Activated protein C resistance due to a common factor V gene mutations is a major risk factor for venous thrombosis

Annual Review of Medicine

Volumn 48, Issue , 1997, Pages 45-58

  Zoller B ^a   Hillarp, A ^a   Berntorp, E ^a   Dahlback B ^a  

^a LUND UNIVERSITY   (Sweden)

Author keywords

Blood coagulation; Genetics; Protein C; Protein S; Thrombophilia

Indexed keywords

ACTIVATED PROTEIN C; ANTITHROMBIN III; ARGININE; BLOOD CLOTTING FACTOR 5; GLUTAMINE; PROTEIN C; PROTEIN S;

ETHNIC GROUP; GENE FREQUENCY; GENE MUTATION; GENETIC RISK; HUMAN; HYPERCOAGULABILITY; LABORATORY TEST; POINT MUTATION; PRIORITY JOURNAL; REVIEW; RISK FACTOR; THROMBOPHILIA; THROMBOSIS PREVENTION; VEIN THROMBOSIS;

DNA MUTATIONAL ANALYSIS; FACTOR V; GENETIC PREDISPOSITION TO DISEASE; GENETICS, POPULATION; HUMANS; OLIGOPEPTIDES; PROTEIN C; RISK FACTORS; THROMBOPHLEBITIS;

EID: 0031040293     PISSN: 00664219     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.med.48.1.45     Document Type: Review

References (103)

