Blood coagulation index detection system and method based on ultrasonic guided waves

Abstract

The invention discloses a blood coagulation index detection system and method based on ultrasonic guided waves, and the method comprises the steps: calculating a blood coagulation index corresponding to a sample according to an obtained viscoelasticity change curve; comprising the following steps: the clot starting time is defined as the time interval from the time when a blood sample is placed in a blood clot index detection system to the time when initial fibrin starts to form, and the R time of a TEG detection result of a gold standard method is marked; the clot stabilization time is defined as the clot formation time of the blood sample and the K time of the TEG detection result of the gold standard method; the theta angle is used for measuring the generation and cross-linking speed of fibrin and the alpha angle of a TEG detection result of a gold standard method; the maximum clot strength is the MA value of the TEG detection result of the gold standard method. Compared with a TEG method, the method has the advantages that the detection time of blood coagulation indexes is remarkably shortened, time guarantee is provided for emergency blood coagulation function evaluation and reasonable application of blood products in an operation, and improvement of clinical prognosis is facilitated.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of hemostasis detection methods, in particular to a coagulation index detection system and method based on ultrasonic guided waves. BACKGROUND

[0002] Perioperative bleeding is one of the common complications of surgery, and its management usually relies on the infusion of allogeneic blood products. However, studies have shown that excessive or delayed infusion can lead to adverse outcomes such as infection, thrombosis and organ failure. Therefore, accurate and immediate coagulation function assessment is crucial for optimizing perioperative bleeding management. Viscoelastic hemostatic assays (VHAs) can comprehensively evaluate the blood coagulation process, but have limitations such as long time consumption, large sample size requirement, poor anti-interference ability, and are difficult to meet the needs of bedside real-time detection.

[0003] Clinical commonly used coagulation detection (such as PT, APTT, FIB, etc.) and fibrinolysis detection (such as D-dimer, FDP) mainly rely on optical turbidity method, chemical colorimetry or immunoassay. These technologies require separation of plasma, rely on reagents, and are complicated to operate, and cannot monitor the whole process of coagulation dynamically in real time. The existing technology has the following defects: (1) complex sample processing: centrifugation is required to obtain plasma, which is time-consuming and susceptible to interference (such as hemolysis, lipemia); (2) single parameter detection: most devices can only measure coagulation time or a single fibrinolysis indicator, making it difficult to comprehensively evaluate the dynamic balance of coagulation-fibrinolysis; (3) poor real-time performance: unable to capture the continuous process of coagulation initiation, fibrin formation and dissolution. Ultrasonic guided waves refer to mechanical waves propagating in solids or liquids, whose propagation characteristics (such as speed, attenuation, dispersion) are affected by the physical properties of the medium. In blood detection, ultrasound can reflect changes in blood viscoelasticity through acoustic impedance changes; coagulation phase in blood detection: from platelet activation to fibrin cross-linking, blood viscoelasticity gradually increases, resulting in an increase in ultrasonic guided wave propagation speed and a decrease in attenuation; fibrinolysis phase in blood detection: fibrinolysin degrades fibrin, and the clot structure is loose, resulting in changes in the dispersion characteristics of guided waves and signal energy attenuation.

[0004] Therefore, a coagulation index detection system and method based on ultrasonic guided waves are proposed to solve the difficulties existing in the prior art. SUMMARY

[0005] The purpose of the present application is to provide a coagulation index detection system and method based on ultrasonic guided waves, which realizes real-time monitoring of the viscoelasticity changes in the coagulation process and provides a new detection scheme for coagulation function assessment.

[0006] To achieve the above-mentioned purpose, the present application provides the following solutions:

[0007] A coagulation index detection system based on ultrasonic guided waves, comprising:

[0008] An ultrasonic guided wave excitation and detection module, comprising a permanent magnet, a coil and a magnetostrictive capillary; wherein the magnetostrictive capillary is filled with a blood sample after adding a blood coagulation reagent, the coil is wound on the magnetostrictive capillary, and the permanent magnet is used to provide a static magnetic field; the ultrasonic guided wave excitation and detection module excites and detects ultrasonic guided waves through the magnetostrictive effect and inverse magnetostrictive effect, and obtains the attenuation of the ultrasonic guided waves;

[0009] A data acquisition and storage module connected with the ultrasonic guided wave excitation and detection module, used for acquiring and storing the data output by the ultrasonic guided wave excitation and detection module, and uploading to the main controller;

[0010] A temperature control module for maintaining a constant temperature of the detection environment;

[0011] A main controller as the core of the system, used for calculating the viscoelasticity change of the blood sample through the attenuation of the ultrasonic guided waves, obtaining the blood coagulation index through real-time signal processing and data analysis, and displaying the detection results.

[0012] Preferably, the working principle of the ultrasonic guided wave excitation and detection module is as follows:

[0013] The ultrasonic guided wave is excited by the magnetostrictive effect: under the static magnetic field, the magnetostrictive capillary produces ultrasonic guided waves under the action of the dynamic magnetic field of the coil; the ultrasonic guided waves are detected as induced voltage by the coil through the inverse magnetostrictive effect when propagating; when the magnetostrictive capillary is filled with blood, the amplitude attenuation of the ultrasonic guided wave propagation changes with the viscosity of the blood, and the attenuation of the ultrasonic guided wave is obtained.

