12
Views
4
CrossRef citations to date
0
Altmetric
Original Article

Familial thrombophilia: Clinical and molecular analysis of Swedish families with inherited resistance to activated protein C or protein S deficiency

Pages 19-46 | Published online: 17 Mar 2010

References

  • Furie B, Furie B C. The molecular basis of blood coagulation. Cell 1988; 53: 505–18
  • Davie EW. Biochemical and molecular aspects of the coagulation cascade. Thromb Haemost 1995; 74: 1–6
  • Hirsh J, Hull R D, Raskob G E. Epidemiology and pathogenesis of venous thrombosis. J Am Coll Cardiol 1986; 8: 104B–13B
  • Collen D, Lijnen H R. Molecular basis of fibrinolysis, as relevant for thrombolytic therapy. Thromb Haemost 1995; 74: 167–71
  • Lane D A, Olds R J, Thein S L. Antithrombin and its deficiency. Haemostasis and Thrombosis 3rd ed., A L Bloom, C D Forbes, D P Thomas, E GD Tuddenhamn. Churchill Livingstone, Edinburgh 1994; 655–70
  • Broze G J, Tollefsen D M. Regulation of blood coagulation by protease inhibitors. The molecular basis of blood diseases, G Stamatoyannopoulos, A W Nienhuis, P W Majerus, H Varmus. W.B. Saunders, Philadelphia 1994; 629–56
  • Dahlbäck B, Stenflo J. The protein C anticoagulant system. The molecular basis of blood diseases, G Stamatoyannopoulos, A W Nienhuis, P W Majerus, H Varmus. W.B. Saunders, Philadelphia 1994; 599–628
  • Goldhaber SZ. Epidemiology of pulmonary embolism and deep vein thrombosis. Haemostasis and Thrombosis, 3rd ed., A L Bloom, C D Forbes, D P Thomas, E GD Tuddenham. Churchill Livingstone, Edinburgh 1994; 1327–33
  • Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thrombosis et Diathesis Haemorrhagica 1965; 13: 516–30
  • Griffin J H, Evatt B L, Zimmerman T S, Kleiss A J, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370–3
  • Comp P C, Esmon C T. Recurrent thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525–8
  • Heijboer H, Brandjes D, Büller H R, Sturk A, ten Cate J W. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. N Engl J Med 1990; 23: 1512–6
  • Malm J, Laurell M, Nilsson I M, Dahlbäck B. Thromboembolic disease - critical evaluation of laboratory investigation. Thromb Haemost 1992; 68: 7–13
  • 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: 1004–8
  • Griffin J H, Evatt B L, Wideman C, Fernandez J A. Anticoagulant protein C pathway defective in a majority of thrombophilic patients. Blood 1993; 82: 1989–93
  • Koster T, Rosendaal F R, de Ronde F, Briët E, Vandenbroucke J P, Bertina R M. Venous thrombosis due to poor response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503–6
  • Faioni E M, Franchi F, Asti D, Sacchi E, Bernardi F, Mannucci P M. Resistance to activated protein C in nine thrombophilic families: Interference in a protein S functional assay. Thromb Haemost 1993; 70: 1067–71
  • Halbmayer W M, Haushofer A, Schön R, Fischer M. 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 1994; 5: 51–7
  • Svensson P J, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517–21
  • Zöller B, Holm J, Dahlbäck B. Resistance to activated protein C due to a factor V gene mutation. The most common inherited risk factor of thrombosis. Trends Cardiovasc Med 1996; 6: 45–53
  • 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
  • Zöller B, Svensson P J, 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
  • Zöller B, He X, Dahlbäck B. Homozygous APC resistance combined with protein S deficiency in a young boy with severe thrombotic disease. Thromb Haemost 1995; 73: 743–5
  • 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
  • Zöller B, Holm J, Svensson P J, Dahlbäck B. Elevated levels of prothrombin activation fragment 1+2 in plasma from patients with inherited APC resistance and/or protein S deficiency. Thromb Haemost 1996; 75: 270–4
  • Zöller 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
  • Esmon C T, Schwarz H P. An update on clinical and basic aspects of the protein C anticoagulant pathway. Trends Cardiovasc Med 1995; 5: 141–8
  • Fay P J, Smudzin T M, Walker F J. Activated protein C-catalyzed inactivation of factor VIII and VIIIa. J Biol Chem 1991; 260: 20139–45
  • Kalafatis M, Bertina R M, Rand M D, Mann K G. Characterization of the molecular defect in factor VR506Q. J Biol Chem 1995; 270: 4053–7
  • Kalafatis M, Rand M D, Mann K G. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J Biol Chem 1994; 269: 31869–80
  • Walker FJ. Protein S and the regulation of activated protein C. Semin Thromb Hemost 1984; 10: 131–8
  • 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
