Methods for quality control of prothrombin time (PT) and activated partial thromboplastin time (APTT) assays using coagulation controls

• US 20010004641A1
• Filed: 01/26/2001
• Published: 06/21/2001
• Est. Priority Date: 07/01/1998
• Status: Active Grant

• Current Assignee: Tcoag Ireland Limited
• Original Assignee: Trinity Biotech Manufacturing Limited (MiCo IVD Holdings, LLC)
• Inventors: Hawkins, Pamela L.
• Granted Patent: US 6,528,273 B2
• Time in Patent Office: Days
• US Class Current: 514/560
• CPC Class Codes: G01N 2400/40 Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides
• CPC Class Codes: G01N 2496/05 containing blood cells or plasma
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors
• CPC Class Codes: G01N 33/96 involving blood or serum control standard

Abstract

Coagulation control compositions suitable for use in connection with PT and/or APTT assays are disclosed along with their methods of preparation and methods of use. Preferred coagulation controls comprise plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa. The anticoagulant is preferably a glycosaminoglycan such as heparin, a heparin derivative or a heparin analog. The anticoagulant is preferably combined with (1) an abnormal plasma (e.g. activated plasma or factor-deficient plasma) and/or (2) a primate plasma (e.g. human plasma), and a non-primate mammalian plasma (e.g. bovine plasma). In the latter case, the non-primate mammalian plasma is preferably present in the coagulation control composition in an amount of not more than about 12% by volume, relative to total volume.

Claims

1. A coagulation control suitable for evaluating prothrombin time (PT) or activated partial thromboplastin time (APTT) assays, the coagulation control comprising

an abnormal plasma, and

an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa.

2. The coagulation control of

claim 1

wherein the anticoagulant is a glycosaminoglycan.

3. The coagulation control of

claim 1

wherein the anticoagulant is heparin.

4. The coagulation control of

claim 1

wherein the anticoagulant is a heparin derivative.

5. The coagulation control of

claim 1

wherein the anticoagulant is a heparin analog.

6. The coagulation control of

claim 1

wherein the abnormal plasma is a factor-deficient plasma deficient in one or more clotting factors selected from the group consisting of factors II, VII, IX and X.

7. The coagulation control of

claim 1

wherein the abnormal plasma is an activated plasma.

8. The coagulation control of

claim 1

wherein the abnormal plasma is an abnormal whole plasma.

9. The coagulation control of

claim 1

wherein the abnormal plasma is an abnormal plasma derivative.

10. A coagulation control suitable for evaluating prothrombin time (PT) or activated partial thromboplastin time (APTT) assays, the coagulation control comprising a solution comprising

a primate plasma,

a non-primate mammalian plasma, and

an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa, the concentration of anticoagulant ranging from about 0.01 U/ml to about 0.15 U/ml, where U is heparin-equivalent units.

11. The coagulation control of

claim 10

wherein the concentration of anticoagulant ranges from about 0.01 U/ml to about 0.1 U/ml.

12. The coagulation control of

claim 10

wherein the concentration of anticoagulant ranges from about 0.03 U/ml to about 0.07 U/ml.

13. The coagulation control of

claim 10

wherein the concentration of anticoagulant is about 0.05 U/ml.

14. The coagulation control of

claim 10

wherein the anticoagulant is a glycosaminoglycan.

15. The coagulation control of

claim 10

wherein the anticoagulant is heparin.

16. The coagulation control of

claim 10

wherein the anticoagulant is a heparin derivative.

17. The coagulation control of

claim 10

wherein the anticoagulant is a heparin analog.

18. The coagulation control of

claim 10

wherein the primate plasma or the non-primate mammalian plasma is whole plasma.

19. The coagulation control of

claim 10

wherein the primate plasma or the non-primate mammalian plasma is a plasma derivative.

20. The coagulation control of

claim 10

wherein the primate plasma is normal primate plasma.

21. The coagulation control of

claim 10

wherein the primate plasma is a factor-deficient primate plasma deficient in one or more clotting factors selected from the group consisting of factors II, VII, IX and X.

22. The coagulation control of

claim 10

wherein the primate plasma is an activated primate plasma.

23. The coagulation control of

claim 10

wherein the primate plasma is human plasma.

24. The coagulation control of

claim 10

wherein the non-primate mammalian plasma is bovine plasma.

25. The coagulation control of

claim 10

wherein the non-primate mammalian plasma is bovine plasma present in the solution in an amount ranging from about 0.5% to about 12% by volume.

26. The coagulation control of

claim 10

wherein

the primate plasma is human plasma present in the solution in an amount ranging from about 78% to about 99.5% by volume, and

the non-primate mammalian plasma is bovine plasma present in the solution in an amount ranging from about 0.5% to about 12% by volume.