[0014] Preferably, the working principle of the main controller is as follows:

[0015] According to the hysteresis model of viscoelastic materials, the complex wave number is derived from the attenuation and the real wavelength of the ultrasonic guided wave; the complex wave velocity V is calculated, and the loss modulus E is calculated, so as to obtain the blood coagulation characteristic curve, and realize the quantitative representation of the viscosity change of the blood sample in the blood coagulation and fibrinolysis process.

[0016] A blood coagulation index detection method based on ultrasonic guided waves, applied to any one of the blood coagulation index detection systems based on ultrasonic guided waves, comprising the following steps:

[0017] S1, collecting a blood sample and preparing a blood sample to be detected;

[0018] S2, injecting the prepared blood sample into the magnetostrictive capillary and applying an ultrasonic guided wave excitation signal;

[0019] S3, real-time monitoring of the ultrasonic guided wave attenuation change of the magnetostrictive capillary, calculating the viscoelasticity change of the blood sample, and drawing a viscoelasticity change curve;

[0020] S4, after obtaining the viscoelasticity change curve, a coagulation index of the sample is calculated;

[0021] S5, outputting the detection result for evaluating the coagulation function and fibrinolysis state.

[0022] Preferably, in S4, the coagulation index of the sample calculated is used for evaluating the indexes of the TEG detection result of the gold standard method, including:

[0023] CIT (Clotting Initiation Time), defined as the time interval from the blood sample being placed into the coagulation index detection system to the initial fibrin starting to form, which reflects the enzymatic reaction stage in the coagulation process, and is used for evaluating the R time of the TEG detection result of the gold standard method; CIT is determined by the first derivative of the coagulation characteristic curve;

[0024] CST (Clotting Stability Time), defined as the time for the blood sample to form a clot, which reflects the kinetics of clot formation in the coagulation process, and is used for evaluating the K time of the TEG detection result of the gold standard method; CST is determined by the coagulation characteristic curve;

[0025] Angle θ, used for measuring the speed of fibrin production and cross-linking, and reflecting the fibrinogen content in the blood sample, and is used for evaluating the alpha angle of the TEG detection result of the gold standard method; θ is defined as the maximum included angle formed in the rising stage of the coagulation characteristic curve;

[0026] MCF (Maximum Clot Firmness), used for characterizing the dynamic characteristic peak value of the fibrin combining with the platelet under the mediation of the platelet glycoprotein GPIIb / IIIa, which represents the maximum strength of the fibrin clot, and is used for evaluating the MA value of the TEG detection result of the gold standard method; MA is defined as the dissipation modulus value corresponding to the 20% of the maximum value of the first derivative of the coagulation characteristic curve when the first derivative decreases.

[0027] The application further provides a non-transitory computer-readable storage medium having a computer program stored thereon, and the computer program is executed by a processor to implement the coagulation index detection method based on ultrasonic guided waves according to any one of the above.

[0028] According to the specific embodiments of the application, the following technical effects are achieved:

[0029] (1) The application provides a coagulation index detection method based on ultrasonic guided waves, which elaborates the corresponding relationship between the detection characteristic curve and the clot formation and dissolution process from a microscopic perspective. The method realizes real-time monitoring of the viscoelasticity change in the coagulation process by applying the ultrasonic guided wave technology, and provides a new detection scheme for coagulation function evaluation.

[0030] (2) The method has a detection speed significantly better than that of the traditional TEG method, greatly shortens the output time of the detection result, and is particularly crucial for the treatment of a clinical acute bleeding patient; the rapid diagnosis capability provides valuable decision basis for doctors in a time-sensitive treatment scenario (such as massive hemorrhage, intraoperative management and trauma rescue), is used for quickly identifying the best time point of treatment intervention, and evaluating the treatment effect in real time, so that the patient management is optimized, and the treatment efficiency is improved. The method has excellent diagnosis performance in the diagnosis of coagulation function abnormalities, and has high sensitivity and specificity. BRIEF DESCRIPTION OF DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0032] Figure 1 A structure diagram of a coagulation index detection system based on ultrasonic guided waves is provided for the present application.

[0033] Figure 2 A specific structure diagram of an ultrasonic guided wave excitation and detection module is provided for the present application.

[0034] Among them, 1 is a permanent magnet, 2 is a coil, and 3 is a magnetostrictive capillary.

[0035] Figure 3 A flow chart of the coagulation index detection method based on ultrasonic guided waves is provided for the present application.

[0036] Figure 4 A coagulation index setting diagram of the method is provided for the present application.

[0037] Figure 5 A scatter plot of the method parameters and the corresponding parameters of TEG is provided for the present application.

[0038] Among them, (A) is a scatter plot of TEG R and CIT of the method, (B) is a scatter plot of TEG K and CST of the method, (C) is a scatter plot of TEG alpha angle and theta angle of the method, and (D) is a scatter plot of TEG MA and MCF of the method.

