dFIB) is detected by the PT algorithm, and the FIB activity (FIB-c) is detected by the Clauss method.

[0084] However, this method can only identify abnormal fibrinogenemia and cannot identify other causes of decreased fibrinogen.

[0085] Based on this, embodiments of this application propose using the principle of parallel testing to assist users in determining the cause of decreased fibrinogen in blood samples.

[0086] like Figure 1 As shown, this application first provides a coagulation analyzer 100. The coagulation analyzer 100 is used to determine and analyze the amount and activity of specific substances related to coagulation function in blood samples. Specifically, it is used to test blood samples for various coagulation test items to obtain the coagulation test results of the blood samples.

[0087] In some embodiments, coagulation tests include, but are not limited to, APTT (Active Partial Thromboplastin Time), PT (Prothrombin Time), TT (Thrombin Time), FIB, LA (Lupus Anticoagulan), ECT (Ecarin Clotting Time), AT (Antithrombin), PC (Protein C), PLG (Plasminogen), DD (D-dimer), and FDP (Fibrin Degradation Product).

[0088] like Figure 1 As shown, the coagulation analyzer 100 includes a sample preparation component 110, a detection component 120, and a controller 130.

[0089] The sample preparation unit 110 is configured to prepare a test sample from the test plasma and test reagents, such as coagulation reagents, from the blood sample to be tested.

[0090] In some embodiments, the sample preparation component 110 is configured to dilute the plasma to be tested in the blood sample to be tested, and to mix the diluted plasma to be tested with the test reagent to prepare the test sample.

[0091] For example, the sample preparation component 110 is configured to dilute the plasma to be tested with a diluent at a selected dilution ratio, and to mix the diluted plasma to be tested with a test reagent to prepare a test sample.

[0092] In the embodiments of this application, the dilution ratio refers to the ratio of the amount of plasma used to the amount of plasma before and after the addition of diluent. For example, the ratio of the volume of plasma used to the amount of plasma before and after the addition of diluent, i.e., dilution ratio = V1 / V2, where V1 is the volume of plasma used and V2 is the sum of the volume of plasma used and the volume of diluent added to the plasma.

[0093] In some embodiments, the detection reagent is a coagulation reagent corresponding to the respective coagulation test. A coagulation reagent can be understood as a reagent that triggers the coagulation reaction, and may also be called a triggering reagent. For example, when the coagulation test is PT measurement, the detection reagent is a PT measurement reagent; when the coagulation test is TT measurement, the detection reagent is a TT measurement reagent; when the coagulation test is APTT measurement, the detection reagent is an APTT measurement reagent; when the coagulation test is FIB measurement, the detection reagent is a FIB measurement reagent, such as thrombin reagent; when the coagulation test is LA measurement, the detection reagent is an LA measurement reagent; when the coagulation test is ECT measurement, the detection reagent is an ECT measurement reagent, etc.

[0094] It is understood here that commercially available reagent kits corresponding to coagulation testing items can be used in the embodiments of this application.

[0095] The detection component 120 is configured to detect the test sample. For example, the detection component 120 is configured to collect relevant information about the solidification reaction process of the test sample.

[0096] In some embodiments, the detection component 120 may be configured to detect the test sample based on any of the optical, magnetic bead, electrochemical, and microfluidic methods.

[0097] As one implementation, the detection component 120 can be configured as a photometric component that measures the photometric value of the test sample based on an optical method. For example, the detection component 120 includes at least a light source and a light-receiving device, wherein the light source is used to illuminate the test sample, and the light-receiving device is used to collect information about the light (such as transmitted light and / or scattered light) after illuminating the test sample; the information collected by the light-receiving device can also be referred to as optical information. Specifically, the test sample can be illuminated by the light source within a set time after the addition of the coagulating reagent, and the optical information of the scattered light and / or transmitted light after the light source illuminates the test sample can be obtained. In one example, the optical information can be the change in luminous flux, the change in absorbance, etc.

[0098] As some implementation methods, the detection component 120 can be configured to perform optical measurements on the test sample based on coagulation time method, synthetic matrix method, and immunoturbidimetric method. Here, the coagulation time method is a method for detecting the plasma coagulation process by detecting changes in transmitted light and / or scattered light, and its measurement items include, for example, PT, APTT, FIB, and LA. The synthetic matrix method measures items such as AT-III, and the immunoturbidimetric method measures items such as D-dimer and FDP.

[0099] The controller 130 is configured to control the sample preparation component 110 and the detection component 120, and to process and analyze the information detected by the detection component 120.

[0100] Here, the controller 130 is communicatively connected to the sample preparation component 110 and the detection component 120 to control the operation of the sample preparation component 110 and the detection component 120.

[0101] In some embodiments, the controller 130 may include a processor and a computer-readable storage medium storing computer-readable instructions that, when executed by the processor, cause the processor to perform various steps of a coagulation test.

[0102] As some implementations, the processor in the embodiments of this application may include, but is not limited to, a central processing unit (CPU), a micro controller unit (MCU), a field-programmable gate array (FPGA), a digital signal processor (DSP), and other devices used to interpret computer instructions and process data in computer software.

[0103] As some implementations, the memory in the embodiments of this application can be volatile memory or non-volatile memory, or both. Non-volatile memory can be read-only memory (ROM), programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), ferromagnetic random access memory (FRAM), flash memory, magnetic surface memory, optical disc, or compact disc read-only memory (CD-ROM); magnetic surface memory can be disk storage or magnetic tape storage. Volatile memory can be random access memory (RAM), which is used as an external cache. By way of example, but not limitation, many forms of RAM are available, such as Static Random Access Memory (SRAM), Synchronous Static Random Access Memory (SSRAM), Dynamic Random Access Memory (DRAM), Synchronous Dynamic Random Access Memory (SDRAM), Double Data Rate Synchronous Dynamic Random Access Memory (DDRSDRAM), Enhanced Synchronous Dynamic Random Access Memory (ESDRAM), SyncLink Dynamic Random Access Memory (SLDRAM), and Direct Rambus Random Access Memory (DRRAM).The memories described in the embodiments of this application are intended to include, but are not limited to, these and any other suitable types of memories.

[0104] Furthermore, the controller 130 may also include a communication interface that communicates with the processor and a computer-readable storage medium via a bus. Additionally, this communication interface is also communicatively connected to the sample preparation unit 110 and the detection unit 120.

[0105] As one implementation method, the communication interface can be an interface using any known communication protocol. The communication interface can communicate with the outside world via a network, and the controller can transmit data with any device connected through the communication interface using a specific communication protocol.

[0106] As previously described, in some embodiments, the detection component 120 can detect the test sample based on any of the optical, magnetic bead, electrochemical, and microfluidic methods to obtain relevant information about the coagulation reaction process of the test sample. Here, the controller 130 can further use the relevant information obtained by the detection component 120 to determine the coagulation time of the test sample. It is understood that the coagulation time represents the duration from the start time of the coagulation reaction of the test sample to the end time of the coagulation reaction, and can be denoted as CT (Coagulation Time).

[0107] Figure 2 A specific example of a coagulation analyzer according to an embodiment of this application is shown.

[0108] exist Figure 2 In the example shown, the sample preparation component 110 of the coagulation analyzer 100 includes a reaction cup loading section 210, a sample injection section 220, a sample dispensing section 230, a reagent carrying section 240, and a reagent dispensing section 250.

[0109] The reaction vessel loading unit 210 is used to supply and transport empty reaction vessels. For example, the reaction vessel loading unit 210 can load empty reaction vessels onto the dispensing tray.

[0110] The sample injection unit 220 is used to carry the container containing the plasma to be tested and to move it to the appropriate position, such as the position where the sample dispensing unit 230 draws up the plasma.

[0111] The sample dispensing unit 230 is used to draw a portion of the plasma to be tested from the sample injection component 220 and dispense it into a reaction cup to be added, for example, into an empty reaction cup located in the dispensing tray. For example, the sample dispensing unit 230 may include a sample needle that can move in two or three dimensions in space via a two-dimensional or three-dimensional drive mechanism, so that the sample needle can move to the position to draw the plasma to be tested and to the reaction cup to be added, and dispense the drawn plasma to be tested into the reaction cup.

[0112] The reagent carrier 240 is used to carry test reagents, such as coagulation reagents. For example, the reagent carrier 240 may include a reagent tray 241 with a disc-shaped structure or a ring-shaped structure. The reagent tray has multiple positions for carrying reagent containers. The reagent tray can rotate and drive the reagent containers it carries to rotate, so as to rotate the reagent containers to a specific position, such as the position where the test reagent is drawn up by the reagent dispensing unit 250.

[0113] In some embodiments, the reagent carrier 240 is also used to carry diluent. The reagent carrier 240 may also include a diluent tray 242 with a disc-shaped structure or a ring-shaped structure. The diluent tray has multiple positions for carrying diluent containers. The diluent tray can rotate and drive the diluent containers it carries to rotate so that the diluent containers are rotated to a specific position, such as the position where the reagent dispensing part 250 draws up the diluent.

[0114] In some embodiments, the reagent tray and the diluent tray are arranged concentrically and rotate independently of each other, for example, the reagent tray is arranged on the outer ring and the diluent tray is arranged on the inner ring.

[0115] The reagent dispensing unit 250 is used to draw test reagents from the reagent container carried by the reagent carrier 240 and dispense them into a reaction cup to be added, so as to form a test sample in the reaction cup. For example, the reagent dispensing unit 250 may include a reagent needle 251, which is capable of two-dimensional or three-dimensional movement in space by a two-dimensional or three-dimensional driving mechanism, so that the reagent needle can move to the position for drawing test reagents and to the reaction cup to be added, and dispense the drawn test reagents into the reaction cup.

