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Research Article| Volume 16, ISSUE 1, P169-186, March 1996

Resistance to Activated Protein C and A Novel Factor V Gene Mutation

  • Karl V. Voelkerding
    Correspondence
    Address reprint requests to: Karl V. Voelkerding, MD, Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, D4/212 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792-2472
    Affiliations
    From the Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School; and the Molecular Diagnostics Laboratory and Transfusion Services, University of Wisconsin Hospital and Clinics, Madison, Wisconsin
    Search for articles by this author
DOI:https://doi.org/10.1016/S0272-2712(18)30293-2
Resistance to Activated Protein C and A Novel Factor V Gene Mutation
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      A novel mutation in the factor V gene of the blood coagulation cascade has been identified recently. The mutation confers a lifelong hypercoagulable state, and carriers of the mutation have an approximate eightfold increase in relative risk for the development of venous thrombosis. Carriers of the mutation manifest a laboratory coagulation defect termed resistance to activated protein C (APC). This article reviews the discovery of APC resistance, the identification of the factor V gene mutation, and laboratory approaches to their diagnosis.
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      References

        • Alhenic-Gelas M.
        • Gandrille S.
        • Aubrey M.L.
        • et al.
        Unexplained thrombosis and factor Leiden.
        Lancet. 1994; 344: 555-556
        • Allaart C.F.
        • Briet E.
        Familial venous thrombophilia.
        in: Bloom AL Forbes CD Thomas DP Haemostasis and Thrombosis. ed 3. Churchill-Livingstone, New York1994: 1349-1360
        • Beauchamp N.J.
        • Daly M.E.
        • Cooper P.C.
        • et al.
        Rapid two-stage PCR for detecting factor G1691A mutation.
        Lancet. 1994; 344: 694-695
        • Beauchamp N.J.
        • Daly M.E.
        • Hampton K.K.
        • et al.
        High prevalence of a mutation in the factor V gene within the UK population: Relationship to activated protein C resistance and familial thrombosis.
        Br J Haematol. 1994; 88: 219-222
        • Bertina R.M.
        • Koeleman B.P.C.
        • Koster T.
        • et al.
        Mutation in blood coagulation factor V associated with resistance to activated protein C.
        Nature. 1994; 369: 64-67
        • Bertina R.M.
        • Reitsma P.H.
        • Rosendaal F.R.
        • et al.
        Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis.
        Thromb Haemost. 1995; 74: 449-453
        • Cadroy Y.
        • Sie P.
        • Boneu B.
        Frequency of a defective response to activated protein C in patients with a history of venous thrombosis.
        Blood. 1994; 83: 2008-2009
        • Cripe L.D.
        • Moore K.D.
        • Kane W.H.
        Structure of the gene for human coagulation factor V.
        Biochemistry. 1992; 31: 3777-3785
        • Culver D.
        • Crawford J.S.
        • Gardiner J.H.
        • et al.
        Venous thrombosis after fractures of the upper end of the femur: A study of incidence and site.
        J Bone Joint Surg Br. 1970; 52: 61-69
        • Dahlbäck B.
        Familial thrombophilia associated with resistance to activated protein C is due to a deficiency of a novel protein C cofactor [abstract].
        Thromb Haemost. 1993; 69: 978
        • Dahlbäck B.
        Physiological anticoagulation: Resistance to activated protein C and venous thromboembolism.
        J Clin Invest. 1994; 94: 923-927
        • Dahlbäck B.
        Inherited thrombophilia: Resistance to activated protein C as a pathogenic factor of venous thromboembolism.
        Blood. 1995; 85: 607-614
        • Dahlbäck B.
        Molecular genetics of thrombophilia: Factor V gene mutation causing resistance to activated protein C as a basis of the hypercoagulable state.
        J Lab Clin Med. 1995; 125: 566-571
        • Dahlbäck B.
        New molecular insights into the genetics of thrombophilia. Resistance to activated protein C caused by Arg506 to Gin mutation in Factor V as a pathogenic risk factor for venous thrombosis.
        Thromb Haemost. 1995; 74: 139-148
        • Dahlbäck B.
        • Carlsson M.
        • Svensson P.J.
        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: 1004-1008
        • 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 USA. 1994; 91: 1396-1400
        • Gerstman B.B.
        • Piper J.M.
        • Tomita D.K.
        • et al.
        Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease.
        Am J Epidemiol. 1991; 133: 32-37
        • Goldhaber S.Z.
        Epidemiology of pulmonary embolism and deep vein thrombosis.
        in: Bloom AL Forbes CD Thomas DP Haemostasis and Thrombosis. ed 3. Churchill-Livingstone, New York1994: 1327-1333
        • Greengard J.S.
        • Sun X.
        • Xu X.
        • et al.
        Activated protein C resistance caused by Arg506Gln mutation in factor Va.
        Lancet. 1994; 343: 1361-1362
        • Griffin J.H.
        • Evatt B.
        • Wideman C.
        • et al.
        Anticoagulant protein C pathway defective in majority of thrombophilic patients.
        Blood. 1993; 82: 1989-1993
        • Griffin J.H.
        • Heeb M.J.
        • Kojima Y.
        • et al.
        Activated protein C resistance: Molecular mechanisms.
        Thromb Haemost. 1995; 74: 444448
        • Heeb M.J.
        • Kojima Y.
        • Greengard J.S.
        • et al.
        Activated protein C resistance: Molecular mechanisms based on studies using purified Gln506-factor V.
        Blood. 1995; 85: 3405-3411
        • Heijboer H.
        • Brandjes D.P.M.
        • Buller H.R.
        • et al.
        Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis.
        N Engl J Med. 1990; 323: 1512-1516
        • Holm J.
