Elevated levels of prothrombin activation fragment 1+2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency

Thrombosis and Haemostasis

Volumn 75, Issue 2, 1996, Pages 270-274

  Zöller, Bengt ^a   Holm, Johan ^a   Svensson, Peter ^a   Dahlbäck, Björn ^a,b  

^a LUND UNIVERSITY   (Sweden)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; ARGININE; BLOOD CLOTTING FACTOR 5; GLUTAMINE; PROTEIN S; PROTHROMBIN; THROMBIN; WARFARIN;

ADOLESCENT; ADULT; AGED; AMINO ACID SUBSTITUTION; ANTICOAGULATION; ARTICLE; CHILD; CONTROLLED STUDY; FEMALE; GENE MUTATION; HETEROZYGOTE; HUMAN; HYPERCOAGULABILITY; MAJOR CLINICAL STUDY; MALE; POINT MUTATION; PRIORITY JOURNAL; PROTEIN S DEFICIENCY; RISK; THROMBOSIS;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BIOLOGICAL MARKERS; CHILD; DISEASE SUSCEPTIBILITY; FACTOR V; FACTOR V DEFICIENCY; FEMALE; HUMANS; MALE; MIDDLE AGED; PEPTIDE FRAGMENTS; POINT MUTATION; PROTEIN S DEFICIENCY; PROTHROMBIN; THROMBOEMBOLISM; WARFARIN;

EID: 0029878085     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0038-1650259     Document Type: Article

References (46)