[0039] Figure 6 A scatter plot of the method parameters after conversion and the corresponding parameters of TEG is provided for the present application.

[0040] Among them, (A) is a scatter plot of TEG alpha angle and log2(theta angle of the method), and (B) is a scatter plot of TEG MA and log2(MCF of the method).

[0041] Figure 7 Consistency analysis of the corrected method parameters of the present application and TEG parameters (Bland-Altman plot);

[0042] (A) Consistency analysis plot of TEGR and the CIT_pred method of the present application, (B) Consistency analysis plot of TEG K and the CST_pred method of the present application, (C) Consistency analysis plot of TEG alpha angle and the thetaAngle_pred method of the present application, (D) Consistency analysis plot of TEG MA and the MCF_pred method of the present application; DETAILED DESCRIPTION

[0043] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0044] In order to make the above objectives, characteristics and advantages of the present application more obvious and easy to understand, the present application will be further described in detail below with reference to the drawings and specific embodiments.

[0045] Embodiment 1

[0046] As shown in the above Figure 1 The present application provides an ultrasonic guided wave-based coagulation indicator detection system, which comprises:

[0047] An ultrasonic guided wave excitation and detection module, comprising a permanent magnet 1, a coil 2 and a magnetostrictive capillary 3; wherein the magnetostrictive capillary 3 is filled with a blood sample after adding a coagulation reagent, the coil 2 is wound on the magnetostrictive capillary 3, and the permanent magnet 1 is used to provide a static magnetic field; the ultrasonic guided wave excitation and detection module excites and detects ultrasonic guided waves through magnetostrictive effect and inverse magnetostrictive effect to obtain an ultrasonic guided wave attenuation amount; the magnetostrictive capillary serves as a waveguide medium for propagating ultrasonic guided waves;

[0048] A data acquisition and storage module, connected with the ultrasonic guided wave excitation and detection module, for acquiring and storing the data output by the ultrasonic guided wave excitation and detection module and uploading to a main controller;

[0049] A temperature control module for maintaining a constant temperature of the detection environment;

[0050] A main controller, as the core of the system, for calculating the viscoelasticity change of the blood sample through the ultrasonic guided wave attenuation amount, obtaining coagulation indicators through real-time signal processing and data analysis, and displaying the detection results.

[0051] The power management module is further included for providing power supply for the system.

[0052] Further, as shown in Fig. 1, in the ultrasonic guided wave excitation and detection module, the permanent magnet 1 is used to provide a static magnetic field, so that the magnetostrictive capillary 3 is in a magnetostrictive sensitive state; the coil 2 is used to generate a dynamic magnetic field after passing through an alternating current, and the dynamic magnetic field acts on the magnetostrictive capillary 3 to generate magnetostriction, thereby generating an ultrasonic guided wave. Figure 2

[0053] Further, the working principle of the ultrasonic guided wave excitation and detection module is as follows:

[0054] The guided wave is excited and detected through the magnetostrictive effect and the inverse magnetostrictive effect; in the presence of a static magnetic field, when the magnetostrictive capillary 3 is subjected to the dynamic magnetic field generated by the coil 2, magnetostriction occurs, thereby generating an ultrasonic guided wave; the magnetostrictive capillary 3 is used as a waveguide to guide the propagation of the ultrasonic guided wave; at the same time, the wave propagation causes the magnetostrictive capillary to deform, and an alternating magnetic field is generated based on the inverse magnetostrictive effect; according to Faraday's law of electromagnetic induction, the alternating magnetic field is detected by the coil and converted into an induced voltage;

[0055] When the magnetostrictive capillary 3 is filled with a blood sample, the ultrasonic guided wave will be excited and propagated on the magnetostrictive capillary 3; as the viscosity in the magnetostrictive capillary changes, the amplitude of the ultrasonic guided wave will attenuate during propagation at both ends of the magnetostrictive capillary, and the attenuation of the ultrasonic guided wave is obtained.

[0056] Due to the good anti-interference ability of the device, it can be applied to the bedside of a patient, so that the collection of a blood sample to the filling of the device can be completed in just three minutes. Thereafter, the operator only needs to add a coagulation reagent (about 2 minutes), and the detection can be started. The method and device described in the present application can complete the collection of all results in 30 minutes in a clinical environment, and the operation process is simplified and user-friendly, which shortens the time from sampling to result reporting from about 60 minutes of the traditional TEG method to about 35 minutes in the present embodiment.

[0057] Further, the temperature control module realizes temperature control through a PID controller, and the PID controller is composed of a proportional controller, an integral controller and a differential controller, and the formula is as follows:

[0058]

[0059] wherein Kp, Ki and Kd are gain coefficients of the proportional controller, the integral controller and the differential controller. p i d

[0060] ​​​​Further, the working principle of the main controller is as follows:

[0061] According to the hysteresis model of the viscoelastic material, the complex wave number is derived from the attenuation amount and the real wave length of the ultrasonic guided wave; thereby the complex wave velocity V is calculated, the loss modulus E is calculated, the coagulation characteristic curve is obtained, and the quantitative representation of the viscosity change of the blood sample in the coagulation and fibrinolysis processes is realized;

[0062] For the longitudinal vibration mode, the relationship between the loss modulus E and the complex wave velocity V is as follows:

[0063] E = pV 2

[0064] For the shear vibration mode, the relationship between the loss modulus E and the complex wave velocity V is as follows:

[0065] E = 2(1 + v)pV 2

[0066] Wherein, p is the strip density, and v is the Poisson's ratio of the strip.