[0116] In some embodiments, the reagent dispensing unit 250 is also used to draw diluent from the diluent container carried by the reagent carrier 240 and discharge it into the reaction cup to which diluent is to be added. For example, the reagent dispensing unit 250 may include a diluent needle 252, which is capable of two-dimensional or three-dimensional movement in space via a two-dimensional or three-dimensional driving mechanism, thereby enabling the diluent needle to move to the position for drawing diluent and to the reaction cup to which diluent is to be added, and to discharge the drawn diluent into the reaction cup.

[0117] In some embodiments, the diluent needle is arranged near the injection section 220, while the reagent needle is arranged near the detection component 120.

[0118] In some embodiments, the diluent needle and the sample needle can be the same needle.

[0119] In some embodiments, the coagulation analyzer 100 may further include an incubation section (not shown) for placing reaction cups to incubate the liquid within the reaction cups. For example, the incubation section may be configured as an incubation tray with a disc-shaped structure having one or more placement positions for placing reaction cups. The incubation tray is rotatable and can move the reaction cups in its placement positions to regulate the reaction cups and the liquid within them within the incubation tray (e.g., incubation at 37 degrees Celsius for 5 minutes). For example, the incubation section may be used to place reaction cups containing test plasma and diluent to incubate the mixture of the test plasma and diluent.

[0120] In some embodiments, the coagulation analyzer may also include a transfer component, such as a robotic arm, for transferring reaction cups, for example, transferring reaction cups from a dispensing tray to an incubation unit and / or from an incubation unit to a detection component.

[0121] The following describes the detection process of the coagulation analyzer 100 for determining the cause of decreased fibrinogen in the plasma of the blood sample to be tested, using different implementation methods.

[0122] In the first embodiment, the controller 130 is configured to execute an anomaly identification process based on the principle of parallel trials when detection information characterizing a decrease in fibrinogen in the plasma to be tested is acquired, specifically including the following steps:

[0123] To obtain detection information characterizing the decrease in fibrinogen in the plasma to be tested;

[0124] In response to the acquisition of the detection information:

[0125] The control sample preparation unit 110 mixes a first portion of the plasma to be tested with a diluent and thrombin reagent. Specifically, the control sample preparation unit 110 dilutes the first portion of the plasma to be tested with the diluent at a first dilution ratio, and then mixes the diluted first portion of the plasma with the thrombin reagent to prepare the first test sample.

[0126] The control detection unit 120 detects the first test sample to obtain the first solidification time of the first test sample.

[0127] The control sample preparation unit 110 mixes a second portion of the plasma to be tested with a diluent and thrombin reagent. Specifically, the control sample preparation unit dilutes the second portion of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and then mixes the diluted second portion of the plasma with the thrombin reagent to prepare the second assay sample.

[0128] The control detection unit 120 detects the second test sample to obtain the second solidification time of the second test sample, and

[0129] The cause of the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0130] In this first embodiment, when the controller 130 acquires detection information characterizing a decrease in fibrinogen in the plasma to be tested, it automatically triggers an anomaly identification process: the control sample preparation component 110 prepares a first test sample and a second test sample from the plasma to be tested, a diluent, and a thrombin reagent at different dilution ratios; the control detection component 120 detects the first test sample and the second test sample to obtain a first coagulation time and a second coagulation time, so that the cause of the decrease in fibrinogen in the plasma to be tested can be more accurately identified based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, especially whether the decrease in fibrinogen in the plasma to be tested is related to interfering substances (such as antithrombin IIa anticoagulants, HIL, etc.) in the plasma to be tested.

[0131] For example, based on the principle of parallel experiments, the relationship between the coagulation time and dilution ratio of the plasma to be tested can be obtained at least from the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. This relationship can be compared with a reference curve to determine the reason for the decrease in fibrinogen in the plasma to be tested.

[0132] In the embodiments of this application, in the field of coagulation analysis, parallel testing can be understood as determining whether the sample curve formed after the plasma to be tested is diluted at multiple points forms a straight line parallel to the reference curve.

[0133] It is understood here that, in the embodiments of this application, the phrase "based on the principle of parallel experiments" means based on the same or similar concept as the parallel experiments, rather than necessarily being exactly the same as the parallel experiments.

[0134] In some embodiments, a reference curve for the coagulation analyzer of this application embodiment can be established using the accompanying reference plasma in the following manner: The reference plasma is diluted with diluent at at least two different dilution ratios, particularly at least three different dilution ratios, using the coagulation analyzer of this application embodiment, and thrombin reagent is added to the diluted reference plasma to prepare a reference sample. Each reference sample is then tested based on the Clauss method to obtain the FIB coagulation time of each reference sample. The reference curve is then plotted in a coordinate system, where the horizontal axis is the dilution ratio and the vertical axis is the FIB coagulation time.

[0135] In some embodiments, the dilution ratios selected when establishing the reference curve include at least a first reference dilution ratio, a second reference dilution ratio, and a third reference dilution ratio, wherein the second reference dilution ratio is twice the first reference dilution ratio, and the third reference dilution ratio is twice the second reference dilution ratio. For example, depending on the default dilution ratio settings of different coagulation analyzers, the first, second, and third reference dilution ratios can be 1 / 20 (2x dilution relative to the default dilution ratio), 1 / 10 (default dilution ratio), and 1 / 5 (2x concentration relative to the default dilution ratio), respectively; or the first, second, and third reference dilution ratios can be 1 / 40 (2x dilution relative to the default dilution ratio), 1 / 20 (default dilution ratio), and 1 / 10 (2x concentration relative to the default dilution ratio), respectively; or the first, second, and third reference dilution ratios can be 2 / 1 (2x dilution relative to the default dilution ratio), 1 / 1 (default dilution ratio), and 1 / 2 (2x concentration relative to the default dilution ratio), respectively.

[0136] In some embodiments, when establishing a reference curve, the reference curve can be drawn manually or automatically by the coagulation analyzer.

[0137] In some embodiments, the reference curve is a straight line fitted in semi-logarithmic or double-logarithmic coordinates.

[0138] In some embodiments, the reference curve is stored in the controller's storage medium or in a memory communicatively connected to the controller. The controller's processor can retrieve the sample curve from the controller's storage medium or the memory communicatively connected to the controller.

[0139] In some embodiments, when reagent batch changes, instrument adjustments, or quality control failures occur in the coagulation analyzer, a new reference curve is established.

[0140] In some embodiments, the controller 130 may be configured to first control the sample preparation component 110 to prepare a first test sample, then control the detection component 120 to detect the first test sample, then first control the sample preparation component 110 to prepare a second test sample, and then control the detection component 120 to detect the second test sample.

[0141] For example, with Figure 2 Taking the coagulation analyzer shown as an example, the controller 130 can be configured to perform the following steps:

[0142] The sample needle of the control sample dispensing section 230 draws the first part of the plasma to be tested from the injection component 220 and discharges it into the first reaction cup located in the dispensing cup tray;

[0143] The diluent needle 252 of the control reagent dispensing section 250 draws diluent from the diluent tray 242 and discharges it into the first reaction cup so as to dilute the first portion of the plasma to be tested at the first dilution ratio;

[0144] The control transfer unit transfers the first reaction cup, which contains a mixture of the first portion of the test plasma and the diluent, to the incubation section for incubation.

[0145] After incubation is complete, the reagent needle 251 of the reagent dispensing section 250 draws thrombin reagent from the reagent tray 242 and discharges it into the incubated first reaction cup to prepare the first test sample.

[0146] The control transfer unit or incubation unit transfers the first reaction cup containing the first test sample to the detection unit 120 for detection to obtain the first solidification time;

[0147] The sample needle of the control sample dispensing section 230 draws a second portion of the plasma to be tested from the injection component 220 and discharges it into the second reaction cup located in the dispensing plate;

[0148] The diluent needle 252 of the control reagent dispensing section 250 draws diluent from the diluent tray 242 and discharges it into the second reaction cup so as to dilute the second part of the plasma to be tested at the second dilution ratio;

[0149] The control transfer unit transfers the second reaction cup, which contains the second portion of the test plasma and diluent, to the incubation section for incubation.

[0150] After incubation is complete, the reagent needle 251 of the reagent dispensing section 250 draws thrombin reagent from the reagent tray 242 and discharges it into the incubated second reaction cup to prepare the second test sample; and

[0151] The control transfer unit or incubation unit transfers the second reaction cup containing the second test sample to the detection unit 120 for detection to obtain the second solidification time.

[0152] In other embodiments, the controller 130 may also be configured to control the sample preparation component 110 to first prepare the first test sample and the second test sample respectively, and then control the detection component 120 to detect the first test sample and the second test sample respectively.

[0153] In some embodiments, the second dilution ratio is greater than the first dilution ratio, for example, the second dilution ratio is at least two times or at least four times the first dilution ratio.

[0154] In some alternative embodiments, the first dilution ratio is greater than the second dilution ratio, for example, the first dilution ratio is at least two times or at least four times the second dilution ratio.

[0155] In some embodiments, the first dilution ratio and the second dilution ratio are different from each other and are each selected from any value between 2 / 1 and 1 / 6, for example, from combinations of 2 / 1, 1 / 1, 1 / 2, and 1 / 4. For example, the first dilution ratio is 1 / 1 and the second dilution ratio is 2 / 1, or the first dilution ratio is 2 / 1 and the second dilution ratio is 1 / 1. As another example, the first dilution ratio is 1 / 2 and the second dilution ratio is 1 / 1 or 2 / 1, or the first dilution ratio is 1 / 1 or 2 / 1 and the second dilution ratio is 1 / 2.