27. The coagulation control of

claim 10

wherein the solution is reconstituted from a lyophilized composition.

28. The coagulation control of

claim 10

wherein the primate plasma is normal human plasma, the non-primate mammalian plasma is bovine plasma, and the anticoagulant is heparin or a heparin derivative.

29. The coagulation control of

claim 28

wherein

the normal human plasma is present in the solution in an amount ranging from about 88% to about 98% by volume,

the bovine plasma is present in the solution in an amount ranging from about 2% to about 4% by volume, and

the concentration of heparin or a heparin derivative ranges from about 0.01 U/ml to about 0.1 U/ml.

30. The coagulation control of

claim 28

wherein the concentration of heparin or heparin derivative ranges from about 0.01 U/ml to about 0.1 U/ml and the coagulation control further comprises an activated plasma.

31. The coagulation control of

claim 30

wherein the coagulation control has a prothrombin time ranging from about 9 seconds to about 14 seconds as determined using a thromboplastin reagent having an International Sensitivity Index (ISI) of about 2.

32. The coagulation control of

claim 30

wherein

the normal human plasma is present in the solution in an amount ranging from about 78% to about 99.5% by volume,

the bovine plasma is present in the solution in an amount ranging from about 0.5% to about 12% by volume, and

the activated plasma is activated human plasma present in the solution in an amount of not more than about 7% by volume.

33. The coagulation control of

claim 30

wherein

the solution further comprises a buffer,

the normal human plasma is present in the solution in an amount ranging from about 88% to about 95% by volume,

the bovine plasma is present in the solution in an amount ranging from about 2% to about 4% by volume, and

the activated plasma is a glass-wool-activated human plasma present in the solution in an amount ranging from about 3% to about 5% by volume.

34. The coagulation control of

claim 28

wherein the concentration of heparin or heparin derivative ranges from about 0.01 U/ml to about 0.1 U/ml, and the solution further comprises a factor-deficient human plasma deficient in one or more clotting factors selected from the group consisting of factors II, VII, IX and X.

35. The coagulation control of

claim 34

wherein the coagulation control has a prothrombin time ranging from about 15 seconds to about 25 seconds as determined using a thromboplastin reagent having an International Sensitivity Index (ISI) of about 2.

36. The coagulation control of

claim 34

wherein

the factor-deficient human plasma is present in the solution in an amount ranging from about 75% to about 85% by volume,

the bovine plasma is present in the solution in an amount ranging from about 0.5% to about 12% by volume, and

the normal human plasma is present in the solution in an amount ranging from about 0.5% to about 24.5% by volume.

37. The coagulation control of

claim 34

wherein

the solution further comprises a buffer,

the factor-deficient human plasma is present in the solution in an amount ranging from about 78% to about 82% by volume,

the bovine plasma is present in the solution in an amount ranging from about 2% to about 4% by volume, and

the normal human plasma is present in the solution in an amount ranging from about 11% to about 20% by volume.

38. The coagulation control of

claim 34

wherein the coagulation control has a prothrombin time ranging from about 25 seconds to about 33 seconds as determined using a thromboplastin reagent having an International Sensitivity Index (ISI) of about 2.

39. The coagulation control of

claim 34

wherein

the factor-deficient human plasma is present in the solution in an amount ranging from about 85% to about 95% by volume,

the bovine plasma is present in the solution in an amount ranging from about 0.5% to about 12% by volume, and

the normal human plasma is present in the solution in an amount ranging from about 0.5% to about 14.5% by volume.

40. The coagulation control of

claim 34

wherein

the solution further comprises a buffer,

the factor-deficient human plasma is present in the solution in an amount ranging from about 88% to about 92% by volume,

the bovine plasma is present in the solution in an amount ranging from about 2% to about 4% by volume, and

the normal human plasma is present in the solution in an amount ranging from about 1% to about 10% by volume.

41. A coagulation control suitable for evaluating prothrombin time (PT) or activated partial thromboplastin time (APTT) assays, the coagulation control comprising

primate plasma,

non-primate mammalian plasma, and

an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa, the concentration of anticoagulant ranging from about 0.1 U/g to about 0.18 U/g on a dry-weight basis where U is heparin-equivalent units.

42. The coagulation control of

claim 41

wherein the concentration of anticoagulant ranges from about 0.3 U/g to about 1.2 U/g.

43. The coagulation control of

claim 41

wherein the concentration of anticoagulant ranges from about 0.4 U/g to about 0.8 U/g.

44. The coagulation control of

claim 41

wherein the concentration of anticoagulant is about 0.6 U/g.