1. Dahlbäck B. The protein C anticoagulant system: inherited defects as basis for venous thrombosis. Thromb Res 1995; 77: 1-43.
2. Shen L, Dahlbäck B. Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa. J Biol Chem 1994; 269: 18735-8.
3. Marlar RA, Montgomery RR, Madden RM. Homozygous protein C deficiency. In: Protein C and related proteins. Bertina RM, eds. Churchill Livingstone, Edinburgh, 1988; pp 182-95.
4. Allaart CF, Poort SR, Rosendaal FR, Reitsma PH, Bertina RM, Briët E. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 1993; 341: 134-8.
5. Engesser L, Broekmans AW, Briët E, Brommer EJP, Bertina RM. Hereditary protein S deficiency: Clinical manifestations. Ann Intern Med 1987; 106: 677-82.
6. Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518-23.
7. Zoller B, Garcia de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85: 3524-31.
8. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
9. Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-21.
10. Koster T, Rosendaal FR, de Ronde F, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503-6.
11. Faioni EM, Franchi F, Asti D, Sacchi E, Beraardi F, Mannucci PM. Resistance to activated protein C in nine thrombophilic families: Interference in a protein S functional assay. Thromb Haemost 1993; 70: 1067-71.
12. Halbmayer WM, Haushofer A, Schön R, Fischer M. The prevalence of poor anticoagulant response to activated protein C (APC resistance) among padents suffering from stroke or venous thrombosis and among healthy subjects. Blood Coagul Fibrinol 1994; 5: 51-7.
13. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995; 332: 912-7.
14. Beuchamp NJ, Daly ME, Hampton KK, Cooper PC, Preston FE, Peake IR. High prevalence of mutation in the factor V gene within the U.K. population; relationship to activated protein C resistance and familial thrombosis. Br J Haematol 1994; 88: 219-22.
15. Griffin JH, Evatt B, Wideman C, Fernández JA. Anticoagulant protein C pathway defective in a majority of thrombophilic patients. Blood 1993; 82: 1989-93.
16. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
17. Greengard JS, Sun X, Xu X, Fernandez JA, Griffin JH, Evatt BL. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994; 343: 1362-3.
18. Voorberg J, Roelse J, Koopman R, Büller H, Berends F, ten Cate JW, Mertens K, van Mourik JA. Association of idiopathic thromboembolism with single point mutation at Arg506 of factor V. Lancet 1994; 343: 1535-6.
19. Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-8.
20. Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-4.
21. Sun X, Evatt BL, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120-5.
22. Kalafatis M, Rand MD, Mann KG. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J Biol Chem 1994; 269: 31869-80.
23. Heeb MJ, Kojima Y, Greengard JS, Griffin JH, Activated protein C resistance: Molecular mechanisms based on studies using purified Gln506-factor V. Blood 1995; 85: 3405-11.
24. Kalafatis M, Bertina RM, Rand MD, Mann KG. Characterization of the molecular defect in factor VR506Q. J Biol Chem 1995; 270: 4053-7.
25. 506 to Gln mutation in the factor V gene. Biochem J (In press).
26. Griffin JH, Heeb MJ, Kojima Y, Fernandez JA, Kojima K, Hackeng TM, Greengard JS. Activated protein C resistance: molecular mechanisms. Thromb Haemost 1995; 74: 444-8.
27. 1+2) during the clotting of blood and plasma. J Clin Invest 1977; 60: 1410-8.
28. Bauer KA. New markers for in vivo coagulation. Current Opinion in Hematology 1994; 1: 341-6.
29. Mannucci PM. Mechanisms, markers and management of coagulation activation. British Medical Bulletin 1994; 50: 851-70.
30. Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. J Clin Invest 1987; 80: 1527-34.
31. Bauer KA, Broekmans AW, Bertina RM, Conard J, Horellou MH, Samama MM, Rosenberg RD. Hemostatic enzyme generation in the blood of patients with hereditary protein C deficiency. Blood 1988; 71: 1418-26.
32. Mannucci PM, Tripodi A, Bottasso B, Baudo F, Finazzi G, De Stefano V, Palareti G, Manotti C, Mazzucconi G, Castaman G. Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes. Thromb Haemost 1992; 67: 200-2.
33. Catto A, Carter A, Ireland H, Bayston TA, Philippou H, Barrett J, Lane DA, Grant PJ. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol 1995; 15: 783-5.
34. Kienast J, Thompson SG, Raskino C, Pelzer H, Fechtrup C, Ostermann H. Prothrombin activation fragment 1+2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. Thromb Haemost 1993; 70: 550-3.
35. Merlini, PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannueci PM, Rosenberg RD. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90: 61-8.
36. Bauer KA, Goodman TL, Kass BL, Rosenberg RD. Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency. J Clin Invest 1985; 76: 826-36.
37. Bauer KA, Barzegar S, Rosenberg RD. Influence of anticoagulants used for blood collection on plasma prothrombin fragments F1+2 measurements. Thrombosis Res 1991; 63: 617-28.
38. Demers C, Ginsberg JS, Henderson P, Ofosu FA, Weitz JI, Blajchman MA. Measurement of markers of activated coagulation in antithrombin III deficient subjects. Thromb Haemost 1992; 67: 542-4.
39. Holm J, Bemtorp E, Carlsson R, Erhardt L. Low-dose warfarin decreases coagulability without affecting prothrombin complex activity. J Intern Med 1993; 234: 303-8.
40. Conway EM, Bauer KA, Barzegar S, Rosenberg RD. Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diatheses. J Clin Invest 1987; 80: 1535-44.
41. Greengard JS, Eichinger S, Griffin JH, Bauer KA. Brief report: variability of thrombosis among homozygous siblings with resistance to activated protein C due to an Arg→Gln mutation in the gene for factor V. N Engl J Med 1994; 331: 1559-62.
42. Martinelli I, Faioni EM, Monzani ML, Mannucci PM. Inherited resistance to actvated protein C (APC): Clinical and laboratory features. Blood 1994; 84 (Suppl 1): 84a (abstract).
43. Koeleman BPC, van Rumpf D, Hamulyák K, Reitsma PH, Bertina RM. Factor V Leiden. An additional risk factor for thrombosis in protein S deficient families? Thromb Haemost 1995; 74: 580-3.
44. Malm J, Laurell M, Dahlbäck B. Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 1988; 68: 437-43.
45. Dahlbäck B. Physiological anticoagulation. Inherited resistance to activated protein C and venous thromboembolism. J Clin Invest 1994; 94: 923-7.
46. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous forfactor V Leiden (activated protein C Resistance). Blood 1995; 85: 1504-8.