[0156] Understandably, depending on the default dilution ratio settings of different coagulation analyzers, the first and second dilution ratios can also be other values.

[0157] In some embodiments, the dilution ratio used to obtain the reference curve includes at least one of a first dilution ratio and a second dilution ratio. That is, at least one of the first dilution ratio and the second dilution ratio is selected from the reference dilution ratio used to obtain the reference curve.

[0158] In some embodiments, the dilution ratio used to obtain the reference curve includes a first dilution ratio and a second dilution ratio. That is, both the first dilution ratio and the second dilution ratio are selected from the reference dilution ratio used to obtain the reference curve.

[0159] In some embodiments, a third test sample can be further prepared and tested to obtain a third coagulation time, so as to more accurately identify the cause of the decrease in fibrinogen in the test plasma. That is, the controller 130 is also configured to: in response to the acquisition of the detection information, control the sample preparation unit 110 to dilute a third portion of the test plasma with a diluent at a third dilution ratio different from the first dilution ratio and the second dilution ratio, and mix the diluted third portion of the test plasma with thrombin reagent to prepare a third test sample; and control the detection unit 120 to test the third test sample to obtain the third coagulation time of the third test sample. Accordingly, determining the cause of the decrease in fibrinogen in the test plasma based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve includes: determining the cause of the decrease in fibrinogen in the test plasma based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, the third coagulation time and the third dilution ratio, and the reference curve.

[0160] For example, based on the principle of parallel experiments, the relationship between the coagulation time and dilution ratio of the plasma to be tested is obtained according to the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the third coagulation time and the third dilution ratio. This relationship is then compared with a reference curve to more accurately determine the cause of the decrease in fibrinogen in the plasma to be tested.

[0161] Similarly Figure 2 Taking the coagulation analyzer shown as an example, the controller 130 can be configured to perform the following steps after the sample preparation component 110 prepares the first and second test samples:

[0162] The sample needle of the control sample dispensing section 230 draws the third part of the plasma to be tested from the injection component 220 and discharges it into the third reaction cup located in the dispensing plate;

[0163] The diluent needle 252 of the control reagent dispensing section 250 draws diluent from the diluent tray 242 and discharges it into the third reaction cup so as to dilute the third part of the plasma to be tested at the third dilution ratio;

[0164] The control transfer unit transfers the third reaction cup, which contains the third part of the test plasma and diluent, to the incubation section for incubation.

[0165] After incubation, the reagent needle 251 of the reagent dispensing unit 250 draws thrombin reagent from the reagent tray 242 and discharges it into the incubated third reaction cup to prepare the third test sample; and

[0166] The control transfer unit or incubation unit transfers the third reaction cup containing the third test sample to the detection unit 120 for detection to obtain the third solidification time.

[0167] In some embodiments, the third dilution ratio is greater than the second dilution ratio, for example, the third dilution ratio is at least two times or at least four times the second dilution ratio.

[0168] In other alternative embodiments, the second dilution ratio is greater than the third dilution ratio, for example, the second dilution ratio is at least two times or at least four times the third dilution ratio.

[0169] In some embodiments, the second dilution ratio and the third dilution ratio are different from each other and are each selected from any value between 2 / 1 and 1 / 6, for example, from combinations of 2 / 1, 1 / 1, 1 / 2, and 1 / 4, respectively. For example, the second dilution ratio is 1 / 1 and the third dilution ratio is 2 / 1, or the second dilution ratio is 2 / 1 and the third dilution ratio is 1 / 1. As another example, the second dilution ratio is 1 / 2 and the third dilution ratio is 1 / 1 or 2 / 1, or the second dilution ratio is 1 / 1 or 2 / 1 and the third dilution ratio is 1 / 2.

[0170] As some implementations, the first dilution ratio is 1 / 2, the second dilution ratio is 1 / 1, and the third dilution ratio is 2 / 1. Alternatively, the first dilution ratio is 2 / 1, the second dilution ratio is 1 / 1, and the third dilution ratio is 1 / 2.

[0171] In some other implementations, the first dilution ratio is 1 / 4, the second dilution ratio is 1 / 2, and the third dilution ratio is 1 / 1 or 2 / 1. Alternatively, the first dilution ratio is 1 / 1 or 2 / 1, the second dilution ratio is 1 / 2, and the third dilution ratio is 1 / 4.

[0172] In some other implementations, the first dilution ratio is 1 / 4, the second dilution ratio is 1 / 2 or 1 / 1, and the third dilution ratio is 2 / 1. Alternatively, the first dilution ratio is 2 / 1, the second dilution ratio is 1 / 2 or 1 / 1, and the third dilution ratio is 1 / 4.

[0173] Understandably, depending on the default dilution ratio settings of different coagulation analyzers, the first, second, and third dilution ratios can also be other values.

[0174] In some embodiments, the dilution ratio used to obtain the reference curve may include a third dilution ratio. In particular, the first dilution ratio, the second dilution ratio, and the third dilution ratio are all selected from the reference dilution ratio used to obtain the reference curve.

[0175] In this embodiment, the controller 130 can acquire detection information characterizing the decrease in fibrinogen in the plasma to be tested through different methods or pathways. For example, the detection information may include a detection value related to the fibrinogen concentration in the plasma to be tested being outside a preset range or may include user input information.

[0176] The detection value related to the fibrinogen concentration in the plasma to be tested may include at least one of the fibrinogen concentration obtained based on the Clauss method (hereinafter also referred to as the first fibrinogen concentration value) and the fibrinogen concentration obtained based on the algorithm (hereinafter also referred to as the second fibrinogen concentration value), or a parameter calculated therefrom, such as the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value.

[0177] In some embodiments, obtaining detection information characterizing the decrease in fibrinogen in the plasma to be tested may include: obtaining a first fibrinogen concentration value characterizing the fibrinogen activity in the plasma to be tested and obtaining detection information based on the first fibrinogen concentration value.

[0178] Furthermore, the detection information obtained based on the first fibrinogen concentration value may include, for example, the first fibrinogen concentration value being less than a first threshold.

[0179] As some implementation methods, fibrinogen concentration obtained based on the Clauss method, i.e., obtaining a first fibrinogen concentration value characterizing the fibrinogen activity in the plasma to be tested, may include:

[0180] The control sample preparation component 110 uses a diluent to dilute the fourth portion of the plasma to be tested at a fourth dilution ratio, and mixes the diluted fourth portion of the plasma to be tested with thrombin reagent to prepare the fourth test sample;

[0181] The control detection unit 120 detects the fourth test sample to obtain the fourth solidification time of the fourth test sample; and

[0182] The first fibrinogen concentration value was obtained based on the fourth coagulation time.

[0183] Here, the detection information includes a first fibrinogen concentration value that is less than a first threshold.

[0184] In other words, the coagulation analyzer first analyzes a portion of the plasma sample to be tested (i.e., the fourth portion mentioned above) using the Clauss method to obtain a first fibrinogen concentration value characterizing the fibrinogen activity in the plasma. When the first fibrinogen concentration value is less than a first threshold, an anomaly identification process based on the principle of parallel testing is automatically initiated. Optionally, the cause of the decrease in fibrinogen in the plasma can be further determined based on the fourth coagulation time and fourth dilution ratio obtained when the coagulation analyzer analyzes the portion of the plasma to be tested using the Clauss method. That is, the cause of the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and first dilution ratio, the second coagulation time and second dilution ratio, and the reference curve. This can include determining the cause of the decrease in fibrinogen in the plasma to be tested based on the first coagulation time and first dilution ratio, the second coagulation time and second dilution ratio, the fourth coagulation time and fourth dilution ratio, and the reference curve.

[0185] In some embodiments, the first dilution ratio, the second dilution ratio, and the fourth dilution ratio are different from each other and are each selected from any value between 2 / 1 and 1 / 6, for example, from combinations of 2 / 1, 1 / 1, 1 / 2, and 1 / 4, respectively.

[0186] In some embodiments, the dilution ratio used to obtain the reference curve may also include a fourth dilution ratio.

[0187] In some other implementations, the controller 130 can also acquire detection information based on the subject's historical first fibrinogen concentration value in the plasma to be tested.

[0188] In some other implementations, the controller 130 may also receive a first fibrinogen concentration value input by a user through a user interface, such as a user interface, and obtain detection information based on the received first fibrinogen concentration value.

[0189] In other embodiments, obtaining detection information characterizing a decrease in fibrinogen in the test plasma may include obtaining detection information characterizing that the test plasma originated from a subject suspected of having dysfibrinogenemia. That is, since dysfibrinogenemia is a cause of decreased fibrinogen, when it is suspected that the test plasma originated from a subject suspected of having dysfibrinogenemia, an anomaly identification process based on the principle of parallel trials can be automatically initiated to assist the user in more accurately determining whether the decreased fibrinogen is caused by dysfibrinogenemia.

[0190] As one implementation, when the detection component is constructed as a photometric component that measures the sample based on an optical method, a second fibrinogen concentration value reflecting the total amount of fibrinogen antigen in the plasma to be tested can be obtained based on an algorithm, and detection information characterizing that the plasma to be tested originates from a subject suspected of having abnormal fibrinogenemia can be obtained based on the second fibrinogen concentration value.

[0191] Specifically, obtaining testing information characterizing that the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia includes:

[0192] The control sample preparation unit 110 mixes the fifth part of the plasma to be tested with a preset detection reagent to prepare the fifth test sample, wherein the preset detection reagent is any one of the following reagents: PT assay reagent, TT assay reagent, APTT assay reagent, FIB assay reagent, LA assay reagent, and ECT assay reagent.