[0067] Embodiment 2

[0068] As shown in Figure 3 A coagulation index detection method based on ultrasonic guided waves, applied to the coagulation index detection system based on ultrasonic guided waves of any one of the above, comprising the following steps:

[0069] S1, collecting a blood sample and preparing a blood sample to be detected;

[0070] S2, injecting the prepared blood sample into the magnetostrictive capillary 3, and applying an ultrasonic guided wave excitation signal;

[0071] S3, real-time monitoring of the ultrasonic guided wave attenuation change of the magnetostrictive capillary 3, calculating the viscoelasticity change of the blood sample, and drawing a viscoelasticity change curve;

[0072] S4, after obtaining the viscoelasticity change curve, the corresponding coagulation index of the sample is calculated;

[0073] S5, outputting the detection result, which is used for evaluating the coagulation function and the fibrinolysis state.

[0074] Further, in S4, the coagulation index of the sample calculated is used to evaluate the indexes of the TEG detection result of the gold standard method, including:

[0075] The four coagulation index calculation methods in the method are as shown in Figure 4 Specifically, the four coagulation indexes are used to represent the formation process of the blood clot in the coagulation process:

[0076] The first coagulation index is the clot initiation time (CIT), which is defined as the time interval from the time the blood sample is placed in the system of the present invention to the time when the initial fibrin begins to form. This index can reflect the key enzymatic reaction stage in the coagulation process and can be compared with the R time of the gold standard method TEG test results. Figure 4 As shown, CIT is determined by the first derivative of the coagulation characteristic curve, and the time point corresponding to when the rising phase of the first derivative of the coagulation characteristic curve reaches 20% of its maximum value is the CIT measurement value.

[0077] The second coagulation index is clot stabilization time (CST). CST is defined as the time required for a blood sample to form a clot of a certain strength, reflecting the dynamic process of clot formation during coagulation, and is comparable to the K time of the gold standard method TEG test results. Figure 4 As shown, CST is determined by the coagulation characteristic curve, and the time required for the coagulation characteristic curve to rise from the beginning to 0.2 is the CST measurement value.

[0078] The third coagulation index is angle (θ), which is used to measure the speed of fibrin formation and cross-linking (i.e., the clot strengthening stage). It can effectively reflect the fibrinogen content in the blood sample and compare with the α angle of the gold standard method TEG test results. Figure 4 As shown in Figure 3, θ is defined as the maximum angle formed in the rising phase of the coagulation characteristic curve, which can quantitatively characterize the dynamic formation rate and structural strength development process of the fibrin clot.

[0079] The fourth coagulation index is maximum clot firmness (MCF). MCF is used to characterize the peak value of the dynamic characteristics of fibrin binding to platelets mediated by platelet glycoprotein GPIIb / IIIa. This index not only represents the maximum strength that a fibrin clot can achieve, but also intuitively reflects the functional state and aggregation degree of platelets, and is comparable to the MA value of the gold standard method TEG test results. Figure 4 As shown in FIG, MA is defined as the dissipation modulus value corresponding to the first derivative of the coagulation characteristic curve dropping to 20% of the maximum value of the first derivative.

[0080] The present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon. When the computer program is executed by a processor, the method for detecting coagulation indicators based on ultrasonic guided waves as described above is implemented.

[0081] Example 3

[0082] In a specific embodiment, a viscoelastic hemostasis detection method based on ultrasonic guided waves is applied to coagulation assessment in adult patients undergoing surgical procedures, comprising:

[0083] 1. Study population

[0084] This example was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (2022-0951), and the trial protocol has been registered with ClinicalTrials.gov (NCT05921799). Preoperative consent was obtained from the subjects and their families, and signed informed consent was obtained.

[0085] The study enrolled patients at high risk for bleeding or thrombosis who underwent surgery at the Second Affiliated Hospital, Zhejiang University School of Medicine between September 2024 and February 2025. Inclusion criteria included patients undergoing surgery at the Second Affiliated Hospital, Zhejiang University School of Medicine; age ≥ 18 years; a preoperative Caprini score ≥ 5, a preoperative medical or surgical bleeding score indicating bleeding risk, or a clinically determined risk of thrombosis or bleeding. Preoperative use of anticoagulants or antiplatelet drugs was not an exclusion factor.

[0086] 2. Sample size estimation

[0087] According to preliminary experiments, the method of the present invention has a sensitivity of 90% and a specificity of 90% for decreased coagulation factors (TEG-R>10min). α=0.05 and β=0.2 are selected. According to the results of our team's previous preliminary experiments, the incidence of abnormal TEG-R prolongation is about 13%. A total of 70 subjects are required for PASS calculation, and there are 9 cases in the positive group.

