Prednance bag system containing an anticoagulant and blood bag system.

Description

[0001] The invention relates to a blood bag system comprising a pre-donation bag system with a pre-donation bag for filling with whole blood during blood collection, wherein an anticoagulant is added to the whole blood in the pre-donation bag, so that the filling of the whole blood from the pre-donation bag into sample containers for blood analysis can only take place in the laboratory and not at the site of blood donation. Furthermore, a corresponding method for blood collection using the blood bag system and for the analysis of the whole blood of each donor is proposed. INTRODUCTION AND STATE OF THE ART

[0002] Blood products are stored by hospitals, blood banks, and other medical facilities for use in blood transfusions. From a single whole blood donation, various blood products are obtained to administer the specific blood components a patient needs. This separation significantly reduces the risk of side effects and incompatibilities. Furthermore, by separating the blood into its components, optimal conditions can be achieved for each component in terms of shelf life, storage capacity, and efficacy.

[0003] During blood donation, whole blood is first collected from individual donors. The blood of each donor, known as whole blood, is collected in a closed blood bag system. This system is designed so that the whole blood is initially collected in a whole blood bag (often also called a collection bag) and then undergoes processing and separation treatments. The resulting individual blood components are then transferred to separate, connected bags (transfer bags). In this process, the blood from a donor is separated into its components. This separation is achieved through centrifugation. Centrifugation produces an upper layer of plasma, possibly a thinner intermediate layer known as the "buffy coat layer" containing leukocytes and platelets, and a lower layer of erythrocytes.

[0004] It is necessary to separate the leukocytes. This is done by filtration before or after the separation step by centrifugation. Furthermore, the whole blood or the individual blood products can undergo a virus inactivation step. In many applications (as also for the present invention), a blood bag system is designed such that a blood bag system can be assigned to only one donor.

[0005] The above procedure requires careful labeling of the sample containers so that they can be clearly assigned to a donor and the associated blood bag system.

[0006] A large number of different blood bag systems are known for collecting, separating, and storing blood components. Typically, a closed, sterile blood bag system, such as the Fenwal type, is used to collect whole blood and separate it into its components. This system contains a relatively large whole blood bag for collecting a blood donation, a filter, and one or more transfer bags connected to the whole blood bag by connecting tubes.

[0007] The various blood collection systems generally share the common feature that whole blood flows directly from the donor into the whole blood bag without the use of external pumps or similar devices. Blood collection involves inserting a venous access device, such as a venipuncture needle, into the donor's vein and drawing blood from the donor using this device. The needle is connected via an adapter to a tube through which the whole blood flows into the blood bag. The venous access device (such as a venipuncture needle), the tubing, and the bag constitute the blood collection system, which is pre-sterilized and disposed of after single use.

[0008] The whole blood bag contains an anticoagulant because blood begins to clot after a certain time and adheres to the walls of the plastic surfaces it comes into contact with, or otherwise coagulates. The anticoagulants used must be listed in the European Pharmacopoeia. They are typically CPD (citrate-phosphate dextrose) or ACD (acid-citrate dextrose).

[0009] An important consideration for any blood collection technique or blood bag system is ensuring that the blood bag system is not contaminated by airborne bacteria or other foreign substances that could compromise the system's sterility. Thus, the sterility of the blood bag system described above is ensured, according to current best practices, by minimizing or preventing exposure of the flow paths and the interior of the bags to the external environment. Such systems are generally referred to as "closed systems."

[0010] With every blood donation, a donor's whole blood is tested for blood type and the presence of pathogens such as viruses and bacteria. Typically, testing the collected blood requires taking one or more samples from each donor at or near the time of collection. However, taking samples from the whole blood bag while exposing the collected blood to the external environment is undesirable. Furthermore, the anticoagulant in the whole blood bag often interferes with the analysis.

[0011] During whole blood donation, the blood collection process typically involves the simultaneous filling of sample containers on-site. These containers are necessary for laboratory analysis. An anticoagulant is present in the sample containers to prevent the proteins in the blood from precipitating before laboratory testing. This anticoagulant can be, for example, sodium citrate, CPD (citrate-phosphate-dextrose), CP2D (citrate-phosphate-double-dextrose), CPDA (citrate-phosphate-dextrose-adenine), or ACD (acid-citrate-dextrose). Sample containers are recommended, for example, in WO 2003 / 095974 A2.

