Storage-stable cellular whole blood composition containing elevated amounts of D-dimer
The present invention provides a cellular whole-blood D-dimer composition for use with diagnostic test procedures for D-dimer, and a method of its preparation. The composition comprises human erythrocytes and processed plasma to which D-dimer, and stabilizers, and optionally antimicrobial agents, are added and can be used as a standard and control for D-dimer testing.
1. A liquid composition for use as a control for an assay of D-dimer in the plasma of a human patient of specified gender and age and for a specified assay method comprising:
a defibrinated plasma having a pH of about 4 to about 9 and a total protein content of proteins other than D-dimer of 0 to about 10 g/dL,
erythrocytes,
one or more stabilizers, and
D-dimer concentration that is elevated with respect to a normal concentration of endogenous D-dimer content for said specified gender and age and said specified assay method, wherein the D-dimer concentration of the liquid composition is above 200 ng/ml.
2. A composition according to claim 1 wherein the erythrocytes are mammalian erythrocytes.
3. A composition according to claim 1 wherein the erythrocytes are human erythrocytes.
4. A composition according to claim 1 wherein the erythrocytes are avian erythrocytes.
5. A composition according to claim 1 wherein the erythrocytes are selected from human, porcine, bovine, equine, caprine, ovine, chicken and turkey erythrocytes.
6. A composition according to claim 1 , wherein the D-dimer is selected from native, recombinant, and synthetic D-dimer.
7. A composition according to claim 1 , wherein the D-dimer is human D-dimer.
8. A composition according to claim 1 , wherein the plasma is selected from mammalian plasma and artificial plasma.
9. A composition according to claim 1 , wherein the plasma is mammalian plasma.
10. A composition according to claim 1 , wherein the plasma is human plasma.
11. A composition according to claim 1 , wherein the plasma is artificial plasma.
12. A composition according to claim 1 further comprising one or more antimicrobials.
13. A composition according to claim 12 wherein the one or more antimicrobials are selected from ciprofloxacin, chloramphenicol, gentamicin, amikacin, tobramycin, and amphotericin B.
14. A composition according to claim 1 wherein the one or more stabilizers comprise a protease inhibitor.
15. A composition according to claim 14 wherein the protease inhibitor comprises a serine protease inhibitor.
16. A composition according to claim 1 wherein the one or more stabilizers comprise a cross-linking agent.
17. A composition according to claim 16 wherein the cross-linking agent comprises formaldehyde or glutaraldehyde.
18. A composition according to claim 16 wherein the cross-linking agent is present in a concentration of from about 0.01% to about 2%.
19. A composition according to claim 1 wherein the one or more stabilizers comprise cyanide ion or ferricyanide ion.
20. A composition according to claim 19 wherein the one or more stabilizers comprise potassium cyanide.
21. A composition according to claim 1 comprising from about 0.1 to about 2.0 weight % of one or more stabilizers.
22. A composition according to claim 1 wherein the erythrocytes are lysable erythrocytes.
23. A composition according to claim 1 wherein the erythrocytes are not lysable.
24. A composition according to claim 1 having a pH of from about 5 to about 8.
25. A composition according to claim 1 having a pH of from about 6 to about 7.
26. A composition according to claim 1 comprising from about 1 to about 80 volume % plasma.
27. A composition according to claim 1 comprising from about 40 to about 60 volume % plasma.
28. A composition according to claim 1 comprising from about 10 to about 70 volume % erythrocytes.
29. A composition according to claim 1 comprising from about 30 to about 55 volume % erythrocytes.
30. A composition according to claim 1 having a protein content of from about 4 to about 8 g/dL.
31. A composition according to claim 1 having a protein content of from about 5 to about 7 g/dL.
32. A composition according to claim 1 further comprising one or more cardiac risk assessment or stroke and coagulation markers.
33. A composition according to claim 32 wherein the markers are selected from Troponin I, CKMB, BNP, hsCRP, homocysteine, HDL, LDL, cholesterol, and pro-BNP.
34. A composition according to claim 1 having a hematocrit value of from about 20 to about 60%.
35. A composition according to claim 1 having a hemoglobin concentration of from about 5 to about 17 g/dL.
36. A method for preparing a liquid composition for use as a control for an assay of D-dimer in the plasma of a human patient of specified gender and age and for a specified assay method comprising: combining
(a) a processed plasma comprising a defibrinated plasma having a pH of about 4 to about 9 and a total protein content of 0 to about 10 g/dL and
(b) erythrocytes and one or more stabilizers and subsequently adding
(c) D-dimer to elevate the D-dimer concentration of the liquid composition to above 200 ng/ml.
37. A method according to claim 36 wherein the erythrocytes are mammalian erythrocytes.
38. A method according to claim 36 wherein the erythrocytes are human erythrocytes.
39. A method according to claim 36 wherein the erythrocytes are avian erythrocytes.
40. A method according to claim 36 wherein the erythrocytes are selected from human, porcine, bovine, equine, caprine, ovine, chicken and turkey erythrocytes.
41. A method according to claim 36 wherein the D-dimer is selected from native, recombinant, and synthetic D-dimer.
42. A method according to claim 36 wherein the D-dimer is human D-dimer.
43. A method according to claim 36 wherein the plasma is selected from mammalian plasma and artificial plasma.
44. A method according to claim 36 wherein the plasma is human plasma.
45. A method according to claim 36 wherein the plasma is artificial plasma.
46. A method according to claim 36 wherein the composition further comprises one or more antimicrobials.
47. A method of monitoring a whole-blood based D-dimer assay comprising using a composition according to claim 1 as a control material.
48. A method according to claim 47 comprising using a series of two or more said compositions having different elevated amounts of D-dimer, as a control material.