[0088] 3. Caprini Scoring Criteria

[0089] The following are the risk factors and their corresponding scores, depending on the patient's specific situation:

[0090] (1) 1 sub-item: age 40-59 years; planned minor surgery; obesity (BMI>30 kg / m 2) ; lower extremity edema; varicose veins; pregnancy or postpartum (1 month); oral contraceptives or hormone replacement therapy; acute myocardial infarction (1 month); congestive heart failure (1 month); severe pulmonary disease, including pneumonia (1 month); sepsis (1 month); bedridden medical patient; history of inflammatory bowel disease; history of major surgery (1 month); abnormal pulmonary function (e.g., chronic obstructive pulmonary disease); history of unexplained fetal demise, recurrent spontaneous abortion (>3 times), preterm labor due to toxemia or growth restriction.(2) 2 points: age 60-74 years; major surgery (<60 minutes); laparoscopic surgery (>60 minutes); arthroscopic surgery (>60 minutes); recent major surgery; cast immobilization (1 month); central venous catheter; bed rest for more than 72 hours; malignancy (past or present).(3) 3 points: age >75 years; history of deep vein thrombosis or pulmonary embolism; family history of thrombosis; positive for Factor V Leiden; positive for prothrombin 2010A; positive for anticardiolipin antibodies; positive for lupus anticoagulant; elevated serum homocysteine; heparin-induced thrombocytopenia; not listed congenital or acquired predisposition to thrombosis.(4) 5 points: stroke (1 month); acute spinal cord injury (paralysis) (1 month); multiple trauma (1 month); hip, pelvic, or lower extremity fracture; elective lower extremity joint replacement.

[0091] 4. Medical bleeding score

[0092] Any of the following is considered to be at high risk of bleeding, including active peptic ulcer, bleeding event within 3 months prior to admission, and platelet count less than 50 x 10 9 / L; and three or more of the following: age >85 years, liver dysfunction (INR >1.5), severe renal dysfunction (glomerular filtration rate <30 ml / min-m 2 2), ICU admission, central venous catheter, rheumatic disease, presence of malignancy, and male.

[0093] 5. Surgical bleeding score

[0094] The surgical inpatient bleeding risk assessment table mainly assesses the risk of bleeding in patients from two aspects of basic diseases and surgery-related factors. In the basic disease-related factors, active bleeding, bleeding event within 3 months, severe liver and kidney dysfunction, platelet count less than 50 x 10 9High-risk factors include: low blood pressure (>100 mL / L), uncontrolled hypertension, lumbar puncture or epidural or spinal anesthesia, use of anticoagulants, antiplatelet drugs, or thrombolytic drugs from 4 hours before surgery to 12 hours after surgery, coagulopathy, active peptic ulcer, and known or untreated bleeding disorders. Among surgery-related factors, abdominal surgery (preoperative anemia, complex surgery such as combined surgery or surgery with high separation difficulty), duodenectomy, sepsis, pyorrhea, surgical site bleeding, liver resection (primary liver cancer or low preoperative hemoglobin and platelet counts), cardiac surgery (prolonged extracorporeal circulation), thoracic surgery (pneumonectomy or extended resection), craniotomy, spinal surgery, spinal trauma, and free flap reconstruction surgery all significantly increase the patient's bleeding risk.

[0095] 6. Data Collection

[0096] Gender, age, body mass index (BMI), preoperative medication history (antiplatelet drugs, anticoagulants) and type of surgery.

[0097] 7. Research Plan

[0098] Before or after anesthesia induction, collect a 2.7 mL whole blood sample by arterial puncture or using an existing arterial catheter. The sample is placed in an anticoagulant tube containing 3.2% citrate for TEG and the method described in the present invention. Ensure that all tests are completed within 2 hours.

[0099] (1) TEG test: 1 mL of blood is drawn from the collected whole blood sample and placed in a sample cup pre-filled with kaolin to activate the endogenous coagulation system. Before the test begins, 20 μL of calcium chloride solution is added to the sample cup to recalcify it. Subsequently, 340 μL of the kaolin-whole blood mixture is drawn and placed in the TEG device for testing. This process dynamically monitors the entire coagulation process of blood from liquid to gel state, generating a series of parameters reflecting the blood coagulation function, including R time, K time, α angle, MA value, and LY30.

[0100] (2) Detection by the method of the present invention: 68 μL of the kaolin-whole blood mixture is drawn from the above-mentioned kaolin cup and placed in a sample tube, followed by the addition of 4 μL of calcium chloride solution for recalcification, and then the detection is started. The coagulation viscoelasticity analysis is achieved by utilizing ultrasonic guided wave technology to generate a series of parameters reflecting the coagulation function of the blood, including CIT, CST, θ angle, MCF value and LT. The detection method of the present invention is for research purposes only, and the results generated are not visible to the perioperative team. Clinical decisions are entirely based on standard nursing procedures.

[0101] 8. Statistical Analysis

[0102] The data of this example were analyzed using SPSS 26 statistical software (IBM, Armonk, NY, USA), MATLAB, and GraphPad Prism 9.1.0 software. Differences were considered statistically significant when P < 0.05. Normality tests were performed using the Shapiro-Wilk test. Non-normally distributed continuous variables were expressed as median (interquartile range), and normally distributed continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as frequency (percentage).