[0012] In one example, blood is collected for sampling in an enlarged section of the tubing leading to the whole blood bag. Once the desired blood volume for sampling has been collected in the enlarged section, the tubing between the whole blood bag and the enlarged section is closed, the donor's needle is removed, and the blood from the tubing section is transferred to sample containers. Such a blood bag system has proven less suitable for the present application.

[0013] A blood bag system for umbilical cord blood collection has been proposed, for example, in DE 202013011482 U1. Here, the whole blood bag serves as a freezing bag, and the enlarged section of tubing acts as a reservoir. Other blood bag systems are known from CN 201631679 U or DE 3030020 A1, but without a pre-donation bag. CA2484628 A1 and US2006 / 212020 A1 relate to sampling vessels for whole blood, among other things, using EDTA as an anticoagulant. TASK OF INVENTION

[0014] Although known techniques generally function satisfactorily, efforts continue to be made to improve blood collection and the recovery of blood products, particularly with regard to blood bag systems that allow for a higher degree of automation. The object of the present invention is to simplify and automate whole blood analysis and to simplify and systematize sampling. SUMMARY OF THE INVENTION

[0015] These and other problems are solved by the subject matter of the independent patent claims. Preferred embodiments are the subject matter of the dependent claims or described below.

[0016] The present invention relates to a blood bag system comprising a predonation bag system which enables the withdrawal of blood from a predonation bag as part of the blood bag system into sample containers no longer locally at the site of blood collection, but centrally and preferably automatically in a laboratory during or during blood processing.

[0017] The pre-donation bag system includes at least one pre-donation bag, a venipuncture adapter, and a blood collection line with a) a first tube section that can be closed off from the blood collection line as a supply from the blood collection line into the predonation bag and b) a second tube section as a supply from the blood collection line into other parts of the blood bag system, e.g. into a whole blood bag (whereby the whole blood bag is not part of the predonation bag system), in particular directly into a whole blood bag, The pre-donation bag or the first section of tubing, or both, must contain an anticoagulant for whole blood, and the anticoagulant must be EDTA. Specifically, the anticoagulant must be K2-EDTA (dipaspotassium EDTA) and / or K3-EDTA (tripotassium EDTA). The sample container then no longer needs to contain an anticoagulant.

[0018] The first and second tubing sections branch off from the blood collection line. The second tubing section can also be the same line as the blood collection line, which, after the branching off of the first tubing section, is then called the second tubing section, and conversely, the first tubing section can also be the same line as the blood collection line, which, after the branching off of the second tubing section, is then called the first tubing section.

[0019] The advantage of centralized filling of sample containers lies, among other things, in the control of the process steps. Extensive donor information is stored in the blood donation service provider's database and can be accessed, allowing decisions regarding the number and type of necessary tests, and thus the sample containers to be filled, to be made only after comparison with the available data. Another advantage is the centralized, automated sealing of the donation bags. This significantly reduces the risk of the bag becoming airtight compared to sealing or other methods of sealing at the blood donation site.

[0020] For transport and subsequent filling of the sample containers, the whole blood in the pre-donation bag of the blood bag system, from which the sample container(s) will later be filled, is anticoagulated with a suitable anticoagulant. This prevents the blood from clotting. Surprisingly, EDTA, especially K2-EDTA and / or K3-EDTA, has proven to be a suitable anticoagulant for whole blood in the pre-donation bag. K2-EDTA or K3-EDTA can be used in infectious disease and blood group serology laboratories, as well as in PCR analysis and molecular blood group determination. These laboratories perform a large number of tests (e.g., >10), all of which must be converted to the same anticoagulant.

[0021] Another characteristic of the blood bag systems with pre-donation bag system according to the invention is that the anticoagulant in the whole blood of the pre-donation bag is different from that in the whole blood bag. This requires that the whole blood in the pre-donation bag can be collected in such a way that neither the anticoagulant for the pre-donation bag nor the whole blood in which the anticoagulant is dissolved comes into contact with the donor or donor blood or the whole blood in the whole blood bag; in particular, contact or mixing with the whole blood in the whole blood bag must be avoided. For example, CPD, CPDA1, and / or CP2D can then be used as the anticoagulant in the whole blood bag.