[0193] The photometric component is controlled to perform photometric measurements on the fifth test sample to obtain the change in luminous flux or absorbance of the transmitted or scattered light from the start of the solidification reaction to the end of the solidification reaction.

[0194] The second fibrinogen concentration value, which reflects the total amount of fibrinogen antigen in the plasma to be tested, is determined based on the change in light flux or the change in absorbance.

[0195] Here, the detection information includes a second fibrinogen concentration value that is less than a second threshold, or a ratio of the second fibrinogen concentration value to the first fibrinogen concentration value that is greater than a third threshold.

[0196] In some preferred examples, the preset detection reagent is a reagent for PT determination or a reagent for FIB determination, that is, the second fibrinogen concentration value is obtained based on the PT algorithm or the FIB algorithm.

[0197] In other implementations, the controller 130 may also receive a second fibrinogen concentration value input by a user through a user interface, such as a user interface, and obtain detection information based on the received second fibrinogen concentration value.

[0198] In some other implementations, the controller 130 may also receive user input via a user interface, such as a user interface, indicating that the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia.

[0199] In other embodiments, the controller 130 may also receive, via a user interface, such as a user interface, a user input instruction to trigger an anomaly identification process based on the principle of parallel trials. That is, the anomaly identification process can be manually initiated by the user. Optionally, the controller 130 may also receive, via user input, a first dilution ratio, a second dilution ratio, a third dilution ratio, etc. Furthermore, the controller 130 may also receive, via user input, judgment criteria, such as the degree of parallelism, as described below.

[0200] In some embodiments, the detection information may include a first fibrinogen concentration value that is less than a first threshold or a ratio of a second fibrinogen concentration value to a first fibrinogen concentration value that is greater than a third threshold.

[0201] The following describes some examples of determining the cause of decreased fibrinogen in the plasma being tested, as well as some countermeasures after determining the cause of decreased fibrinogen.

[0202] In some embodiments, determining the cause of the decrease in fibrinogen in the plasma to be tested, based at least on a first coagulation time and a first dilution ratio, a second coagulation time and a second dilution ratio, and a reference curve, may include:

[0203] Based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, determine whether the fibrinogen in the plasma to be tested is reduced due to interfering substances.

[0204] Furthermore, the controller 130 can be used to output a prompt message when it is determined that the fibrinogen level in the plasma to be tested has decreased due to interfering substances.

[0205] In some embodiments, determining the cause of decreased fibrinogen in the plasma sample, based at least on a first coagulation time and a first dilution ratio, a second coagulation time and a second dilution ratio, and a reference curve, may include:

[0206] Data fitting was performed based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio, to obtain a sample curve. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with a diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios and the different dilution ratios.

[0207] Determine whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decrease in fibrinogen in the plasma to be tested.

[0208] Here, the sample curve and the reference curve can be plotted on the same coordinate system, for example, to facilitate the identification of the relationship between the sample curve and the reference curve. In this same coordinate system, the horizontal axis represents the dilution ratio, and the vertical axis represents the solidification time.

[0209] Furthermore, the reference curve can be a straight line fitted in semi-logarithmic or double-logarithmic coordinates. Here, data fitting based on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, is performed to obtain the sample curve. This includes: performing linear data fitting based on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, in semi-logarithmic or double-logarithmic coordinates to obtain the sample curve. Accordingly, determining whether a predetermined relationship exists between the sample curve and the reference curve includes: determining whether the sample curve and the reference curve are parallel or approximately parallel.

[0210] In particular, the reference curve and the sample curve can be plotted in the same semi-logarithmic coordinate system or the same double-logarithmic coordinate system, where the horizontal axis represents the dilution ratio and the vertical axis represents the solidification time.

[0211] As can be understood here, "roughly parallel" means that the degree of parallelism is within a certain error range, such as allowing an error of ±20%, ±15%, ±10%, ±5%, etc.

[0212] In some examples, the slope, angle, and statistical parameters of the sample curve and the reference curve can be used to determine whether the sample curve and the reference curve are parallel or approximately parallel.

[0213] As some implementation methods, determining whether a sample curve is parallel or approximately parallel to a reference curve may include: if the slope of the sample curve is the same as the slope of the reference curve, or if the absolute difference between the slopes of the sample curve and the reference curve is less than a fourth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve.

[0214] For example, if the slope of the sample curve is Kc and the slope of the reference curve is Ks, then the absolute difference between the slopes of the sample curve and the reference curve is |Kc-Ks|. When |Kc-Ks| is less than the fourth threshold, for example, less than 0.3, less than 0.2, or less than 0.1, the sample curve is considered to be parallel or approximately parallel to the reference curve; otherwise, they are not parallel.

[0215] As other implementations, determining whether a sample curve is parallel or approximately parallel to a reference curve may include: if the sample curve and the reference curve do not intersect in the same coordinate system or the acute angle between the sample curve and the reference curve in the same coordinate system is less than the fifth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve.

[0216] As another implementation method, determining whether the sample curve and the reference curve are parallel or approximately parallel can include: if the linear correlation coefficient between the sample curve and the reference curve is greater than the sixth threshold, then the sample curve and the reference curve are determined to be parallel or approximately parallel.

[0217] As another implementation, determining whether the sample curve and the reference curve are parallel or approximately parallel may include: obtaining the first theoretical solidification time and the second theoretical solidification time from the reference curve based on the first dilution ratio and the second dilution ratio; and determining whether the sample curve and the reference curve are parallel or approximately parallel based on the difference between the first solidification time and the first theoretical solidification time and the difference between the second solidification time and the second theoretical solidification time.

[0218] In addition, the following method can be used to determine whether the sample curve and the reference curve are parallel or approximately parallel: Assume that the sample curve has N fitting points (N≥2 and are integers, corresponding to solidification times Si, i=1~N respectively); select the conversion dilution ratio as P1, map the solidification time S1 on the sample curve corresponding to the dilution ratio P1 to the corresponding solidification time C1 on the reference curve, with a conversion factor of K=C1 / S1, and the corresponding mapping point is S'; use the same factor K to perform the transformation on all other points on the sample curve to obtain the curve S', then the deviation of each point on S' relative to the corresponding point on the reference curve can be used to determine whether the sample curve and the reference curve are parallel or approximately parallel.

[0219] In some alternative embodiments, data fitting based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio, may not be necessary. For example, determining the cause of the decrease in fibrinogen in the plasma sample based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and a reference curve may include:

[0220] The first theoretical setting time and the second theoretical setting time were obtained from the reference curve based on the first dilution ratio and the second dilution ratio; and

[0221] The reasons for the decrease in fibrinogen in the plasma to be tested were determined based on the difference between the first coagulation time and the first theoretical coagulation time, and the difference between the second coagulation time and the second theoretical coagulation time.

[0222] In some embodiments, determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of decreased fibrinogen in the plasma to be tested includes:

[0223] When there is no preset relationship between the sample curve and the reference curve, for example, when the sample curve and the reference curve are not parallel, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to contain interfering substances or that the plasma to be tested is suspected to originate from a subject with acquired dysfibrinogenemia.

[0224] When there is a pre-defined relationship between the sample curve and the reference curve, such as when the sample curve is parallel or approximately parallel to the reference curve, the reason for the decrease in fibrinogen in the test plasma is suspected to be that the test plasma comes from a subject with hypofibrinogenemia or hereditary abnormal fibrinogenemia.

[0225] like Figures 3 to 7 As shown, an anomaly identification process is performed on five blood samples with different causes of decreased fibrinogen using a coagulation analyzer according to an embodiment of this application to obtain corresponding sample curves and reference curves. Three dilution ratios, namely 1 / 2, 1 / 1, and 2 / 1, are selected, with a preset parallel relationship. The slope is used to determine whether the sample curve is parallel or approximately parallel to the reference curve. The judgment parameter is the absolute difference between the slope of the sample curve and the slope of the reference curve, |Kc-Ks|. Here, the slope of the reference curve is Ks = -0.802, and the fourth threshold is 0.2. Therefore, when Kc is in the range of -0.602 to -1.00, the sample curve is considered to be parallel or approximately parallel to the reference curve; otherwise, it is not parallel.

[0226] Figure 3 The sample curve of a blood sample with hypofibrinogenemia (hypofibrinogenemia) is shown, where Kc = -0.826. It can be determined that the sample curve is parallel to the reference curve, indicating that there are no interfering substances in the blood sample.

[0227] Figure 4 The sample curve of a blood sample with jaundice interference is shown, where Kc=0.392. It can be determined that the sample curve is not parallel to the reference curve, indicating the presence of interfering substances in the blood sample.

[0228] Figure 5 The sample curve of a blood sample with hereditary abnormal fibrinogenemia is shown, where Kc = -0.751, which indicates that the sample curve is parallel to the reference curve, suggesting that there are no interfering substances in the blood sample.

[0229] Figure 6 The sample curve of a blood sample with acquired abnormal fibrinogenemia is shown, where Kc=0.446. It can be determined that the sample curve is not parallel to the reference curve, indicating the presence of interfering substances in the blood sample.

[0230] Figure 7The sample curve of a blood sample with resistance to IIa interference (argatroban) is shown, where Kc=0.468. It can be determined that the sample curve is not parallel to the reference curve, indicating the presence of interfering substances in the blood sample.

[0231] In addition, an anomaly identification process was performed on blood samples with anti-IIa interference (bivalirudin). The obtained sample curve had a Kc=0.432, which indicates that the sample curve is not parallel to the reference curve, indicating that there is interfering substance in the blood sample.