45. A coagulation control suitable for evaluating prothrombin time (PT) or activated partial thromboplastin time (APTT) assays, the coagulation control comprising

human plasma and non-primate mammalian plasma, the ratio of non-primate mammalian plasma to human plasma ranging from about 1:

200 to about 1;

5.

46. The coagulation control of

claim 45

wherein the ratio of non-primate mammalian plasma to human plasma ranges from about 1:

50 to about 1;

20.

47. The coagulation control of

claim 45

wherein the coagulation control is a solution.

48. The coagulation control of

claim 45

wherein the coagulation control is a solution comprising the non-primate mammalian plasma in an amount ranging from about 0.5% to about 12% by volume.

49. The coagulation control of

claim 45

wherein the coagulation control is a solution comprising the non-primate mammalian plasma in an amount ranging from about 2% to about 4% by volume.

50. The coagulation control of

claim 45

wherein the human plasma or the non-primate mammalian plasma is whole plasma.

51. The coagulation control of

claim 45

wherein the human plasma or the non-primate mammalian plasma is a plasma derivative.

52. The coagulation control of

claim 45

wherein the human plasma is normal human plasma.

53. The coagulation control of

claim 45

wherein the human plasma is a factor-deficient human plasma deficient in one or more clotting factors selected from the group consisting of factors II, VII, IX and X.

54. The coagulation control of

claim 45

wherein the human plasma is an activated human plasma.

55. The coagulation control of

claim 45

wherein the non-primate mammalian plasma is bovine plasma.

56. The coagulation control of

claim 45

wherein the non-primate mammalian plasma is bovine plasma present in an amount ranging from about 0.5% to about 12% by volume.

57. The coagulation control of

claim 45

wherein the non-primate mammalian plasma is bovine plasma present in an amount ranging from about 2% to about 4% by volume.

58. The coagulation control of

claim 45

wherein

the human plasma is present in an amount ranging from about 78% to about 99.5% by volume, and

the non-primate mammalian plasma is bovine plasma present in an amount ranging from about 0.5% to about 12% by volume.

59. The coagulation control of

claim 45

wherein the coagulation control is a lyophilized composition.

60. The coagulation control of

claim 45

wherein the coagulation control is a solution reconstituted from a lyophilized composition.

61. A method for preparing a coagulation control suitable for evaluating prothrombin time (PT) or activated partial thromboplastin time (APTT) assays, the method comprising

combining primate plasma, non-primate mammalian plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa to form a control solution having an anticoagulant concentration ranging from about 0.01 U/ml to about 0.15 U/ml, where U is heparin-equivalent units.

62. A coagulation control prepared according to the method of

claim 61

.

63. A method for preparing a coagulation control suitable for evaluating prothrombin time (PT) and activated partial thromboplastin time (APTT) assays, the method comprising

combining human plasma and non-primate mammalian plasma to form a control solution comprising non-primate mammalian plasma in an amount ranging from about 0.5% to about 12% by volume.

64. A coagulation control prepared according to the method of

claim 63

.

65. A method for quality control of a prothrombin time (PT) assay system, the method comprising

combining a PT reagent with a coagulation control to form an assay solution, the coagulation control comprising a plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa,

detecting clot formation in the assay solution, and

determining the time elapsed from formation of the assay solution to detection of clot formation in the assay solution.

66. A method for quality control of a prothrombin time (PT) or an activated partial thromboplastin time (APTT) assay system, the method comprising

combining a PT reagent or an APTT reagent with a coagulation control to form an assay solution, the coagulation control comprising an abnormal plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa,

detecting clot formation in the assay solution, and

determining the time elapsed from formation of the assay solution to detection of clot formation in the assay solution.

67. A method for quality control of a prothrombin time (PT) or an activated partial thromboplastin time (APTT) assay system, the method comprising

combining a PT reagent or an APTT reagent with a coagulation control solution to form an assay solution, the coagulation control solution comprising primate plasma, non-primate mammalian plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa, the concentration of anticoagulant in the coagulation control solution ranging from about 0.01 U/ml to about 0.15 U/ml, where U is heparin-equivalent units,

detecting clot formation in the assay solution, and

determining the time elapsed from formation of the assay solution to detection of clot formation in the assay solution.

68. A method for quality control of a prothrombin time (PT) or an activated partial thromboplastin time (APTT) assay, the method comprising

combining a PT reagent or an APTT reagent with a coagulation control to form an assay solution, the coagulation control comprising human plasma and non-primate mammalian plasma, the ratio of non-primate mammalian plasma to human plasma ranging from about 1:

200 to about 1;

5,

detecting clot formation in the assay solution, and

determining the time elapsed from formation of the assay solution to detection of clot formation in the assay solution.