Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations

Blood

Volumn 103, Issue 11, 2004, Pages 4173-4179

  Castoldi, Elisabetta ^a   Brugge, Jeroen M ^b   Nicolaes, Gerry A F ^b   Girelli, Domenico ^b   Tans, Guido ^b   Rosing, Jan ^b  

^a MAASTRICHT UNIVERSITY   (Netherlands)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; BLOOD CLOTTING FACTOR 5; BLOOD CLOTTING FACTOR 5 LEIDEN; BLOOD CLOTTING FACTOR 8A;

ACTIVATED PROTEIN C RESISTANCE; ADULT; ANTICOAGULATION; ARTICLE; CONTROLLED STUDY; FEMALE; GENE INACTIVATION; GENE MUTATION; HETEROZYGOTE; HIGH RISK PATIENT; HOMOZYGOTE; HUMAN; MAJOR CLINICAL STUDY; MALE; PARTIAL THROMBOPLASTIN TIME; PLASMA; PRIORITY JOURNAL; RISK FACTOR; VEIN THROMBOSIS;

EID: 2542486395     PISSN: 00064971     EISSN: None     Source Type: Journal    
DOI: 10.1182/blood-2003-10-3578     Document Type: Article

References (43)

1. Walker FJ, Fay PJ. Regulation of blood coagulation by the protein C system. FASEB J. 1992;6:2561-2567.
2. 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;269:31869-31880.
3. Fay PJ, Smudzin TM, Walker FJ. Activated protein C-catalyzed inactivation of human factor VIII and factor Villa. Identification of cleavage sites and correlation of proteolysis with cofactor activity. J Biol Chem. 1991;266:20139-20145.
4. Shen L, Dahlbäck B. Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor Villa. J Biol Chem. 1994;269:18735-18738.
5. Váradi K, Rosing J, Tans G, Schwarz HP. Influence of factor V and factor Va on APC-induced cleavage of human factor VIII. Thromb Haemost. 1995;73:730-731.
6. Lu D, Kalafatis M, Mann KG, Long GL. Comparison of activated protein C/protein S-mediated inactivation of human factor VIII and factor V. Blood. 1996;87:4708-4717.
7. Thorelli E, Kaufman RJ, Dahlbäck B. The C-terminal region of the factor V B-domain is crucial for the anticoagulant activity of factor V. J Biol Chem. 1998;273:16140-16145.
8. Thorelli E, Kaufman RJ, Dahlbäck B. Cleavage of factor V at Arg 506 by activated protein C and the expression of anticoagulant activity of factor V. Blood. 1999;93:2552-2558.
9. Westrick RJ, Sun H, Eitzman DT, et al. The factor V Leiden mutation results in the in vivo loss of a critical FV anticoagulant function [abstract]. Blood. 2002;100:127a.
10. 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 U S A. 1993;90:1004-1008.
11. Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 1993;342:1503-1506.
12. Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N EngI J Med. 1994;330:517-522.
13. de Visser MC, Rosendaal FR, Bertina RM. A reduced sensitivity for activated protein C in the absence of factor V Leiden increases the risk of venous thrombosis. Blood. 1999;93:1271-1276.
14. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64-67.
15. Nicolaes GA, Tans G, Thomassen MC, et al. Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C. J Biol Chem. 1995;270:21158-21166.
16. Kalafatis M, Bertina RM, Rand MD, Mann KG. Characterization of the molecular defect in factor VR506Q. J Biol Chem. 1995;270:4053-4057.
17. Váradi K, Rosing J, Tans G, Pabinger I, Keil B, Schwarz HP. Factor V enhances the cofactor function of protein S in the APC-mediated inactivation of factor VIII: influence of the factor VR506Q mutation. Thromb Haemost. 1996;76:208-214.
18. Lunghi B, Iacoviello L, Gemmati D, et al. Detection of new polymorphic markers in the factor V gene: association with factor V levels in plasma. Thromb Haemost. 1996;75:45-48.
19. Bernardi F, Faioni EM, Castoldi E, et al. A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood. 1997;90:1552-1557.
20. Hoekema L, Castoldi E, Tans G, et al. Functional properties of factor V and factor Va encoded by the R2-gene. Thromb Haemost. 2001;85:75-81.