1. Furie B, Furie BC. 1988. The molecular basis of blood coagulation. Cell 53:505-18
2. Nemerson Y. 1989. Tissue factor and hemostasis. Annu. Rev. Biochem. 71:1-8
3. Davie EW. 1995. Biochemical and molecular aspects of the coagulation cascade. Thromb. Haemost. 74:1-6
4. Esmon CT, Schwarz HP. 1995. An update on clinical and basic aspects of the protein C anticoagulant pathway. Trends Cardiovasc. Med. 5:141-48
5. Dahlbäck B. 1995. The protein C anticoagulant system: inherited defects as basis for venous thrombosis. Thromb. Res. 77: 1-43
6. Shen L, Dahlbäck B. 1994. Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa. J. Biol. Chem. 269:18735-38
7. Váradi K, Rosing J, Tans G, Schwarz HP. 1995. Influence of factor V and factor Va on APC-induced cleavage of human factor VIII. Thromb. Haemost. 73:730-31
8. Marlar RA, Neumann A. 1990. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin. Thromb. Hemost. 16:299-309
9. Dahlbäck B, Carlsson M, Svensson PJ. 1993. 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 90:1-8
10. Dahlbäck B, Hildebrand B. 1994. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc. Natl. Acad. Sci. USA 81:1396-400
11. Bertina RM, Koeleman BPC, Koster T, et al. 1994. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64-67
12. Sun X, Evatt BL, Griffin JH. 1994. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 83: 3120-25
13. Zöller B, Dahlbäck B. 1994. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 343:1536-38
14. Greengard JS, Sun X, Xu X, Femandez JA, et al. 1994. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 343:1362-63
15. Voorberg J, Roelse J, Koopman R, et al. 1994. Association of idiopathic thromboembolism with single point mutation at Arg506 of factor V. Lancet 343:1535-36
16. Kalafatis M, Bertina RM, Rand MD, Mann KG. 1995. Characterization of the molecular defect in factor VR506Q. J. Biol. Chem. 270:4053-57
17. Heeb MJ, Kojima Y, Greengard JS, Griffin JH. 1995. Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V. Blood 85: 3405-11
18. R506Q by activated protein C. J. Biol. Chem. 270: 21158-66
19. R506Q by activated protein C. J. Biol. Chem. 270:27852-58
20. Kalafatis M, Rand MD, Mann KG. 1994. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J. Biol. Chem. 269:31869-80
21. Zöller B, Svensson PJ, He X, Dahlbäck B. 1994. Identification of the same factor V gene mutation in 47 out of 50 thrombosisprone families with inherited resistance to activated protein C. J. Clin. Invest. 94: 2521-24
22. Zöller B, Holm J, Svensson PJ, Dahlbäck B. 1996. Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with inherited APC-resistance and/ or protein S deficiency. Thromb. Haemost. 75:270-74
23. Simioni P, Scarano L, Gavasso S, et al. 1996. Prothrombin fragment 1 + 2 and thrombin-antithrombin complex levels in patients with inherited APC-resistance due to factor V Leiden mutation. Br. J. Haematol. 92:435-41
24. Liu XY, Nelson D, Grant C, et al. 1995. Molecular detection of a common mutation in coagulation factor V causing thrombosis via hereditary resistance to activated protein C. Diagn. Mol. Pathol. 4:191-97
25. Hampton KK, Path MRC, Preston FE, Greaves M. 1994. Resistance to activated protein C. N. Engl. J. Med. 331:130
26. Halbmayer WM, Haushofer A, Schön R, Fischer M. 1994. Influence of lupus anticoagulant on a commercial available kit for APC-resistance. Thromb. Haemost. 72: 643-51
27. Gschwandtner ME, Lechner K, Pabinger I. 1995. Erroneously low APC ratio in patients with lupus anticoagulant. Ann. Hematol. 70:169-70
28. Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. 1995. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb. Haemost. 74:449-53
29. Svensson PJ, Dahlbäck B. 1994. Resistance to activated protein C as a basis for venous thrombosis. N. Engl. J. Med. 330: 517-21
30. Dahlbäck B. 1995. Resistance to activated protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb. Haemost. 73: 739-42
31. de Ronde H, Bertina RM. 1994. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb. Haemost. 72:880-86
32. Trossaërt M, Conard J, Horellou NM, et al. 1994. Modified APC resistance assay for patients on oral anticoagulants. Lancet 344: 1709
33. Tosetto A, Rodeghiero F. 1995. Diagnosis of APC resistance in patients on oral anticoagulant therapy. Thromb. Haemost. 73: 732-33
34. Jorquera JI, Montoro JM, Fernández MA, et al. 1994. Modified test for activated protein C resistance. Lancet 344:1162-63
35. Dahlbäck B, Hillarp A, Rosen S, Zöller B. 1996. Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Ann. Hematol. 72:166-76
36. Trossaert M, Conard J, Horellou NM, et al. 1996. The modifed APC resistance test in the presence of factor V deficient plasma can be used in patients without oral anticoagulation. Thromb. Haemost. 75:521-22
37. Engel H, Zwang L, van Vliet FMDM, et al. 1996. Phenotyping and genotyping of coagulation factor V Leiden. Thromb. Haemost. 75:267-69