[0103] 9. Correlation analysis

[0104] To evaluate the correlation between the parameters of the method described in the present application and the corresponding indicators of the TEG 5000 system, a linear regression model was used for statistical analysis. The strength of the correlation between the two sets of data was quantified by calculating the Pearson correlation coefficient (r value), and was interpreted according to the following criteria:

[0105] 0.00-0.19: very weak correlation, almost no correlation.

[0106] 0.20-0.39: weak correlation, there is a slight linear trend, but the correlation is weak.

[0107] 0.40-0.59: moderate correlation, the correlation is relatively significant, but not completely consistent.

[0108] 0.60-0.79: strong correlation, the parameters of the method described in the present application and the TEG indicators have a high degree of consistency.

[0109] 0.80-1.0: very strong correlation, indicating that the two have a very close linear relationship.

[0110] 10. Receiver Operating Characteristic Curve (ROC) analysis

[0111] To evaluate the discriminant ability of the parameters of the method described in the present application for TEG values, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to quantify the discriminant ability of the parameters of the method described in the present application, where the AUC value ranges from 0.5 (no discriminant ability) to 1.0 (perfect discriminant ability). Sensitivity and specificity were used to evaluate diagnostic ability, with better diagnostic performance closer to 100%.

[0112] Determination of the optimal cutoff value: the Youden J index (sensitivity + specificity - 1) was used to find the corresponding optimal cutoff value on the ROC curve, ensuring the maximum discriminant performance of the model.

[0113] Curve drawing: ROC curve is generated to intuitively present the performance of the method parameters in discriminating TEG abnormal values through the relationship between the vertical axis of sensitivity (true positive rate) and the horizontal axis of 1-specificity (false positive rate).

[0114] 11. Consistency analysis

[0115] To further verify the consistency of the method of the present application with the results of TEG, according to the linear regression model fitting function, each parameter of the method of the present application is corrected to convert it into a predicted parameter. Subsequently, the consistency of the method of the present application with the results of TEG is comprehensively analyzed by using Bland-Altman (BA) chart. The 95% confidence interval of the average difference between the two methods is used to test the null hypothesis that the difference is not significantly different from 0. The consistency limit is defined as the lower limit of the 95% confidence interval of the average difference minus 1.96 SD and the upper limit of the 95% confidence interval of the average difference plus 1.96 SD, and about 95% of the observations should be included within the consistency limit. Although the manufacturer has not defined the clinically acceptable TEG consistency limit so far, previous studies have defined this limit as about ±10% a priori.

[0116] 12. Research results

[0117] 12.1 Basic characteristics of the population

[0118] A total of 71 surgical patients were included in this example, and the average body mass index (BMI) of the subjects was 23.5±3.7. Regarding the distribution of gender, males accounted for 47.9% (34) and females accounted for 52.1% (37). In terms of surgical type, 45.1% of the subjects underwent orthopedic surgery, 16.9% underwent cardiac and vascular surgery, and 5.6% underwent liver surgery. In terms of preoperative anticoagulant use, 7% of the subjects took antiplatelet drugs, 39.4% used heparin, 1.4% took vitamin k antagonists, and 7% of the patients had combined anticoagulant use. The demographic statistics of the patients are summarized in Table 1.

[0119] A total of 71 samples were obtained in this example, each of which was successfully tested using the method of the present application and was able to be compared with TEG. In the entire study, the first indicator of the method of the present application was obtained 179.7±51 seconds (3.0±1.0 minutes) after the start of the test, and the final results of the coagulation-related parameters were obtained within 625.3±308.9 seconds (10.4±5.1 minutes) after the start of the test.

[0120] Table 1

[0121] Feature N=71 # ]]> Weight 61.2±8.8 BMI 23.0±2.9 Gender Male 34(47.9％) Female 37(52.1％) Operation Orthopedic surgery 32(45.1％) Cardiac and vascular surgery 12(16.9％) Liver surgery 4(5.6％) Other 23(32.4％) Preoperative anticoagulant Antiplatelet drug 5(7.0％) Heparin 28(39.4％) Vitamin K antagonist 1(1.4％) Multiple anticoagulants 5(7.0％)

[0122] #Continuous variables are expressed as mean ± standard deviation or median (interquartile range) or number of patients n (%); BMI, body mass index.

[0123] 12.2 Correlation Analysis between the Method of the Present Invention and the Corresponding TEG Parameters

[0124] The whole blood sample of the same patient was tested by TEG and the method of the present invention at the same time. Figure 5 As shown in (A)-(B), the R time in the TEG test results and the clot initiation time (CIT) of the test results of the method of the present invention, and the K time in the TEG test results and the clot formation time (CST) of the test results of the method of the present invention are significantly linearly correlated, and the Pearson correlation coefficients are 0.98 and 0.96 (P<0.001), respectively, indicating a high degree of consistency between the two in characterizing the key stages of the coagulation process. The high correlation between the R time in the TEG test results and the CIT of the test results of the method of the present invention is because both obtain results by activating the intrinsic coagulation pathway. Taking into account that the blood sampling site (artery or vein) is significantly affected by the blood sampling strength and coagulation time, the blood sampling route is controlled in this embodiment, that is, from arterial catheterization or arterial puncture. The CIT and CST indicators obtained by the method of the present invention are less than the R and K times of the TEG test results. This is because the blood volume of the blood sample cup used in the TEG test is larger and the dilution degree is lower, which will shorten the R and K times.