[0232] Furthermore, the cause of the decreased fibrinogen in the test plasma can be determined by considering whether the plasma was derived from a subject suspected of having abnormal fibrinogenemia. Therefore, in some embodiments, determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decreased fibrinogen in the test plasma may further include:

[0233] To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia;

[0234] When there is no predetermined relationship between the sample curve and the reference curve, such as they are not parallel and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested comes from a subject with acquired abnormal fibrinogenemia, and optionally, this is output as a prompt message.

[0235] When there is no preset relationship between the sample curve and the reference curve, such as they are not parallel and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be the presence of interfering substances in the plasma to be tested, and optionally, this is output as a prompt message.

[0236] When there is a preset relationship between the sample curve and the reference curve, such as parallel or approximately parallel, and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested comes from a subject with hereditary abnormal fibrinogenemia, and optionally, this is output as a prompt message.

[0237] When there is a preset relationship between the sample curve and the reference curve, such as parallel or approximately parallel, and the sample to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and optionally, this can be output as a prompt.

[0238] As one implementation method, the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value can be used to determine whether the plasma being tested originates from a subject suspected of having dysfibrinogenemia. For example, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is greater than a third threshold, it can be predicted that the plasma being tested originates from a subject suspected of having dysfibrinogenemia; conversely, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is not greater than the third threshold, it can be predicted that the plasma being tested does not originate from a subject suspected of having dysfibrinogenemia.

[0239] Figure 8 An exemplary flowchart is shown to analyze the reasons for decreased fibrinogen levels in the plasma being tested. In this example, the detection information includes a first fibrinogen concentration value less than a first threshold or a second fibrinogen concentration value in ratio to the first fibrinogen concentration value greater than a third threshold.

[0240] like Figure 8As shown, in step S810, the controller 130 determines whether the first fibrinogen concentration value F1 is less than the first threshold N1 or whether the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is greater than the third threshold N3. If the controller 130 determines that the first fibrinogen concentration value is not less than the first threshold and the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is not greater than the third threshold, then in step S820, the first fibrinogen concentration value is output and the process ends. If the controller 130 determines that the first fibrinogen concentration value is less than the first threshold or the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is greater than the third threshold, that is, the controller 130 has obtained the corresponding detection information, then in step S830, the anomaly identification process is started to obtain the sample curve. Next, in step S840, the controller 130 determines whether the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is greater than the third threshold N3. If the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is greater than the third threshold N3, then in step S850, the controller 130 determines whether the sample curve is parallel or approximately parallel to the reference curve. If the sample curve is parallel or approximately parallel to the reference curve, then the reason for the decrease in fibrinogen in the test plasma is that the test plasma is suspected to originate from a subject with hereditary dysfibrinogenemia. If the sample curve is not parallel to the reference curve, then the reason for the decrease in fibrinogen in the test plasma is that the test plasma is suspected to originate from a subject with acquired dysfibrinogenemia. If the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is not greater than the third threshold N3, then in step S860, the controller 130 determines whether the sample curve is parallel or approximately parallel to the reference curve. If the sample curve is parallel or approximately parallel to the reference curve, then the reason for the decrease in fibrinogen in the test plasma is that the test plasma is suspected to originate from a subject with hypofibrinogenemia. If the sample curve is not parallel to the reference curve, the reason for the decrease in fibrinogen in the test plasma is suspected to be the presence of interfering substances in the test plasma.

[0241] Figure 9 This diagram illustrates another exemplary flowchart for analyzing the reasons for decreased fibrinogen levels in the plasma being tested. Figure 9 The flowchart shown is Figure 8 The flowcharts shown are basically the same, the difference being: Figure 8 In the first step, it is determined whether the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is greater than the third threshold N3. Then, it is determined whether the sample curve and the reference curve are parallel or approximately parallel. Figure 9First, determine whether the sample curve is parallel or approximately parallel to the reference curve. Then, determine whether the ratio of the second fibrinogen concentration value F2 to the first fibrinogen concentration value F1 is greater than the third threshold N3.

[0242] In some embodiments, the controller 130 may also be configured to output a corresponding fibrinogen concentration value after determining the cause of the decrease in fibrinogen in the plasma to be tested:

[0243] When it is determined that the decrease in fibrinogen in the test plasma is due to the suspected origin of the test plasma from a subject with hypofibrinogenemia, the fibrinogen concentration value is output based on the coagulation time corresponding to the larger of the first, second, and third dilution ratios.

[0244] When it is determined that the decrease in fibrinogen in the test plasma is due to the suspected presence of interfering substances in the test plasma, the fibrinogen concentration value is output based on the coagulation time corresponding to the smallest dilution ratio among the first dilution ratio, the second dilution ratio, and the third dilution ratio.

[0245] When it is determined that the decrease in fibrinogen in the test plasma is due to the suspected origin of the test plasma from a subject with hereditary or acquired abnormal fibrinogenemia, a second fibrinogen concentration value is output.

[0246] For example, when the first dilution ratio is greater than the second dilution ratio and the second dilution ratio is greater than the third dilution ratio, the larger of the first dilution ratio, the second dilution ratio and the third dilution ratio is the first dilution ratio or the second dilution ratio, for example, 2 / 1 or 1 / 2, especially 2 / 1, and the smallest of the first dilution ratio, the second dilution ratio and the third dilution ratio is the third dilution ratio, for example, 1 / 4.

[0247] For example, when the first dilution ratio is less than the second dilution ratio and the second dilution ratio is less than the third dilution ratio, the larger of the first dilution ratio, the second dilution ratio and the third dilution ratio is the second dilution ratio or the third dilution ratio, for example, 2 / 1 or 1 / 2, especially 2 / 1, while the smallest of the first dilution ratio, the second dilution ratio and the third dilution ratio is the first dilution ratio, for example, 1 / 4.

[0248] In some embodiments, after determining the cause of decreased fibrinogen in the plasma to be tested according to the embodiments of this application, the user, such as a doctor, can provide targeted countermeasures.

[0249] For example, in samples suspected of having hereditary atypical fibrinogen, doctors can rule out the use of dextran or hydroxyethyl starch and conduct family studies or fibrinogen / gene analysis. In samples suspected of having acquired atypical fibrinogen, doctors can conduct family studies to rule out hereditary abnormal fibrinogenemia; after the condition improves, TT, reptilian enzyme time, F2 / F1 ratio, etc., should be tested again. In samples suspected of having hypofibrinogenemia, doctors should consult with clinicians to confirm whether fibrinolytic drugs such as batroxobin have been used and check for abnormal liver function indicators. In samples suspected of containing interfering substances, doctors can confirm the presence of jaundice, chyluria, hemolysis, etc., and whether the sample condition is normal; if necessary, blood can be drawn again, and the sample can be centrifuged at high speed.

[0250] The above is a description of the first embodiment and its various embodiments of this application. Next, the second embodiment of this application will be described.

[0251] In the second embodiment, the controller 130 is configured to:

[0252] Obtain the first fibrinogen concentration value of the plasma to be tested.

[0253] The presence of decreased fibrinogen in the tested plasma is determined based on the first fibrinogen concentration value.

[0254] If it is determined that there is no decrease in fibrinogen in the plasma to be tested, the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value.

[0255] If it is determined that the plasma to be tested has decreased fibrinogen, a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of the sample prepared by mixing the plasma to be tested with diluent and thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of the sample prepared by mixing the reference plasma with diluent and thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decreased fibrinogen in the plasma to be tested.

[0256] In some embodiments, the first fibrinogen concentration can be obtained by a coagulation analyzer based on the Clauss method, that is, obtaining the first fibrinogen concentration value of the plasma to be tested includes:

[0257] The control sample preparation component 110 uses a diluent to dilute the fourth portion of the plasma to be tested at a fourth dilution ratio, and mixes the diluted fourth portion of the plasma to be tested with thrombin reagent to prepare the fourth test sample;

[0258] The control detection unit 120 detects the fourth test sample to obtain the fourth solidification time of the fourth test sample; and

[0259] The first fibrinogen concentration value is obtained based on the fourth coagulation time, and the first fibrinogen concentration value characterizes the fibrinogen activity in the blood sample to be tested.

[0260] In some embodiments, obtaining a sample curve may include:

[0261] The control sample preparation component 110 uses a diluent to dilute a first portion of the plasma to be tested at a first dilution ratio, and mixes the diluted first portion of the plasma to be tested with thrombin reagent to prepare a first test sample, wherein the first dilution ratio is different from the fourth dilution ratio;

[0262] The control detection unit 120 detects the first test sample to obtain the first solidification time of the first test sample; and

[0263] The sample curve is determined at least based on the first setting time and the first dilution ratio, and the fourth setting time and the fourth dilution ratio.

[0264] In some alternative embodiments, obtaining the sample curve may include:

[0265] The control sample preparation component 110 uses a diluent to dilute a first portion of the plasma to be tested at a first dilution ratio, and mixes the diluted first portion of the plasma to be tested with thrombin reagent to prepare a first test sample;

[0266] The control detection component 120 detects the first test sample to obtain the first solidification time of the first test sample.

[0267] The control sample preparation component 110 uses a diluent to dilute a second portion of the plasma to be tested at a second dilution ratio, and mixes the diluted second portion of the plasma to be tested with thrombin reagent to prepare a second test sample, wherein the second dilution ratio is greater than the first dilution ratio;

[0268] The control detection unit 120 detects the second test sample to obtain the second solidification time of the second test sample; and

[0269] The sample curve is determined at least based on the first setting time and the first dilution ratio, the second setting time and the second dilution ratio, and optionally the fourth setting time and the fourth dilution ratio.

