Methodologies and reagents for detecting fibrinolysis and hyperfibrinolysis in a blood sample using viscoelastic analysis

Patent metadata

Field	Value
Publication number	US-9354243-B2
Application number	US-201414270269-A
Country	US
Kind code	B2
Filing date	May 5, 2014
Priority date	May 5, 2014
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

In some embodiments, the invention provides methods for detecting fibrinolysis or hyperfibrinolysis in a blood sample from a patient. The method includes subjecting a first portion of a blood sample comprising reduced platelet function to viscoelastic analysis in the absence of an inhibitor of fibrinolysis to obtain a coagulation characteristic of the first portion at a time point; and subjecting a second portion of the blood sample comprising reduced platelet function to viscoelastic analysis in the presence of an inhibitor of fibrinolysis to obtain a coagulation characteristic of the second portion at the time point; wherein a difference between the coagulation characteristic of the first portion and the coagulation characteristic of the second portion indicates fibrinolysis or hyperfibrinolysis in the blood sample.

First claim

What is claimed is:

1. A method for detecting fibrinolysis or hyperfibrinolysis in a blood sample, comprising:
a) subjecting a first portion of a blood sample comprising reduced platelet function, to viscoelastic analysis in the absence of an inhibitor of fibrinolysis to obtain a coagulation characteristic of the first portion at a selected time point;
b) subjecting a second portion of the blood sample comprising reduced platelet function to viscoelastic analysis in the presence of an inhibitor of fibrinolysis to obtain a coagulation characteristic of the second portion at the selected time point; and
c) comparing the coagulation characteristic of the first portion to the coagulation characteristic of the second portion to detect a difference;
wherein a difference between the coagulation characteristic of the first portion and the coagulation characteristic of the second portion indicates fibrinolysis or hyperfibrinolysis in the blood sample.

2. The method of claim 1 , wherein the coagulation characteristic is an amplitude of an output of the viscoelastic analysis.

3. The method of claim 1 , wherein the coagulation characteristic is a first derivative of an amplitude of an output of the viscoelastic analysis.

4. The method of claim 1 , wherein the time point is at a time of maximum clot strength of the first portion.

5. The method of claim 1 , wherein the time point is between about 15 to about 35 minutes after the viscoelastic analysis is started.

6. The method of claim 1 , wherein the time point is less than 20 minutes after the viscoelastic analysis is started.

7. The method of claim 1 , wherein the time point is obtained is at a time that clot firmness reaches 20 mm in the first portion of the blood sample.

8. The method of claim 1 , wherein the difference between the coagulation characteristic of the first portion and the coagulation characteristic of the second portion that is at least 1% indicates fibrinolysis or hyperfibrinolysis in the blood sample.

9. The method of claim 1 , wherein the difference between the coagulation characteristic of the first portion and the coagulation characteristic of the second portion that is at least 2% indicates fibrinolysis or hyperfibrinolysis in the blood sample.

10. The method of claim 1 , wherein the blood sample comprising reduced platelet function comprises an inhibitor of platelet function.

11. The method of claim 10 , wherein the inhibitor of platelet function is a glycoprotein IIb/IIIa receptor inhibitor.

12. The method of claim 11 , wherein the glycoprotein IIb/IIIa receptor inhibitor is selected from the group consisting of abciximab, eptifibatide, and tirofiban.

13. The method of claim 10 , wherein the inhibitor of platelet function is an adenosine diphosphate (ADP) receptor inhibitor, adenosine reuptake inhibitor, or a thromboxane inhibitor.

14. The method of claim 10 , wherein the inhibitor of platelet function is cytochalasin D.

15. The method of claim 1 , wherein the blood sample comprising reduced platelet function is a platelet-reduced blood sample.

16. The method of claim 15 , wherein the platelet-reduced blood sample is obtained by physical removal of the platelets from the blood sample.

17. The method of claim 1 , wherein the inhibitor of fibrinolysis is tranexamic acid.

18. The method of claim 1 , wherein the inhibitor of fibrinolysis is selected from the group consisting of consisting of aminocaproic acid (ε-aminocaproic acid) and aprotinin.

19. The method of claim 1 , wherein the viscoelastic analysis is performed using a hemostasis analyzer.

20. The method of claim 1 , wherein the viscoelastic analysis is performed using a container containing the sample on an interior of the container and a pin, wherein the pin moves relative to the container.

21. The method of claim 1 , wherein the viscoelastic analysis is performed using a container containing the sample on an interior of the container and a pin, wherein the container moves relative to the pin.

22. The method of claim 1 , wherein the inhibitor of fibrinolysis is included in a coating on an interior of a container containing the sample.

23. The method of claim 1 , wherein the inhibitor of fibrinolysis is added to the sample.

24. The method of claim 10 , wherein the inhibitor of platelet function is included in a coating on an interior of a container containing the sample.

25. The method of claim 10 , wherein the inhibitor of platelet function is added to the sample.

26. The method of claim 1 , wherein the blood sample is obtained from a patient.

27. The method of claim 26 , wherein if fibrinolysis or hyperfibrinolysis is detected, the patient is responsive to the inhibitor of fibrinolysis.

28. A method for identifying an inhibitor of fibrinolysis that will achieve a beneficial response in a patient undergoing or likely to undergo fibrinolysis or hyperfibrinolysis, comprising:
a) subjecting a first portion of a blood sample comprising reduced platelet function from the patient to viscoelastic analysis in the absence of an inhibitor of fibrinolysis to obtain a coagulation characteristic of the first portion at a selected time point;
b) subjecting a second portion of the blood sample comprising reduced platelet function from the patient to viscoelastic analysis in the presence of a first inhibitor of fibrinolysis to obtain a coagulation characteristic of the second portion at the selected time point;
c) subjecting a third portion of a blood sample comprising reduced platelet function from the patient to viscoelastic analysis in the presence of a second inhibitor of fibrinolysis to obtain a coagulation characteristic of the third portion at the selected time point; and
d) comparing a first difference between the coagulation characteristic of the first portion and the coagulation characteristic of the second portion in the presence of the first inhibitor, and a second difference between the coagulation characteristic of the first portion and the coagulation characteristic of the third portion in the presence of the second inhibitor,
wherein the patient will have a beneficial result from treatment with the first inhibitor if the first difference is greater than the second difference, and the patient will have a beneficial result from treatment with the second inhibitor if the second difference is greater than the first difference.

29. The method of claim 28 , wherein the patient is human.

30. The method of claim 28 , wherein the first inhibitor of fibrinolysis is tranexamic acid.

31. The method of claim 28 , wherein each of the first inhibitor of fibrinolysis and the second inhibitor of fibrinolysis is selected from the group consisting of ε-aminocaproic acid, tranexamic acid, and aprotinin, wherein the first inhibitor of fibrinolysis and the second inhibitor of fibrinolysis are not the same.

32. The method of claim 1 , wherein the inhibitor of fibrinolysis is a combination of two or more inhibitors selected from the group consisting of aminocaproic acid (ε-aminocaproic acid), tranexamic acid, and aprotinin.

33. The method of claim 10 , wherein the inhibitor of platelet function is a combination of two or more different inhibitors selected from the group consisting of abciximab, eptifibatide, tirofiban, an adenosine diphosphate (ADP) receptor inh

Assignees

• Haemonetics Corp
• Univ Colorado Regents

Inventors

• Chapman Michael P
• Moore Ernest E
• Norem Katherine M

Classifications

• G01N33/86 Primary

  involving blood coagulating time {or factors, or their receptors} · CPC title

• C12Q1/56

  involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen · CPC title

• G01N33/49

  Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)} · CPC title