[0125] like Figure 5 As shown in (C)-(D), the scatter plots of the α angle in the TEG test results and the θ angle in the test results of the method of the present invention, and the maximum amplitude (MA) in the TEG test results and the maximum blood clot strength (MCF) in the test results of the method of the present invention show a nonlinear relationship. This is because the TEG test indirectly measures the clot strength by applying mechanical stress, while the detection method of the present invention uses ultrasonic guided waves, which is reflected as a change in the dissipation modulus. Further Spearman correlation analysis showed that the α angle and the θ angle, MA and MCF have a strong correlation, with correlation coefficients of 0.96 and 0.71, respectively (P < 0.001).

[0126] like Figure 6The theta angle of the detection result of the method of the present application and the MCF index were logarithmically converted, and the results showed that the theta angle and the MCF value of the detection result of the present application after conversion were strongly linearly correlated with the corresponding indexes of the TEG detection result, the Pearson correlation coefficients were 0.89 (alpha angle and log2(theta angle)) and 0.82 (MA and log2(MCF)), respectively, and the P values were less than 0.001, indicating that the method of the present application was highly consistent with TEG detection in evaluating coagulation function indexes. Table 2 shows the linear regression analysis results of each index, and the estimated values of the regression slope and intercept and their 95% confidence intervals, the best fitting equation expression, and the Pearson correlation coefficient.

[0127] Table 2 provides the linear regression analysis results, including the estimated values of the regression slope and intercept and their 95% confidence intervals, and the best fitting equation and the Pearson correlation coefficient.

[0128] Table 2

[0129]

[0130]

[0131] CI, confidence interval; CIT, clot initiation time; R, reaction time; CST, clot formation time; K, clotting time; MCF, maximum clot firmness; MA, maximum amplitude; TEG, thromboelastography; the method of the present application, ultrasonic guided wave-based viscoelastic hemostasis test.

[0132] a Pearson correlation coefficient.

[0133] 12.3 ROC analysis

[0134] In this embodiment, ROC analysis was performed to evaluate the ability of the parameters of the method of the present application to distinguish specific values of the corresponding TEG detection, and the results of the ROC analysis are shown in Table 3. The parameters of the method of the present application have very strong diagnostic consistency with the TEG parameters at different cutoff values, and can effectively distinguish between high and low coagulation states.

[0135] Table 3

[0136]

[0137]

[0138] 12.4 Consistency analysis

[0139] Based on the best fitting equation, the clot initiation time (CIT), clot formation time (CST), theta angle (theta Angle) and maximum clot strength (MCF) indicators obtained by the method of the application are converted to obtain correction coefficients (CIT_pred, CST_pred, theta_pred and MCF_pred), and the bias and consistency range of the method of the application and the TEG detection results are evaluated by Bland-Altman graph.

[0140] As shown in Figure 7 As shown in (A) of the present application, the mean (± standard deviation) of the difference between CIT_pred and R time in the TEG detection result is 0±0.48 min, and the 95% consistency limit is in the interval of-0.90-0.97 min, and 8.4% (6 / 71) of the data points are outside the limit.

[0141] As shown in Figure 7 As shown in (B) of the present application, the mean of the difference between CST_pred and K time in the TEG detection result is 0±0.32 min, and the 95% consistency limit is-0.60-0.60 min, and 4.2% (3 / 71) of the data points are outside the limit.

[0142] As shown in Figure 7 As shown in (C) of the present application, the mean of the difference between theta_pred and alpha angle in the TEG detection result is-0.3±6.15°, and the 95% consistency limit is-12.4-11.7°, and 7.0% (5 / 71) of the data points are outside the limit.

[0143] As shown in (D) of the present application, the mean of the difference between MCF_pred and MA value in the TEG detection result is 0.8±5.43 mm, and the 95% consistency limit is-9.8-11.7 mm, and only 2.8% (2 / 71) of the data points are outside the limit.

[0144] The above results show that the detection indicators of the method of the application and the TEG detection result indicators have very high consistency.

[0145] In the treatment of intraoperative bleeding, time is the most valuable and non-wastable resource. The development of an instant coagulation function detection technology that can quickly output detection results and guide the precise use of blood products is crucial for the realization of perioperative coagulation management. Compared with TEG, which takes about 30 minutes to complete the final result (such as MA) detection, the method of the application only takes 10.4±5.1 minutes (mean), significantly shortening the detection time of coagulation indicators and improving the detection efficiency, providing time guarantee for intraoperative emergency coagulation function evaluation and rational application of blood products, and being conducive to improving the clinical prognosis of patients.