[0270] For further embodiments of the second implementation method, such as how to obtain the sample curve, how to obtain the reference curve, and how to determine whether a preset relationship exists between the sample curve and the reference curve, please refer to the above description of the first implementation method and its embodiments. That is to say, the first implementation method and its embodiments can all be applied to the second implementation method.

[0271] The above describes the second embodiment and its various embodiments of this application. Next, the third embodiment of this application will be described.

[0272] In the third embodiment, the controller 130 is configured to:

[0273] The control sample preparation component 110 uses a diluent to dilute a first portion of the plasma to be tested at a first dilution ratio, and mixes the diluted first portion of the plasma to be tested with thrombin reagent to prepare a first test sample;

[0274] The control detection component 120 detects the first test sample to obtain the first solidification time of the first test sample.

[0275] The control sample preparation component 110 uses a diluent to dilute a second portion of the plasma to be tested at a second dilution ratio different from the first dilution ratio, and mixes the diluted second portion of the plasma to be tested with the thrombin reagent to prepare a second test sample;

[0276] The control detection component 120 detects the second test sample to obtain the second solidification time of the second test sample.

[0277] The sample curve is determined at least based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. The sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with a diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios, and these different dilution ratios.

[0278] To determine whether there is a pre-defined relationship between the sample curve and the reference curve, in order to identify the reason for the decrease in fibrinogen in the plasma to be tested, the reference curve represents the relationship between the coagulation time of the sample prepared by diluting the reference plasma with diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios.

[0279] In some embodiments, determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of decreased fibrinogen in the plasma to be tested may include:

[0280] To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia;

[0281] When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested comes from a subject with acquired abnormal fibrinogenemia, and optionally this is output as a prompt message.

[0282] When there is no predetermined relationship between the sample curve and the reference curve and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be the presence of interfering substances in the plasma to be tested, and this can be optionally output as a prompting information.

[0283] When there is a preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to come from a subject with hereditary abnormal fibrinogenemia, and this can be output as a prompting information.

[0284] When there is a preset relationship between the sample curve and the reference curve, and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and this can be optionally output as a prompt.

[0285] In some embodiments, the reference curve is a straight line fitted in semi-logarithmic or double-logarithmic coordinates. Accordingly,

[0286] Determining a sample curve based at least on a first setting time and a first dilution ratio, and a second setting time and a second dilution ratio, includes: performing linear data fitting on a semi-logarithmic or double-logarithmic coordinate system based at least on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, to obtain a sample curve; and determining whether there is a preset relationship between the sample curve and the reference curve, including: determining whether the sample curve and the reference curve are parallel or approximately parallel.

[0287] In some embodiments, determining whether the sample curve and the reference curve are parallel or approximately parallel includes:

[0288] If the slope of the sample curve is the same as the slope of the reference curve, or if the absolute difference between the slopes of the sample curve and the reference curve is less than a fourth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or

[0289] If the sample curve and the reference curve do not intersect in the same coordinate system, or if the acute angle between the sample curve and the reference curve in the same coordinate system is less than the fifth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or

[0290] If the linear correlation coefficient between the sample curve and the reference curve is greater than the sixth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve.

[0291] For further embodiments of the third implementation method, such as how to obtain the sample curve, how to obtain the reference curve, and how to determine whether a preset relationship exists between the sample curve and the reference curve, please refer to the above description of the first implementation method and its embodiments. That is to say, the first implementation method and its embodiments can all be applied to the third implementation method.

[0292] This application also provides some methods for analyzing fibrinogen in blood samples.

[0293] like Figure 10 As shown, a method 100 for analyzing fibrinogen in a blood sample includes:

[0294] Step S1010: Determine whether there is a decrease in fibrinogen in the blood sample to be tested;

[0295] When a blood sample is found to have decreased fibrinogen levels, the following steps are performed:

[0296] Step S1020: Dilute the first portion of the plasma to be tested in the blood sample to be tested with a diluent at a first dilution ratio, and mix the diluted first portion of the plasma to be tested with thrombin reagent to prepare the first test sample;

[0297] Step S1030: Test the first test sample to obtain the first solidification time of the first test sample.

[0298] Step S1040: Dilute the second part of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and mix the diluted second part of the plasma to be tested with thrombin reagent to prepare the second test sample;

[0299] Step S1050: The second test sample is tested to obtain the second solidification time of the second test sample; and

[0300] Step S1060: Determine the cause of the decrease in fibrinogen in the plasma to be tested based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve. The reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0301] In some embodiments, step S1060 may include:

[0302] Data fitting was performed based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio, to obtain a sample curve. The sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with a diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios.

[0303] Determine whether there is a pre-defined relationship between the sample curve and the reference curve to identify the cause of the decrease in fibrinogen in the plasma being tested.

[0304] In some embodiments, determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of decreased fibrinogen in the plasma to be tested may include:

[0305] When there is no predetermined relationship between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the test plasma is determined to be the presence of interfering substances in the test plasma or the suspected origin of the test plasma from a subject with acquired dysfibrinogenemia.

[0306] When there is a pre-defined relationship between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the test plasma is that the test plasma is suspected to have come from a subject with hypofibrinogenemia or hereditary abnormal fibrinogenemia.

[0307] Furthermore, determining whether a pre-defined relationship exists between the sample curve and the reference curve to identify the cause of the decreased fibrinogen in the tested plasma may include:

[0308] To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia;

[0309] When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested comes from a subject with acquired abnormal fibrinogenemia, and optionally, this is output as a prompt message.

[0310] When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be the presence of interfering substances in the plasma to be tested, and optionally, this can be output as a prompt message.

[0311] When there is a preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested comes from a subject with hereditary abnormal fibrinogenemia, and optionally, this is output as a prompt message.

[0312] When there is a preset relationship between the sample curve and the reference curve, and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and optionally, this can be output as a prompt message.

[0313] like Figure 11 As shown, a method 1100 for analyzing fibrinogen in a blood sample includes:

[0314] Step S1110: Obtain the first fibrinogen concentration value of the plasma of the blood sample to be tested;

[0315] Step S1120: Determine whether there is a decrease in fibrinogen in the plasma to be tested based on the first fibrinogen concentration value;

[0316] Step S1130: If it is determined that there is no decrease in fibrinogen in the plasma to be tested, then the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value.

[0317] Step S1140: If it is determined that the plasma to be tested has an abnormal decrease in fibrinogen, then a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of the sample prepared by diluting the plasma to be tested with a diluent and mixing the diluted plasma with thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of the sample prepared by diluting the reference plasma with a diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested.

[0318] like Figure 12 As shown, a method 1300 for analyzing fibrinogen in a blood sample includes:

[0319] Step S1210: Obtain the plasma to be tested from the blood sample to be tested;

[0320] Step S1220: Dilute the first portion of the plasma to be tested with a diluent at a first dilution ratio, and mix the diluted first portion of the plasma to be tested with thrombin reagent to prepare the first test sample;

[0321] Step S1230: Test the first test sample to obtain the first solidification time of the first test sample.

[0322] Step S1240: Dilute the second part of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and mix the diluted second part of the plasma to be tested with thrombin reagent to prepare the second test sample;

[0323] Step S1250: The second test sample is tested to obtain the second solidification time of the second test sample.

[0324] Step S1260: Determine a sample curve based at least on a first coagulation time and a first dilution ratio, and a second coagulation time and a second dilution ratio. The sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with a diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios and the different dilution ratios.

[0325] Step S1270: Determine whether there is a preset relationship between the sample curve and the reference curve in order to determine the reason for the decrease in fibrinogen in the plasma to be tested. The reference curve represents the relationship between the coagulation time of the sample prepared by diluting the reference plasma with diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

[0326] For further embodiments of methods 1000, 1100, and 1200, such as how to obtain sample curves, how to obtain reference curves, and how to determine whether a preset relationship exists between sample curves and reference curves, please refer to the above description of the first embodiment and its embodiments. That is, the first embodiment and its embodiments can all be applied to methods 1000, 1100, and 1200.

[0327] This application also provides a clinical decision support system, including:

[0328] Non-transitory machine-readable memory that stores executable instructions; and

[0329] One or more processors are configured to execute the executable instructions to perform the following operations:

[0330] Obtain sample curves and reference curves. The sample curve represents the relationship between the coagulation time of a sample prepared by diluting the test plasma with a diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios and that different dilution ratios. The reference curve represents the relationship between the coagulation time of a sample prepared by diluting reference plasma with a diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and that different dilution ratios.

[0331] To determine whether a predetermined relationship exists between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the plasma being tested can be identified; and

[0332] Output the corresponding prompt message on the user interface based on the determined reason.

[0333] In some embodiments, the one or more processors are configured to execute the executable instructions to perform methods 1000, 1100, and 1200 and one of their embodiments.

[0334] The embodiments of this application have now been described in detail. To avoid obscuring the concept of this application, some details known in the art have not been described. Those skilled in the art can fully understand how to implement the technical solutions disclosed herein based on the above description.

[0335] Those skilled in the art will understand that embodiments of this application can be provided as methods, systems, or computer program products. Therefore, this application can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, this application can take the form of a computer program product embodied on one or more computer-usable non-transitory storage media (including, but not limited to, disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0336] This application is described with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of this application. It should be understood that the functions specified in one or more flows in the flowchart illustrations and / or one or more blocks in the block diagrams can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, generate functions for implementing the functions in the flowchart illustrations. Figure 1 One or more processes and / or boxes Figure 1 A device that provides the functions specified in one or more boxes.

[0337] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing device to function in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means, which are implemented in a process Figure 1 One or more processes and / or boxes Figure 1 The function specified in one or more boxes.