  • Váradi K, Rosing J, Tans G, Schwarz H P. Influence of factor V and factor Va on APC-induced cleavage of human factor VIII. Thromb Haemost 1995; 73: 730–1
  • Seligsohn U, Berger A, Abend A, et al. Homozygous protein C deficiency manifested by massive thrombosis in the newborn. N Engl J Med 1984; 310: 559–62
  • Marlar R A, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost 1990; 16: 299–309
  • 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; 81: 1396–400
  • Shen N LL, Fan S T, Pyati J, Graff R, Lapolla R J, Edgington T S. The serine protease cofactor factor V is synthesized by lymphocytes. J Immunol 1993; 150: 2992–3001
  • Bertina R M, Koeleman B PC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64–7
  • Greengard J S, Sun X, Xu X, Fernandez J A, Griffin J H, Evatt B L. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994; 343: 1362–3
  • Voorberg J, Roelse J, Koopman R, et al. Association of idiopathic thromboembolism with single point mutation at Arg506 of factor V. Lancet 1994; 343: 1535–6
  • Sun X, Evatt B L, Griffin J H. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120–5
  • Heeb M J, Kojima Y, Greengard J S, Griffin J H. Activated protein C resistance: Molecular mechanisms based on studies using purified Gln506-factor V. Blood 1995; 85: 3405–11
  • Nicolaes G AF, Tans G, Thomassen M CLGD, 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: 21158–66
  • Rosing J, Hoekema L, Nicolaes G AF, et al. Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor Var506q by activated protein C. J Biol Chem 1995; 270: 27852–8
  • Aparicio C, Dahlbäck B. Molecular mechanisms of activated protein C resistance based on studies using purified FV:Q506. Biochem J 1996; 313: 467–72
  • Liu X Y, Nelson D, Grant C, Morthland V, Goodnight S H, Press R D. Molecular detection of a common mutation in coagulation factor V causing thrombosis via hereditary resistance to activated protein C. Diagnostic Molecular Pathology 1995; 4: 191–7
  • Jorquera J I, Montoro J M, Fernández M A, Aznar J A, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344: 1162–3
  • Trossaërt M, Conard J, Horellou M H, et al. Modified APC resistance assay for patients on oral anticoagulants. Lancet 1994; 344: 1709
  • Dahlbäck B, Hillarp A, Rosen S, Zöller B. Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis. Ann Hematol 1996; 72: 166–76
  • Koeleman B PC, Reitsma P H, Allaart R C, Bertina R M. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031–5
  • Koeleman B PC, van Rumpf D, Hamulyák K, Reitsma P H, Bertina R M. Factor V Leiden. An additional risk factor for thrombosis in protein S deficient families?. Thromb Haemost 1995; 74: 580–3
  • Bertina R M, Reitsma P H, Rosendaal F R, Vandenbroucke J P. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 1995; 74: 449–53
  • De Lucia D, De Blasio G, Belli A, et al. High prevalence of activated protein C resistance in patients with systemic sclerosis. Int J Clin Lab Res 1996; 25: 226–7
  • Ouriel K, Green R M, Deweese J A, Cimino C. Activated protein C resistance: prevalence and implications in peripheral vascular disease. J Vasc Surg 1996; 23: 46–52
  • Hillarp A, Dahlbäck B, Zöller B. Activated protein C resistance: from phenotype to genotype and clinical practice. Blood Rev 1995; 9: 201–12
  • Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10: 369–90
  • Broekmans A W, Conard J. Hereditary protein C deficiency. Protein C and related proteins, R M Bertina. Churchill Livingstone, Edinburgh 1988; 160–81
  • Engesser L, Broekmans A W, Briët E, Brommer E JP, Bertina R M. Hereditary protein S deficiency: Clinical manifestations. Ann Intern Med 1987; 106: 677–82
  • Emmerich J, Poirier O, Evans A, et al. Myocardial infarction, Arg506 to Gln factor V mutation, and activated protein C resistance. Lancet 1995; 345: 321
  • van Bockxmeer F M, Baker R I, Taylor R R. Premature ischaemic heart disease and the gene for coagulation factor V. Nature Medicine 1995; 1: 185
  • Ridker P M, Hennekens C H, Lindpaintner K, Stampfer M J, Eisenberg P R, Miletich J P. 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
  • Cushman M, Bhushan F, Bovill E, Tracy R. Plasma resistance to activated protein C in venous and arterial thrombosis. Thromb Haemost 1994; 72: 647
  • Samani N, Lodwick D, Martin D, Kimber P. Resistance to activated protein C and risk of premature myocardial infarction. Lancet 1994; 344: 1709–10
  • Forsyth P D, Dolan G. Activated protein C resistance in cases of cerebral infarction. Lancet 1995; 345: 795