[0022] The invention further relates to a method for taking whole blood using the blood bag system, wherein the anticoagulant-treated whole blood or a part thereof is filled from the predonation bag into one or more sample containers after transport of the predonation bag to a laboratory, preferably automatically, and the sample container is subjected to an analysis or the sample containers are each subjected to different analyses.

[0023] The number of sample containers per pre-donation bag can be determined based on the donor and a comparison with their entry in a donor database. For example, the database can indicate which type of analysis is necessary for each donor and how many sample containers are required. Each donor is assigned a pre-donation bag or blood bag system. Automation allows for the selection of the correct number of sample containers, avoids unnecessary containers, and groups sample containers for the same tests or sequences of the same tests for different donors. For example, first-time donors undergo a larger number of tests and therefore require more sample containers. Furthermore, the step of filling and labeling the sample containers at the blood donation site is eliminated. DETAILED DESCRIPTION OF THE INVENTION

[0024] According to the present invention, whole blood is not sampled from the whole blood bag itself, but the flow path of the whole blood is clamped before the whole blood bag and the whole blood taken from the donor is first diverted into the sample bag (predonation bag), e.g. via a T or Y branch, until the flow path to the predonation bag is closed, in particular by a closure in the area of ​​the first tube section that is initially opened and later closed, and the flow path to the whole blood bag is opened, in particular by a closure in the area of ​​the second tube section that is initially closed and later opened, in order to fill the whole blood bag.

[0025] In this embodiment, a disposable tubing set is used as part of the blood collection system. This set is positioned on the main flow path from the blood collection line into the second tubing section, with the first tubing section acting as a dead end. The set includes the donation bag, a first tubing section, and an adapter for the sample container, which serves as the sampling point. Blood can then be drawn from the donation bag, for example, by opening a lid on the adapter, inserting a sample container (e.g., a sample tube) into the adapter, and using a needle in the adapter to pierce the membrane of the sample container. Whole blood then flows through the sampling point into the attached sample container, which may be under negative pressure.

[0026] According to one embodiment of the invention, the internal volume of the pre-donation bag is 10 to 50 mL, particularly 25 to 35 mL, or contains the aforementioned volume of whole blood. In particular, the anticoagulant concentration in the whole blood is 1.2 to 2 mg / mL, preferably 1.4 to 1.8 mg / mL, such as approximately 1.6 mg / mL. The anticoagulant in the pre-donation bag ensures that the desired tests can be performed in the laboratory at staggered intervals using the whole blood in the sample container(s). The anticoagulant used in the pre-donation bag according to the invention does not interfere with the laboratory analysis and thus behaves neutrally in the tests.

[0027] The anticoagulant may be present in the pre-donation bag or in the first section of tubing, preferably beyond the closure in the first section of tubing and towards the pre-donation bag: 1. as a liquid, e.g. dissolved in water, 2. as a coating, i.e. immobilized as part of an interior wall coating, 3. as a solid (e.g. as a tablet), and / or 4. as a solid or liquid in a capsule that opens by external pressure or by dissolution.

[0028] The anticoagulant can, for example, a) be applied as a solid to the inner surface of the first tubing section or a tube inserted into the first tubing section and / or b) be applied as a solid to the inner surface of the predonation bag.

[0029] According to one embodiment of the invention, the anticoagulant is dissolved in water and introduced into the pre-donation bag. This ensures that the EDTA Simply distributed in whole blood when the whole blood flows into the donation bag, for example due to pressure in the donor's bloodstream.

[0030] The anticoagulant can also be immobilized on the inner wall of the pre-donation bag and / or in a section of tubing or a tube inserted into the tubing section leading to the pre-donation bag, downstream of the closure device. This is achieved through contact between the whole blood and the immobilized material. EDTA This dissolves. The coating of the interior walls is done, for example, by spray drying.

[0031] Furthermore, it is possible that a suitable amount of anticoagulant in solid form is contained in the pre-donation bag and that the anticoagulant dissolves in the whole blood as soon as it flows into the pre-donation bag and comes into contact with it, possibly assisted by shaking the pre-donation bag.

[0032] Alternatively, a tablet, for example in a pill compartment, can be placed in the first section of tubing leading to the pre-donation bag and will dissolve as the whole blood flows past it, possibly followed by shaking (manually or on a mixing scale). The tablet can also simply be placed directly into the pre-donation bag.