38. van de Locht LTF, Kuypers AWHM, Verbruggen BW, et al. 1995. Semiautomated detection of the factor V mutation by allele specific amplification and capillary electrophoresis. Thromb. Haemost. 74:1276
39. Gandrille S, Alhenc Gelas M, Aiach M. 1995. A rapid screening method for the factor V Arg506 → Gln mutation. Blood Coagul. Fibrinolysis. 6:245-48
40. Kirschbaum N-E, Foster PA. 1995. The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance. Thromb. Haemost. 74: 874-78
41. Bellissimo DB, Kirschbaum NE, Foster PA. 1996. Improved method for factor V Leiden typing by PCR-SSP. Thromb. Haemost. 75:520
42. Rees DC, Cox M, Clegg JB. 1996. Detection of the factor V Leiden mutation using whole blood PCR. Thromb. Haemost. 75: 520-21
43. Griffin JH, Evatt BL, Wideman C, Fernandez JA. 1993. Anticoagulant protein C pathway defective in a majority of thrombophilic patients. Blood 82:1989-93
44. Koster T, Rosendaal FR, de Ronde F, et al. 1993. Venous thrombosis due to poor response to activated protein C: Leiden thrombophilia study. Lancet 342:1503-6
45. Faioni EM, Franchi F, Asti D, et al. 1993. Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay. Thromb. Haemost. 70:1067-71
46. Halbmayer WM, Haushofer A, Schön R, Fischer M. 1994. The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects. Blood Coagul. Fibrinolysis. 5:51-57
47. Cadroy Y, Sié P, Boncu B. 1994. Frequency of a defective response to activated protein C in patients with a history of venous thrombosis. Blood 83:2008-9
48. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. 1995. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 85:1504-8
49. Borell M, Vallvé C, Urrutia T, et al. 1994. APC resistance in patients with thrombophilia. Haemostasis 24(Suppl. 1):145 (Abstr.)
50. Rees DC, Cox M, Clegg J-B. 1995. World distribution of factor V Leiden. Lancet 346: 1133-34
51. Ridker PM, Hennekens CH, Lindpaintner K, et al. 1995. 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. 332:912-17
52. Zöller B, et al. 1996. High prevalence of the FUR506Q mutation causing 4PC resistance in a reigion of southern Sweden with a high incidence of venous thrombosis. Thromb. Res. In press
53. Holm J, Zöller B, Berntorp E, et al. 1996. Prevalence of factor V gene mutation among myocardial infarction patients and healthy controls higher in Sweden than in other countries. J. Intern. Med. 239: 221-26
54. Cox M, Rees DC, Martinsson JJ, Clegg JB. 1996. Evidence for a single origin of factor V Leiden. Br. J. Haematol. 92:1022-25
55. Thaler E, Lechner K. 1981. Antithrombin M deficiency and thromboembolism. Clin. Haematol. 10:369-90
56. Engesser L, Brockmans AW, Bridt E, et al. 1987. Hereditary protein S deficiency: clinical manifestations. Ann. Intern. Med. 106:677-82
57. Allaart RC, Poort SR, Rosendaal FR, et al. 1993. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 341:134-38
58. Munkvad S, Jörgensen M. 1996. Resistance to activated protein C: a common anticoagulant deficiency in patients with venous leg ulceration. Br. J. Dermatol. 134: 296-98
59. Makris M, Bardhan G, Preston FE. 1996. Warfarin induced skin necrosis associated with activated protein C resistance. Thromb. Haemost. 75:523-24
60. Mambrini P, Mallet D, O'Callaghan T, et al. 1996. Budd-Chiari syndrome and activated protein C resistance. J. Hepatol. 24:246
61. Gardyn J, Sorkin P, Kluger Y, et al. 1995. Heparin-induced thrombocytopenia and fatal thrombosis in a patient with activated protein C resistance. Am. J. Hematol. 50: 2925
62. Brenner B, Lanir N, Thaler I. 1996. HELLP syndrome associated with factor V R506. Br. J. Haematol. 92:999-1001
63. Lindblad B, Svensson PJ, Dahlbäck B. 1994. Arterial and venous thromboembolism with fatal outcome in a young man with inherited resistance to activated protein C. Lancet 343:917
64. Holm J, Zöller B, Svensson PJ, et al. 1994. Myocardial infarction associated with homozygous resistance to activated protein C. Lancet 344:952-53
65. Simioni P, de Rode H, Prandoni P, et al. 1995. Ischemic stroke in young patients with activated protein C resistance. A report of three cases belonging to three different kindreds. Stroke 26:885-90
66. Ganesan V, Kelsey H, Cookson J, et al. 1996. Activated protein C resistance in childhood stroke. Lancet 347:260
67. März W, Seydewitz H, Winkelmann B, et al. 1995. Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease. Lancet 345:526-27
68. Emmerich J, Poitier O, Evans A, et al. 1995. Myocardial infarction, Arg506 to Gln factor V mutation, and activated protein C resistance. Lancet 345:321
69. Catto A, Carter A, Ireland H, et al. 1995. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler. Thromb. Vasc. Biol. 15:783-85
70. Forsyth PD, Dolan G. 1995. Activated protein C resistance in cases of cerebral infarction. Lancet 345:795
71. Eritsland J, Gjonnes G, Sandset PM, et al. 1995. Activated protein C resistance and graft occlusion after coronary artery bypass surgery. Thromb. Res. 79:223-26