21. Williamson D, Brown K, Luddington R, Baglin C, Baglin T. Factor V Cambridge: a new mutation (Arg306 → Thr) associated with resistance to activated protein C. Blood. 1998;91:1140-1144.
22. Chan WP, Lee CK, Kwong YL, Lam CK, Liang R. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood. 1998;91:1135-1139.
23. van der Neut Kolfschoten M, Dirven RJ, Tans G, Rosing J, Vos HL, Bertina RM. The activated protein C (APC)-resistant phenotype of APC cleavage site mutants of recombinant factor V in a reconstituted plasma model. Blood Coagul Fibrinolysis. 2002;13:207-215.
24. Norstrøm E, Thorelli E, Dahlbäck B. Functional characterization of recombinant FV Hong Kong and FV Cambridge. Blood. 2002;100:524-530.
25. Nicolaes GA, Dahlbäck B. Factor V and thrombotic disease: description of a janus-faced protein. Arterioscler Thromb Vasc Biol. 2002;22:530-538.
26. Faioni EM, Franchi F, Bucciarelli P, et al. Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood. 1999;94:3062-3066.
27. Folsom AR, Cushman M, Tsai MY, et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood. 2002;99:2720-2725.
28. Dahlbäck B. The discovery of activated protein C resistance. J Thromb Haemost. 2003;1:206-213.
29. Heeb MJ, Kojima Y, Greengard JS, Griffin JH. Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V. Blood. 1995;85:3405-3411.
30. Váradi K, Moritz B, Lang H, et al. A chromogenic assay for activated protein C resistance. Br J Haematol. 1995;90:884-891.
31. Govers-Riemslag JW, Castoldi E, Nicolaes GA, Tans G, Rosing J. Reduced factor V concentration and altered FV1/FV2 ratio do not fully explain R2-associated APC-resistance. Thromb Haemost. 2002;88:444-449.
32. Hoekema L, Rosing J, Tans G. An assay to quantify the two plasma isoforms of factor V. Thromb Haemost. 2000;84:1066-1071.
33. Seré KM, Janssen MP, Willems GM, Tans G, Rosing J, Hackeng TM. Purified protein S contains multimeric forms with increased APC-independent anticoagulant activity. Biochemistry. 2001;40:8852-8860.
34. Rosing J, Bakker HM, Thomassen MC, Hemker HC, Tans G. Characterization of two forms of human factor Va with different cofactor activities. J Biol Chem. 1993;268:21130-21136.
35. Simioni P, Scudeller A, Radossi P, et al. "Pseudo homozygous" activated protein C resistance due to double heterozygous factor V defects (factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: report of two cases belonging to two unrelated kindreds. Thromb Haemost. 1996;75:422-426.
36. Castoldi E, Govers-Riemslag JW, Pinotti M, et al. Co-inheritance of FV Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G>A (FVII Lazio) mutation. Blood. 2003;102:4014-4020.
37. Hemker HC, Wielders S, Kessels H, Béguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost. 1993;70:617-624.
38. Samama MS, Gouin-Thibault I, Trossaërt M, et al. Low levels of protein S activity in factor V depleted plasma used in APC resistance test. Thromb Haemost. 1998;80:715-716.
39. de Visser MCH, Guasch JF, Kamphuisen PW, Vos HL, Rosendaal FR, Bertina RM. The HR2 haplotype of factor V: effects on factor V levels, normalized activated protein C sensitivity ratios and the risk of venous thrombosis. Thromb Haemost. 2000;83:577-582.
40. Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci U S A. 1994;91:1396-1400.
41. Aparicio C, Dahlbäck B. Molecular mechanisms of activated protein C resistance. Properties of factor V isolated from an individual with homozygosity for the Arg506 to Gln mutation in the factor V gene. Biochem J. 1996;313:467-472.
42. Hemker HC, Béguin S. Phenotyping the clotting system. Thromb Haemost. 2000;84:747-751.
43. Castaman G, Faioni EM, Tosetto A, Bernardi F. The factor V HR2 haplotype and the risk of venous thrombosis: a meta-analysis. Haematologica. 2003;88:1182-1189.