[0033] In another embodiment, the anticoagulant is contained in a capsule whose shell dissolves upon contact with whole blood or which must be mechanically ruptured to release the anticoagulant into the donation bag or via a supply line to it. For example, the capsule is ruptured when the supply line to the donation bag is sealed downstream of the capsule. Backflow to the donor or towards the whole blood bag must be prevented.

[0034] The first section of tubing has a closure (preferably initially open and later closable). The anticoagulant is preferably located exclusively in the first section of tubing behind the closure and / or in the pre-donation bag (also behind the closure in the first section of tubing).

[0035] A valve or shut-off device, in the form of a lockable mechanical closure that can only be reopened if necessary, in the supply line to the anticoagulation bag ensures that the EDTA or whole blood containing EDTA cannot flow back. This effectively prevents the anticoagulant from coming into contact with the donor and / or the whole blood in the whole blood bag.

[0036] In one embodiment, the closure in the first hose section is initially closed in its home position, can then be opened, and closes on the second closing, in particular irreversibly, meaning it cannot be opened a second time. Alternatively, the closure is initially open in its home position and closes on the first closing, in particular irreversibly, and cannot then be opened a second time.

[0037] The second hose section can, for example, have a snap-off piece with a predetermined breaking point inside the second hose section, which breaks off mechanically, thereby releasing the flow into the whole blood collection bag via the second hose section. Alternatively, but less preferably, the snap-off piece can be located in the first hose section. An example of a possible embodiment of the snap-off piece as an irreversibly opening closure can be found in DE 3030020 A1.

[0038] The central sample container filling process can be implemented in various ways. In one embodiment, the pre-donation bag is separated from the rest of the blood bag system by sterile welding (particularly between the closure of the first tubing section and the pre-donation bag), whereby both ends are sealed by welding, or the supply line can be detached behind the closure when viewed from the pre-donation bag. Welding is achieved, for example, by selectively heating and compressing the tubing section, and separation is achieved, for example, by punching in the weld zone or by creating a tear line as a material weakening in the weld zone. In this way, both tubing ends are sealed by welding.

[0039] Subsequently, the sample containers are filled centrally in the laboratory with blood from the donation bag. This step can be automated. First, the specific preparation number or identification of the donation bag is read, and the required number of sample containers is determined. Each sample container can be uniquely assigned to a specific donation, for example, by marking each container with an identification that allows it to be linked to the donor. This can be done by labeling or by assigning a sample identification and / or a donor identification in a database. The EDTA-treated whole blood is then transferred from the donation bag into the sample container. One way to fill the sample containers is to use an adapter, as described above, which can also be used for manual filling.However, it is also possible to fill the bag directly via a tube or cannula. The cannula can be used to puncture the donation bag and take a sample. Contamination with foreign blood must be avoided.

[0040] If desired, the pre-donation bag system can also be sealed off from the rest of the blood bag system, especially between the clamp on the second tube section and the whole blood bag, by sterile welding (e.g. as described above) to close the second tube section on both sides and to create a separation at the weld point, e.g. by punching, or to pre-emboss a tear line as a material weakening.

[0041] The invention is explained with reference to the following figures, without being limited to them. They show: Fig.1 the pre-donation bag system for the blood bag system and Fig. 2 a blood bag system with a pre-donation bag system.

[0042] Fig. 1 Figure 1 shows a representation of the predonation bag system 1. The predonation bag system 1 comprises a predonation bag 2, a venipuncture needle 3, a blood collection tube 4 from the venipuncture needle 3 to a first Y-connection 5, from which the flow from the blood collection tube 4 continues into a first tube section 6, which ends in the predonation bag 2.

[0043] The other arm of the Y-connection 5 leads into a second tube section 14 which leads to the whole blood bag 21.

[0044] A venipuncture needle 3, used to draw whole blood from the donor, is connected to the free end of the blood collection line 4 via a venipuncture adapter 16. The venipuncture needle 3 is enclosed by a snap-on, conical cap 15. Furthermore, a protective bell 17 is movable along the blood collection line 4 and locks onto the adapter at the end of the blood collection line, so that the protective bell 16 encloses and protects the venipuncture needle 3 and the cap 15.