[0146] Those skilled in the art can clearly understand the implementation of the various embodiments by means of software and necessary general hardware platforms through the description of the above embodiments, and of course, the implementation can also be through hardware. Based on such understanding, the above technical solutions can be embodied in the form of a software product, and the computer software product can be stored in a computer readable storage medium, such as a ROM / RAM, a magnetic disk, an optical disk, etc., and includes a plurality of instructions to make a computer device (which can be a personal computer, a server, or a network device, etc.) execute the method described in each embodiment or some parts of the embodiment.

[0147] The principles and implementation of the present application are described herein by applying specific examples, and the above description of the embodiments is only for the purpose of helping to understand the method of the present application and its core idea; at the same time, for those skilled in the art, according to the idea of the present application, there will be changes in the specific implementation and application range. In view of the above, the content of the specification should not be understood as a limitation of the present application.

Claims

1. A coagulation index detection system based on ultrasonic guided waves, characterized in that: include: An ultrasonic guided wave excitation and detection module includes a permanent magnet, a coil, and a magnetostrictive capillary tube. The magnetostrictive capillary tube is filled with a blood sample to which a coagulation reagent has been added, the coil is wound around the magnetostrictive capillary tube, and the permanent magnet is used to provide a static magnetic field. The ultrasonic guided wave excitation and detection module excites and detects the ultrasonic guided wave through the magnetostrictive effect and the inverse magnetostrictive effect to obtain the ultrasonic guided wave attenuation. An acquisition and storage module is connected to the ultrasonic guided wave excitation and detection module, and is used to acquire data output by the ultrasonic guided wave excitation and detection module, store the data, and upload it to the main controller; Temperature control module, used to maintain a constant temperature of the testing environment; The main controller, as the core of the system, is used to calculate the viscoelastic changes of blood samples through ultrasonic guided wave attenuation, obtain coagulation indicators through real-time signal processing and data analysis, and display the test results.

2. The blood coagulation index detection system based on ultrasonic guided waves according to claim 1, characterized in that: The working principle of the ultrasonic guided wave excitation and detection module is: Ultrasonic guided waves are excited by the magnetostrictive effect: Under a static magnetic field, the magnetostrictive capillary tube is affected by the dynamic magnetic field of the coil to generate ultrasonic guided waves. As the ultrasonic guided waves propagate, they are detected by the coil as an induced voltage through the inverse magnetostrictive effect. When the magnetostrictive capillary tube is filled with blood, the amplitude of the ultrasonic guided waves attenuates as the blood viscosity changes, and the ultrasonic guided wave attenuation is obtained.

3. The blood coagulation index detection system based on ultrasonic guided waves according to claim 1, characterized in that: The working principle of the main controller is: The complex wave number is derived based on the hysteresis model of viscoelastic materials, the attenuation of ultrasonic guided waves, and the true wavelength; thereby, the complex wave velocity V is calculated, and the loss modulus E is calculated, thereby obtaining the coagulation characteristic curve, realizing the quantitative characterization of the viscosity change of blood samples during the coagulation and fibrinolysis processes.

4. A method for detecting coagulation indexes based on ultrasonic guided waves, applied to a coagulation index detection system based on ultrasonic guided waves according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1. Collect blood samples and prepare the blood samples to be tested; S2, injecting the prepared blood sample into the magnetostrictive capillary and applying an ultrasonic guided wave excitation signal; S3. Real-time monitoring of the attenuation changes of the ultrasonic guided waves of the magnetostrictive capillary, calculation of the viscoelastic changes of the blood sample, and drawing of the viscoelastic change curve; S4. After obtaining the viscoelasticity change curve, the corresponding coagulation index of the sample is calculated; S5. Output the test results for evaluating coagulation function and fibrinolysis status.

5. The method for detecting blood coagulation indexes based on ultrasonic guided waves according to claim 4, characterized in that: In S4, the calculated coagulation indexes of the sample are used to compare the various indexes of the TEG test results of the gold standard method, including: The clot initiation time (CIT) is defined as the time interval from the placement of a blood sample into the coagulation index detection system to the onset of initial fibrin formation. This indicator reflects the enzymatic reaction stage of the coagulation process and is comparable to the R time of the gold standard TEG test result. CIT is determined by the first-order derivative of the coagulation characteristic curve. The clot stability time (CST) is defined as the time it takes for a blood sample to form a clot, reflecting the kinetics of clot formation during coagulation and is comparable to the K time of the gold standard TEG test results. CST is determined by the coagulation profile curve. Angle θ is used to measure the rate of fibrin formation and cross-linking, reflecting the fibrinogen content in the blood sample and comparing it to the α angle of the gold standard TEG test result. θ is defined as the maximum angle formed during the rising phase of the coagulation characteristic curve. The maximum clot strength (MCF) is used to characterize the peak dynamic characteristics of fibrin binding to platelets mediated by platelet glycoprotein GPIIb / IIIa. This indicator represents the maximum strength that a fibrin clot can achieve and is compared with the MA value of the gold standard TEG test result. MA is defined as the dissipation modulus value corresponding to the first-order derivative of the coagulation characteristic curve when it drops to 20% of the maximum value of the first-order derivative.

6. A non-transitory computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the method for detecting coagulation indicators based on ultrasonic guided waves as claimed in claim 4 is implemented.

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