[0338] These computer program instructions may also be loaded onto a computer or other programmable data processing equipment to cause a series of operational steps to be performed on the computer or other programmable equipment to produce a computer-implemented process, thereby providing instructions that execute on the computer or other programmable equipment for implementing the process. Figure 1 One or more processes and / or boxes Figure 1 The steps of the function specified in one or more boxes.

[0339] While specific embodiments of this application have been described in detail by way of examples, those skilled in the art should understand that the above examples are for illustrative purposes only and are not intended to limit the scope of this application. Those skilled in the art should understand that modifications can be made to the above embodiments or equivalent substitutions can be made to some technical features without departing from the scope and spirit of this application. The scope of this application is defined by the appended claims.

Claims

1. A coagulation analyzer, comprising: The sample preparation component is designed to prepare a test sample using plasma from the blood sample to be tested and detection reagents. A detection component is configured to detect the test sample; The controller is configured to acquire detection information characterizing a decrease in fibrinogen in the plasma to be tested, and in response to the acquisition of the detection information: The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample. The detection component is controlled to detect the first test sample to obtain the first solidification time of the first test sample. The sample preparation component is controlled to dilute a second portion of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested is mixed with thrombin reagent to prepare a second test sample. The detection component is controlled to detect the second test sample to obtain the second solidification time of the second test sample, and The reason for the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

2. The coagulation analyzer according to claim 1, wherein, The controller is further configured to, in response to the acquisition of the detection information, control the sample preparation component to dilute a third portion of the plasma to be tested with a diluent at a third dilution ratio different from the first dilution ratio and the second dilution ratio, and mix the diluted third portion of the plasma to be tested with thrombin reagent to prepare a third test sample; and control the detection component to detect the third test sample to obtain the third coagulation time of the third test sample. The step of determining the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, includes: determining the cause of the decrease in fibrinogen in the plasma to be tested, based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, the third coagulation time and the third dilution ratio, and the reference curve.

3. The coagulation analyzer according to claim 1 or 2, wherein, The acquisition of detection information characterizing the decrease in fibrinogen in the plasma to be tested includes: Obtain a first fibrinogen concentration value characterizing the fibrinogen activity in the plasma to be tested, and obtain the detection information based on the first fibrinogen concentration value; Preferably, obtaining the first fibrinogen concentration value, which characterizes the fibrinogen activity in the plasma to be tested, includes: The sample preparation component is controlled to dilute the fourth portion of the plasma to be tested with a diluent at a fourth dilution ratio, and the diluted fourth portion of the plasma to be tested is mixed with thrombin reagent to prepare the fourth test sample; The detection component is controlled to detect the fourth test sample to obtain the fourth solidification time of the fourth test sample; and The first fibrinogen concentration value is obtained based on the fourth coagulation time. The detection information includes the fact that the first fibrinogen concentration value is less than a first threshold. Optionally, determining the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, includes: determining the cause of the decrease in fibrinogen in the plasma to be tested, based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, the fourth coagulation time and the fourth dilution ratio, and the reference curve.

4. The coagulation analyzer according to any one of claims 1 to 3, wherein, The detection component is configured to detect the sample based on any one of the following methods: optical method, magnetic bead method, electrochemical method, and microfluidic method. Preferably, the detection component is configured as a photometric component that measures the photometric value of the test sample based on an optical method.

5. The coagulation analyzer according to any one of claims 1 to 4, wherein, The acquisition of detection information characterizing the decrease in fibrinogen in the plasma to be tested includes: acquiring detection information characterizing that the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia; Preferably, the detection component is configured as a photometric component for measuring the sample using an optical method, and the acquisition of detection information characterizing that the plasma to be tested originates from a subject suspected of having abnormal fibrinogenemia includes: The sample preparation component is controlled to mix the fifth portion of the plasma to be tested with a preset detection reagent to prepare a fifth test sample. The preset detection reagent is any one of the following reagents: PT assay reagent, TT assay reagent, APTT assay reagent, FIB assay reagent, LA assay reagent, and ECT assay reagent. Preferably, the preset detection reagent is a PT assay reagent. The photometric component is controlled to perform photometric measurements on the fifth test sample to obtain the change in luminous flux or absorbance of the transmitted or scattered light from the start of the solidification reaction to the end of the solidification reaction. Based on the change in light flux or the change in absorbance, a second fibrinogen concentration value reflecting the total amount of fibrinogen antigen in the plasma to be tested is determined. The detection information includes the second fibrinogen concentration value being less than a second threshold, or the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value being greater than a third threshold.

6. The coagulation analyzer according to any one of claims 1 to 5, wherein, The determination of the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and a reference curve, includes: Based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, it is determined whether the fibrinogen in the plasma to be tested is reduced due to interfering substances. Preferably, if it is determined that the fibrinogen in the plasma to be tested is reduced due to interfering substances, a prompt message is output.

7. The coagulation analyzer according to any one of claims 1 to 6, wherein, The determination of the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and a reference curve, includes: Data fitting is performed based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio, to obtain a sample curve. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios. Determine whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decrease in fibrinogen in the plasma to be tested.

8. The coagulation analyzer according to claim 7, wherein, The step of determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested includes: When there is no preset relationship between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to contain interfering substances or that the plasma to be tested is suspected to originate from a subject with acquired dysfibrinogenemia. When the preset relationship exists between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to originate from a subject suffering from hypofibrinogenemia or hereditary abnormal fibrinogenemia.

9. The coagulation analyzer according to claim 8, wherein, The step of determining whether a preset relationship exists between the sample curve and the reference curve to determine the reason for the decrease in fibrinogen in the plasma to be tested also includes: To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia, preferably, the determination is based on the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value. When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, preferably, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is greater than the third threshold, it is determined that the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested comes from a subject with acquired abnormal fibrinogenemia, and optionally, it is output as a prompt message. When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, preferably, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is not greater than the third threshold, the reason for the decrease in fibrinogen in the plasma to be tested is that there is suspected interference in the plasma to be tested, and optionally, it is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, preferably, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is greater than the third threshold, it is determined that the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested comes from a subject with hereditary abnormal fibrinogenemia, and optionally, it is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the sample to be tested is not from a subject suspected of having abnormal fibrinogenemia, preferably, when the ratio of the second fibrinogen concentration value to the first fibrinogen concentration value is not greater than the third threshold, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and optionally, this is output as a prompt message.

10. The coagulation analyzer according to claim 9, wherein, The controller is also configured to: When it is determined that the decrease in fibrinogen in the plasma to be tested is due to the suspicion that the plasma to be tested originated from a subject with hypofibrinogenemia, a fibrinogen concentration value is output based on the coagulation time corresponding to the larger of the first dilution ratio, the second dilution ratio, and the third dilution ratio. Preferably, the larger of the first dilution ratio, the second dilution ratio, and the third dilution ratio is 2 / 1 or 1 / 2. When it is determined that the decrease in fibrinogen in the plasma to be tested is due to the suspected presence of interfering substances in the plasma to be tested, the fibrinogen concentration value is output based on the coagulation time corresponding to the smallest dilution ratio among the first dilution ratio, the second dilution ratio, and the third dilution ratio. Preferably, the smallest dilution ratio among the first dilution ratio, the second dilution ratio, and the third dilution ratio is 1 / 4. When it is determined that the decrease in fibrinogen in the plasma to be tested is due to the suspicion that the plasma to be tested originated from a subject with hereditary or acquired dysfibrinogenemia, the second fibrinogen concentration value is output.

11. The coagulation analyzer according to any one of claims 7 to 19, wherein, The reference curve is a straight line fitted in semi-logarithmic or double-logarithmic coordinates. The step of fitting data based on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, to obtain a sample curve includes: performing linear data fitting on a semi-logarithmic or double-logarithmic coordinate system based on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, to obtain the sample curve; and Determining whether there is a preset relationship between the sample curve and the reference curve includes: determining whether the sample curve and the reference curve are parallel or approximately parallel.

12. The coagulation analyzer according to claim 11, wherein, The step of determining whether the sample curve is parallel or approximately parallel to the reference curve includes: If the slope of the sample curve is the same as the slope of the reference curve, or the absolute difference between the slopes of the sample curve and the reference curve is less than a fourth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or If the sample curve and the reference curve do not intersect in the same coordinate system, or if the acute angle between the sample curve and the reference curve in the same coordinate system is less than the fifth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or If the linear correlation coefficient between the sample curve and the reference curve is greater than the sixth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve.

13. The coagulation analyzer according to any one of claims 1 to 11, wherein, The determination of the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and a reference curve, includes: The first theoretical setting time and the second theoretical setting time are obtained from the reference curve based on the first dilution ratio and the second dilution ratio; and Based on the difference between the first coagulation time and the first theoretical coagulation time, and the difference between the second coagulation time and the second theoretical coagulation time, the cause of the decrease in fibrinogen in the plasma to be tested is determined, especially whether the sample curve is parallel or approximately parallel to the reference curve.

14. The coagulation analyzer according to any one of claims 1 to 13, wherein, The first dilution ratio, the second dilution ratio, and optionally the third dilution ratio and the fourth dilution ratio are different from each other and are each selected from any value between 2 / 1 and 1 / 6, preferably from a combination of 2 / 1, 1 / 1, 1 / 2, and 1 / 4.

15. The coagulation analyzer according to any one of claims 1 to 14, wherein, The dilution ratio used to obtain the reference curve includes the first dilution ratio and / or the second dilution ratio, or, optionally, the third dilution ratio and / or the fourth dilution ratio.