[0045] The second tubing section 14 branches off from the blood collection line 4 at the other arm of the Y-connection 5. Part of the Y-connection 5 is a break-off piece 18 inserted into this arm, which blocks the flow through the arm of the Y-connection 5. The break-off piece 18 has a hollow sleeve and an olive 19 at its end, which closes the sleeve in the direction of flow. The sleeve seals itself at the other end with a collar within the arm of the Y-connection. By bending the end of the arm, the olive can be broken off along a predetermined breaking point, thus releasing the flow of whole blood into the second tubing section 14 through the sleeve.

[0046] The olive 19 remains at the end of the arm of the Y-piece because its outer circumference has ridges that prevent the olive 19 from being flushed into the second tube section 14, while still allowing blood to pass through the comb-like grooves in the olive. The break-off piece 18 is optional and can likewise be inserted into the first tube section 6 or the arm of the Y-connection 5 that leads into the first tube section 6.

[0047] Furthermore, the second hose section 14 is equipped with a hose clamp 20 that is initially open and later can be closed again, which is closed after the whole blood bag 21 (see Fig. 2 ) is sufficiently filled and should prevent whole blood from flowing back.

[0048] EDTA in tablet form is placed in pill chamber 8 of the first tube section 6. As the blood flows past, the tablet dissolves and releases the EDTA into the whole blood, so that ultimately the whole blood in the pre-donation bag 2 is stabilized by the anticoagulant EDTA.

[0049] A sampling adapter 11 is connected via a second Y-connector 9 to a sampling tube section 10, which is in continuous flow connection with the pre-donation bag 2 via a section of the first tube. When the lid 12 of the sampling adapter 11 is opened, a sample container can be inserted into the cylindrical cavity of the sampling adapter 11 with its septum facing down. Due to the negative pressure within the sample container, the container fills with whole blood containing the anticoagulant. Similarly, additional sample containers, e.g., in the form of sample collection tubes, can be automatically labeled and filled in a laboratory, i.e., not at the blood collection site. These are then collected and administered to the corresponding test in multiples. The arms of the Y-connectors are each part of the corresponding tube sections.

[0050] In Fig. 2 schematically, a blood bag system comprising the pre-donation bag system 1 of the Fig. 1 shown (however, here the sampling adapter 11 is directly connected to the pre-donation bag 2 via the sampling tube section 10 without a second Y-connection).

[0051] During blood collection, the donor's whole blood is drawn into the blood bag system via a venipuncture needle 3. A first tubing section 6, after the Y-connector 5, carries the donor's whole blood to the donation bag 2, and a second tubing section 14 carries it to the whole blood bag 21. The whole blood drawn via the venipuncture needle 3 is initially drawn through the blood collection tubing 4 and the Y-connector 5 into the first tubing section 6, then through an irreversible clamp 7 into the donation bag 2. "Irreversible clamp" 7 means that it is either open in its default state (preferred) or closed in its default state and can be opened, but in both cases cannot be reopened after the initial closure. The donation bag 2 is connected via a sampling tubing section 10 to an adapter 11, which is intended for filling sample containers.Adapter 11 can be opened, revealing a cylindrical guide containing a needle for piercing a septum. Once the predonation bag 2 is sufficiently filled, the irreversible clamp 7 is closed and the reversible clamp 20 in the second tube section 14 is opened, and the olive 19 is also broken off. The whole blood now flows exclusively into the whole blood bag 21, often also called the collection bag. It is also possible that only the initially closed clamp 20 or only the break-off part 18 is located in or on the second tube section.

[0052] During processing into individual preparations, the whole blood in whole blood bag 21 is first centrifuged. Subsequently, the components are separated: erythrocytes into erythrocyte bag 22, plasma into plasma bag 23, and platelets (which remain in whole blood bag 21). In Germany, according to the regulations of the federal authority, the Paul Ehrlich Institute, only leukocyte-depleted blood products or products with a very low leukocyte content may be marketed. Leukocyte depletion means the removal of leukocytes from the preparations. Typically, as exemplified in... Fig. 2The white blood cells are removed from the erythrocyte concentrate using a filter 25, so that the leukocyte content per unit of preparation after filtration is less than 10⁻⁶ leukocytes in bag 24 for the leukocyte-depleted erythrocyte concentrate. Surface-modified polyester fibers can be used as filter media. Filtration occurs through adsorption of the leukocytes. Bag 24 for the leukocyte-depleted erythrocyte concentrate contains an additive solution.