72. Biasiutti FD, Merio C, Furlan M, et al. 1995. No association of APC-resistance with myocardial infarction. Blood. Coagul. Fibrinolysis. 6:456-59
73. van Bockxmeer FM, Baker RI, Taylor RR. 1995. Premature ischaemic heart disease and the gene for coagulation factor V. Nature 1:185
74. Cushman M, Bhushan F, Bovill E, Tracy R. 1994. Plasma resistance to activated protein C in venous and arterial thrombosis. Thromb. Haemost. 72:647
75. Press RD, Liu XY, Beamer N, Coull BM. 1996. Ischemic stroke in the elderly. Role of the corrunon factor V mutation causing resistance to activated protein C. Stroke 27:44-48
76. Lalouschek W, Suess E, Aull E, et al. 1996. Clinical and laboratory data in heterozygous factor V Leiden mutation positive versus negative patients with TIA and minor stroke. Stroke 26:1963-64
77. Greengard JS, Etchinger S, Griffin JH, Bauer KA. 1994. 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. 331:1559-62
78. Mari D, Mannucci PM, Duca F, et al. 1996. Mutant factor V (Arg506Gln) in healthy centenarians. Lancet 347:1044
79. Samama MM, Trossaert M, Horellou MH, et al. 1995. Risk of thrombosis in patients homozygous for factor V Leiden. Blood 86:4700-2
80. Mandel H, Brenner B, Berant M, et al. 1996. Coexistence of hereditary homocystinuria and factor V Leiden-effect on thrombosis. N. Engl. J. Med. 334:763-68
81. Koeleman BPC, Reitsma PH, Allaart RC, Bertina RM. 1994. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 84:1031-35
82. Gandrille S, Greengard JS, Alhenc Gelas M, et al. 1995. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. Blood 86:219-24
83. Zöller B, He X, Dahlbäck B. 1995. Homozygous APC-resistance combined with protein S deficiency in a young boy with severe thrombotic disease. Thromb. Haemost. 73:743-75
84. Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. 1995. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 85:3518-23
85. Koeleman BPC, van Rumpf D, Hamulyák K, et al. 1995. Factor V Leiden. An additional risk factor for thrombosis in protein S deficient families? Thromb. Haemost. 74: 580-83
86. Duchemin J, Borg JY, Borgel D, et al. 1996. Five novel mutations of the protein S active gene (PROS 1) in 8 Norman families. Thromb. Haemost. 75:437-44
87. van Boven HH, Reitsma PH, Rosendaal FR, et al. 1996. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb. Haemost. 75:417-21
88. De Stefano V, Mastrangelo S, Paciaroni K, et al. 1995. Thrombotic risk during pregnancy and puerperium in women with APC-resistance - effective subcutaneous heparin prophylaxis in a pregnant patient. Thromb. Haemost. 74:793-94
89. Eschwege V, Robert A. 1996. Strikes in French public transport and resistance to activated protein C. Lancet 347:206
90. Hellgren M, Svensson PJ, Dahlbäck B. 1995. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am. J. Obstet. Gynecol. 173:210-13
91. 506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br. J. Haematol. 92:473-78
92. Vandenbroucke JP, Koster T, Bridt E, et al. 1994. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 344: 1453-57
93. Bloemenkamp KWM, Rosendaal FR, Heimerhorst FM, et al. 1995. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 346:1593-96
94. Rai R, Regan L, Hadley E, et al. 1996. Second-trimester pregnancy loss is associated with activated protein C resistance. Br. J. Haematol. 92:489-90
95. Fauno P, Ravn BB, Lassen JF, et al. 1995. Association between activated protein C resistance and postoperative deep vein thrombosis. Thromb. Haemost. 73:1371 (Abstr.)
96. Bauer KA. 1995. Management of patients with hereditary defects predisposing to thrombosis including pregnant women. Thromb. Haemost. 74:94-100
97. Malm J, Laurell M, Nilsson IM, Dahlbäck B. 1992. Thromboembolic disease critical evaluation of laboratory investigation. Thromb. Haemost. 68:7-13
98. Sarasin F, Bounameaux H. 1994. Duration of oral anticoagulant therapy after proximal deep vein thrombosis: a decision analysis. Thromb. Haemost. 71:286-91
99. Rintelen C, Pabinger P, Knöbl P, et al. 1996. Probability of recurrence of thrombosis in patients with and without factor V Leiden. Thromb. Haemost. 75:229-32
100. Ridker PM, Miletich JP, Stampfer MJ, et al. 1995. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 92:2800-2
101. De Stefano V, Leone G, Mastrangelo S, et al. 1994. Clinical manifestations and management of inherited thrombophilia; retrospective analysis and follow-up after diagnosis of 238 patients with congenital deficiency of antithrombin III, protein C, protein S. Thromb. Haemost. 72:352-58
102. Rosendaal FR. 1996. Oral contraceptives and screening for factor V Leiden. Thromb. Haemost. 75:524-25
103. Zöller B, Holm J, Dahlbäck B. 1996. Resistance to activated protein C due to a factor V gene mutation. The most common inherited risk factor of thrombosis. Trends Cardiovasc. Med. 6:45-53