16. A coagulation analyzer, comprising: The sample preparation component is designed to prepare a test sample using plasma from the blood sample to be tested and detection reagents. A detection component is configured to detect the test sample; Controller, settings for: Obtain the first fibrinogen concentration value of the plasma to be tested. Based on the first fibrinogen concentration value, it is determined whether the plasma to be tested has a decrease in fibrinogen. If it is determined that there is no decrease in fibrinogen in the plasma to be tested, then the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value; If it is determined that the plasma to be tested has decreased fibrinogen, a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of a sample prepared by diluting the plasma to be tested with a diluent and mixing the diluted plasma with thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of a sample prepared by diluting a reference plasma with the diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decreased fibrinogen in the plasma to be tested.

17. The coagulation analyzer according to claim 16, wherein, The process of obtaining the first fibrinogen concentration value of the plasma to be tested includes: The sample preparation component is controlled to dilute the fourth portion of the plasma to be tested with a diluent at a fourth dilution ratio, and the diluted fourth portion of the plasma to be tested is mixed with thrombin reagent to prepare the fourth test sample; The detection component is controlled to detect the fourth test sample to obtain the fourth solidification time of the fourth test sample; and The first fibrinogen concentration value is obtained based on the fourth coagulation time, and the first fibrinogen concentration value characterizes the fibrinogen activity in the blood sample to be tested.

18. The coagulation analyzer according to claim 17, wherein, The acquisition of the sample curve includes: The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample, wherein the first dilution ratio is different from the fourth dilution ratio; The detection component is controlled to detect the first test sample to obtain the first solidification time of the first test sample; and The sample curve is determined at least based on the first solidification time and the first dilution ratio, and the fourth solidification time and the fourth dilution ratio.

19. The coagulation analyzer according to claim 16 or 17, wherein, The acquisition of the sample curve includes: The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample; The detection component is controlled to detect the first test sample in order to obtain the first solidification time of the first test sample. The sample preparation component is controlled to dilute a second portion of the plasma to be tested with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested is mixed with thrombin reagent to prepare a second test sample; The detection component is controlled to detect the second test sample to obtain the second solidification time of the second test sample; and The sample curve is determined at least based on the first solidification time and the first dilution ratio, the second solidification time and the second dilution ratio, and optionally the fourth solidification time and the fourth dilution ratio.

20. A coagulation analyzer, comprising: The sample preparation component is designed to dilute the plasma to be tested in the blood sample and mix the diluted plasma with the test reagent to prepare the test sample. A detection component is configured to detect the test sample; Controller, settings for: The sample preparation component is controlled to dilute a first portion of the plasma to be tested with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample. The detection component is controlled to detect the first test sample to obtain the first solidification time of the first test sample. The sample preparation component is controlled to dilute a second portion of the plasma to be tested with the diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested is mixed with the thrombin reagent to prepare a second assay sample. The detection component is controlled to detect the second test sample to obtain the second solidification time of the second test sample. A sample curve is determined at least based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios. To determine whether there is a preset relationship between the sample curve and the reference curve, in order to determine the reason for the decrease in fibrinogen in the plasma to be tested, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

21. The coagulation analyzer according to claim 20, wherein, The step of determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested includes: To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia; When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to come from a subject with acquired abnormal fibrinogenemia, and optionally this is output as a prompt message. When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be the presence of interfering substances in the plasma to be tested, and optionally, this is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested comes from a subject with hereditary abnormal fibrinogenemia, and optionally this is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and this can be output as a prompt message.

22. The coagulation analyzer according to claim 20 or 21, wherein, The reference curve is a straight line fitted in semi-logarithmic or double-logarithmic coordinates; Determining the sample curve based at least on the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, includes: performing linear data fitting on at least the first setting time and the first dilution ratio, and the second setting time and the second dilution ratio, in a semi-logarithmic or double-logarithmic coordinate system to obtain the sample curve; and Determining whether there is a preset relationship between the sample curve and the reference curve includes: determining whether the sample curve and the reference curve are parallel or approximately parallel.

23. The coagulation analyzer according to claim 22, wherein, The step of determining whether the sample curve is parallel or approximately parallel to the reference curve includes: If the slope of the sample curve is the same as the slope of the reference curve, or the absolute difference between the slopes of the sample curve and the reference curve is less than a fourth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or If the sample curve and the reference curve do not intersect in the same coordinate system, or if the acute angle between the sample curve and the reference curve in the same coordinate system is less than the fifth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve; or If the linear correlation coefficient between the sample curve and the reference curve is greater than the sixth threshold, then the sample curve is determined to be parallel or approximately parallel to the reference curve.

24. A method for analyzing fibrinogen in a blood sample, comprising: Determine whether the blood sample to be tested has a decrease in fibrinogen; When it is determined that the blood sample to be tested has decreased fibrinogen, the following steps are performed: The first portion of the plasma to be tested in the blood sample to be tested is diluted with a diluent at a first dilution ratio, and the diluted first portion of plasma to be tested is mixed with thrombin reagent to prepare a first test sample. The first test sample is tested to obtain the first solidification time of the first test sample. The second portion of the plasma to be tested was diluted with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested was mixed with thrombin reagent to prepare a second test sample; The second test sample is tested to obtain the second solidification time of the second test sample; and The reason for the decrease in fibrinogen in the plasma to be tested is determined at least based on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and the reference curve, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

25. The method according to claim 24, wherein, The determination of the cause of the decrease in fibrinogen in the plasma to be tested, based at least on the first coagulation time and the first dilution ratio, the second coagulation time and the second dilution ratio, and a reference curve, includes: Data fitting is performed based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio, to obtain a sample curve. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios. Determine whether there is a preset relationship between the sample curve and the reference curve to determine the reason for the decrease in fibrinogen in the plasma to be tested.

26. The method of claim 25, wherein, Determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decreased fibrinogen in the plasma to be tested includes: When there is no preset relationship between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to contain interfering substances or that the plasma to be tested is suspected to originate from a subject with acquired dysfibrinogenemia. When the preset relationship exists between the sample curve and the reference curve, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to originate from a subject suffering from hypofibrinogenemia or hereditary abnormal fibrinogenemia.

27. The method according to claim 26, wherein, Determining whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested also includes: To determine whether the plasma to be tested originated from a subject suspected of having abnormal fibrinogenemia; When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is that the plasma to be tested is suspected to come from a subject with acquired abnormal fibrinogenemia, and optionally, this is output as a prompt message. When there is no preset relationship between the sample curve and the reference curve and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be the presence of interfering substances in the plasma to be tested, and optionally, this is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the plasma to be tested comes from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested comes from a subject with hereditary abnormal fibrinogenemia, and optionally, this is output as a prompt message. When the preset relationship exists between the sample curve and the reference curve, and the plasma to be tested is not from a subject suspected of having abnormal fibrinogenemia, the reason for the decrease in fibrinogen in the plasma to be tested is determined to be that the plasma to be tested is suspected to be from a subject with hypofibrinogenemia, and optionally, this is output as a prompt message.

28. A method for analyzing fibrinogen in a blood sample, comprising: Obtain the first fibrinogen concentration value of the plasma in the blood sample to be tested; Based on the first fibrinogen concentration value, it is determined whether the plasma to be tested has a decrease in fibrinogen; If it is determined that there is no decrease in fibrinogen in the plasma to be tested, then the fibrinogen concentration value of the plasma to be tested is determined based on the first fibrinogen concentration value; If it is determined that the plasma to be tested has an abnormal decrease in fibrinogen, a sample curve and a reference curve are obtained. The sample curve represents the relationship between the coagulation time of a sample prepared by diluting the plasma to be tested with a diluent and mixing the diluted plasma with thrombin reagent at different dilution ratios and the different dilution ratios. The reference curve represents the relationship between the coagulation time of a sample prepared by diluting a reference plasma with the diluent and mixing the diluted reference plasma with thrombin reagent at different dilution ratios and the different dilution ratios. It is determined whether there is a preset relationship between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested.

29. A method for analyzing fibrinogen in a blood sample, comprising: Obtain plasma from the blood sample to be tested; The first portion of the plasma to be tested is diluted with a diluent at a first dilution ratio, and the diluted first portion of the plasma to be tested is mixed with thrombin reagent to prepare a first test sample; The first test sample is tested to obtain the first solidification time of the first test sample. The second portion of the plasma to be tested was diluted with a diluent at a second dilution ratio different from the first dilution ratio, and the diluted second portion of the plasma to be tested was mixed with thrombin reagent to prepare a second test sample; The second test sample is tested to obtain the second solidification time of the second test sample; A sample curve is determined at least based on the first coagulation time and the first dilution ratio, and the second coagulation time and the second dilution ratio. This sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with the thrombin reagent at different dilution ratios, and the different dilution ratios. To determine whether there is a preset relationship between the sample curve and the reference curve, in order to determine the reason for the decrease in fibrinogen in the plasma to be tested, wherein the reference curve characterizes the relationship between the coagulation time of the sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios.

30. A clinical decision support system, comprising: Non-transitory machine-readable memory that stores executable instructions; and One or more processors are configured to execute the executable instructions to perform the following operations: Obtain a sample curve and a reference curve, wherein the sample curve characterizes the relationship between the coagulation time of a sample prepared by diluting the test plasma with the diluent and mixing the diluted test plasma with thrombin reagent at different dilution ratios and the different dilution ratios; and the reference curve characterizes the relationship between the coagulation time of a sample prepared by diluting the reference plasma with the diluent and mixing the diluted reference plasma with the thrombin reagent at different dilution ratios and the different dilution ratios. Determine whether a predetermined relationship exists between the sample curve and the reference curve to determine the cause of the decrease in fibrinogen in the plasma to be tested; and Output the corresponding prompt message on the user interface based on the determined reason.

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