Claims

1. Blood bag system comprising a predonation bag system (1) and at least one whole blood bag (21), wherein the predonation bag system (1) comprises at least: a predonation bag (2), a venipuncture adapter (16) and a blood collection line (4) with a) a first tube section (6) which is sealable with respect to the blood collection line (4) as a feed from the blood collection line (4) into the predonation bag (2) and b) a second tube section (14) as a feed from the blood collection line (4) into the whole blood bag (21), wherein the predonation bag (2) or the sealable first tube section (6) or both comprises / comprise a first anticoagulant for whole blood and the first anticoagulant is EDTA; wherein the predonation bag (2) or the sealable first tube section (6) comprises an adapter (11) for filling of one or more sample containers; and wherein in the whole blood bag (21) a second anticoagulant is contained, which is different from the first anticoagulant and which is not EDTA and is CPD, CPDA1 and / or CP2D.

2. Blood bag system according to claim 1, wherein the first anticoagulant is K2-EDTA or K3-EDTA or both.

3. Blood bag system according to one or more of the preceding claims, wherein the first anticoagulant a) is applied as a solid to the inner surface of the sealable first tube section or of a small tube inserted into the sealable first tube section and / or b) is applied as a solid to the inner surface of the predonation bag (2).

4. Blood bag system according to claim 1 or 2, wherein the first anticoagulant is introduced into the predonation bag (2) dissolved in water.

5. Blood bag system according to one or more of the preceding claims, wherein the predonation bag (2) has a volume of 10 to 50 mL, in particular 25 to 35 mL.

6. Blood bag system according to one or more of the preceding claims, wherein the first anticoagulant is introduced in an amount such that a concentration in the whole blood of the predonation bag (2) of greater than or equal to 1.2 mg / mL, and preferably 1.4 to 1.8 mg / mL is obtained.

7. Blood bag system according to one or more of the claims 1, 2, 5 or 6, wherein the first anticoagulant is introduced as a pill or tablet into the predonation bag (2) or the sealable first tube section, in particular in a pill chamber (8).

8. Blood bag system according to one or more of the preceding claims, wherein the sealable first tube section and the predonation bag (2) are formed as a dead end.

9. Blood bag system according to one or more of the preceding claims, wherein the sealable first tube section has an initially open and later sealable closure (7), in particular later irreversibly closeable.

10. Blood bag system according to one or more of the preceding claims, wherein the first tube section (6) has a break-off part with a predetermined breaking point inside the first tube section (6), which is mechanically broken off and thereby releases the flow into the predonation bag via the sealable first tube section and / or wherein the second tube section (14) has a break-off part (18) with a predetermined breaking point inside the second tube section (14), which is mechanically broken off and thereby releases the flow into the whole blood bag (21) via the first tube section.

11. Blood bag system according to one or more of the preceding claims, wherein the sealable first tube section comprises a sealable closure (7), wherein the first anticoagulant is preferably arranged exclusively in the sealable first tube section behind the closure and / or exclusively in the predonation bag (2).

12. Blood bag system according to one or more of the preceding claims, wherein a reversible clamp is located in the second tube section (14) for opening and closing again and, optionally, reopening the inflow into the whole blood bag (21).

13. Blood bag system according to one or more of claims 1 to 11, wherein a clamp is located in the second tube section (14), which is initially closed, can be opened and then closes again reversibly or irreversibly.

14. Method for central filling of one or more sample containers by means of a blood bag system according to one or more of claims 1 to 13, wherein the whole blood provided with the first anticoagulant or a part thereof from the predonation bag (2) after transportation to a laboratory is filled by means of the adapter (11) into one or more sample containers, preferably automatically, and the sample container is supplied to an analysis or the sample containers are each supplied to different analyses.

15. Method according to claim 14, wherein the number of sample containers per predonation bag (2) is determined as a function of the donor and a comparison with an entry in a database for the donor and the sample containers and their number are labeled with regard to the tests selected by means of the entry in the database and preferably sample containers of different donors, wherein only one defined blood bag system is assigned to each donor, are automatically sorted on the basis of the labeling and are compiled with regard to identical tests or sequences of identical tests for the different donors.