        • Zoller B.
        • Svensson P.J.
        • et al.
        Myocardial infarction associated with homozygous resistance to activated protein C.
        Lancet. 1994; 344: 952-953
        • Jenny R.J.
        • Pittman D.D.
        • Toole J.J.
        • et al.
        Complete cDNA and derived amino acid sequence of human factor V.
        Proc Natl Acad Sci USA. 1987; 84: 4846-4850
        • Johansson K.
        • Lindberg K.
        • Menschik M.
        • et al.
        Evaluation of a kit for detection of resistance in plasma towards activated protein C activity in a modified APTT assay [abstract].
        Thromb Haemost. 1993; 69: 1120
        • Kalafatis M.
        • Bertina R.M.
        • Rand M.D.
        • et al.
        Characterization of the molecular defect in factor VR506Q.
        J Biol Chem. 1995; 270: 40534057
        • Kirschbaum N.E.
        • Foster P.A.
        The polymerase chain reaction with sequence specific primers for the detection of the factor V mutation associated with activated protein C resistance.
        Thromb Haemost. 1995; 74: 874-878
        • Koeleman B.P.C.
        • Reitsma P.H.
        • Allaart C.F.
        • et al.
        Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.
        Blood. 1994; 84: 1031-1035
        • Koster T.
        • Rosendaal F.R.
        • de Ronde H.
        • et al.
        Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study.
        Lancet. 1993; 342: 1503-1506
        • Kudsk K.A.
        • Fabian T.C.
        • Baum S.
        • et al.
        Silent deep vein thrombosis in immobilized multiple trauma patients.
        Am J Surg. 1989; 158: 515-519
        • Lindblad B.
        • Svensson P.J.
        • Dahlbäck B.
        Arterial and venous thromboembolism with fatal outcome and resistance to activated protein C.
        Lancet. 1994; 343: 917
        • Malm J.
        • Laurell M.
        • Nilsson I.M.
        • et al.
        Thromboembolic disease-critical evaluation of laboratory investigation.
        Thromb Haemost. 1992; 68: 7-13
        • Miletich J.P.
        • Prescott S.M.
        • White R.
        • et al.
        Inherited predisposition to thrombosis.
        Cell. 1993; 72: 477-480
        • Reitsma P.H.
        • Poort S.R.
        • Bernardi F.
        • et al.
        Protein C deficiency: A database of mutations.
        Thromb Haemost. 1993; 69: 77-84
        • Ridker P.M.
        • Hennekens C.H.
        • Lindpaintner K.
        • et al.
        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: 912-917
        • Rosen S.
        • Johansson K.
        • Lindberg K.
        • et al.
        Multicenter evaluation of a kit for activated protein C resistance on various coagulation instruments using plasmas from healthy individuals.
        Thromb Haemost. 1994; 72: 255-260
        • Rosendaal F.R.
        • Koster T.
        • Vandenbroucke J.P.
        • et al.
        High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance).
        Blood. 1995; 85: 1504-1508
        • 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
        • Sun X.
        • Evatt B.
        • Griffin J.H.
        Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia.
        Blood. 1994; 83: 3120-3125
        • Svensson P.J.
        • Dahlbäck B.
        Twenty novel families with thrombophilia and inherited resistance to activated protein C [abstract].
        Thromb Haemost. 1993; 69: 1252
        • Svensson P.J.
        • Dahlbäck B.
        Novel mechanism for thrombosis characterized by a poor anticoagulant response to activated protein C constitutes a major cause of thrombophilia [abstract].
        Thromb Haemost. 1993; 69: 999
        • Svensson P.J.
        • Dahlbäck B.
        Resistance to activated protein C as a basis for venous thrombosis.
        N Engl J Med. 1994; 330: 517-521
        • Tabemero M.D.
        • Tomas J.F.
        • Alberca I.
        • et al.
        Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis.
        Am J Hematol. 1991; 36: 249-254
        • The Le D.
        • Griffin J.H.
        • Greengard J.S.
        • et al.
        Use of a generally applicable tissue factor-dependent factor V assay to detect activated protein C-resistant factor Va in patients receiving warfarin and in patients with a lupus anticoagulant.
        Blood. 1995; 85: 1704-1711
        • Thomas D.P.
        Pathogenesis of venous thrombosis.
        in: Bloom AL Forbes CD Thomas DP Thrombosis and Haemostasis. ed 3. Churchill-Livingstone, New York1994: 1335-1347
        • Tuddenham E.G.D.
        • Cooper D.N.
        The molecular genetics of haemostasis and its inherited disorders. Oxford University Press, Oxford1994
        • Vandenbroucke J.P.
        • Koster T.
        • Briet E.
        • et al.
        Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation.
        Lancet. 1994; 344: 1453-1457
        • Voorberg J.
        • Roelse J.
        • Koopman R.
        • et al.
        Association of idiopathic venous thromboembolism with single point mutation at Arg506 of factor V.
        Lancet. 1994; 343: 1535-1536
        • Weinmann E.E.
        • Salzman E.W.
        Deep-vein thrombosis.
        N Engl J Med. 1994; 331: 1630-1641
        • Zoller B.
        • Bemtsdotter A.
        • de Frutos P.G.
        • et al.
        Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S.
        Blood. 1995; 85: 3518-3523
        • Zoller B.
        • Dahlbäck B.
        Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis.
        Lancet. 1994; 343: 1536-1538
        • Zoller B.
        • Svensson P.J.
        • He X.
        • et al.
        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: 2521-2524

      Article info

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      DOI: https://doi.org/10.1016/S0272-2712(18)30293-2

      Copyright

      © 1996 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

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