  • Catto A, Carter A, Ireland H, et al. Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke. Arterioscler Thromb Vasc Biol 1995; 15: 783–5
  • Kontula K, Ylikorkala A, Miettinen H, et al. Arg506Gln factor V mutation (factor V Leiden) in patients with ischaemic cerebrovascular disease and survivors of myocardial infarction. Thromb Haemost 1995; 73: 558–60
  • Eritsland J, Gjonnes G, Sandset P M, Seljeflot I, Arnesen H. Activated protein C resistance and graft occlusion after coronary artery bypass surgery. Thromb Res 1995; 79: 223–6
  • Press R D, Liu X Y, Beamer N, Coull B M. Ischemic stroke in the elderly. Role of the common factor V mutation causing resistance to activated protein C. Stroke 1996; 27: 44–8
  • Biasiutti F D, Merlo C, Furlan M, Sulzer I, Binder B R, Lämmle B. No association of APC resistance with myocardial infarction. Blood Coagul Fibrinolysis 1995; 6: 456–9
  • Holm J, Zöller B, Berntorp E, Erhardt L, Dahlbäck B. Prevalence of factor V gene mutation among myocardial infarction patients and healthy controls higher in Sweden than in other countries. J Intern Med 1996; 239: 221–6
  • März W, Seydewitz H, Winkelmann B, Chen M, Nauck M. Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease. Lancet 1995; 345: 526–7
  • Nowak-Göttl U, Koch H G, Aschka I, et al. Resistance to activated protein C (APCR) in children with venous or arterial thrombosis. Br J Haematol 1996; 92: 992–8
  • Lindblad B, Svensson P J, Dahlbäck B. Arterial and venous thromboembolism with fatal outcome in a young man with inherited resistance to activated protein C. Lancet 1994; 343: 917
  • Holm J, Zöller B, Svensson P J, Berntorp E, Erhardt L, Dahlbäck B. Myocardial infarction associated with homozygous resistance to activated protein C. Lancet 1994; 344: 952–3
  • Simioni P, de Rode H, Prandoni P, Saladini M, Bertina R M, Girolami A. Ischemic stroke in young patients with activated protein C resistance. A report of three cases belonging to three different kindreds. Stroke 1995; 26: 885–90
  • Vandenbroucke J P, Koster T, Briët E, Reitsma P H, Bertina R M, Rosendaal F R. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453–7
  • Hellgren M, Svensson P J, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 173: 210–3
  • Bokarewa M I, Bremme K, Blombäck M. Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473–8
  • Comp P C, Nixon R R, Cooper M R, Esmon C T. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082–8
  • Schwarz H P, Fischer M, Hopmeier P, Batard M A, Griffin J H. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297–300
  • Sas G, Blaskó G, Petrö I, Griffin J H. A protein S deficient family with portal vein thrombosis. Thromb Haemost 1985; 54: 724
  • Bertina RM. Hereditary protein S deficiency. Haemostasis 1985; 15: 241–6
  • Comp P C, Doray D, Patton D, Esmon C T. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504–8
  • Kamiya T, Sugihara T, Ogata K, et al. Inherited deficiency of protein S in a Japanese family with recurrent venous thrombosis; a study of three generations. Blood 1986; 67: 406–10
  • Mannucci P M, Tripodi A, Bertina R M. Protein S deficiency associated with “juvenile” arterial and venous thrombosis. Thromb Haemost 1986; 55: 440
  • Pabinger I, Bertina R M, Lechner K, Niessner H, Korninger C, Deutsch E. Protein S deficiency in 7 Austrian families. Thromb Res Suppl 1986; 6: 136
  • Marchetti G, Legnani C, Ferrati M, et al. Study of a protein S gene polymorphism at DNA and mRNA level in a family with symptomatic protein S deficiency. Br J Haematol 1993; 85: 173–5
  • Broekmans A W, Van Der Linden I K, Jansen-Koeter Y, Bertina R M. Prevalence of protein C (PC) and protein S (PS) deficiency in patients with thromboembolic disease. Thromb Res 1986; 135a, Suppl 6
  • Gladson C L, Scharrer I, Hach V, Beck K H, Griffin J H. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost 1988; 59: 18–22
  • Ben-Tal O, Zivelin A, Seligsohn U. The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. Thromb Haemost 1989; 61: 50–4
  • Tabernero M D, Tomas J F, Alberca I, Orfao A, Borrasca A L, Vicente V. Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis. Am J Hematol 1991; 36: 249–54
  • Koster T, Rosendaal F R, Briet E, et al. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden thrombophilia study). Blood 1995; 85: 2756–61
  • Dahlbäck B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci USA 1981; 78: 2512–6
  • Dahlbäck B. Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. Biochem J 1983; 209: 847–56
  • Dahlbäck B. Inhibition of protein Ca cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem 1986; 261: 12022–7
  • Briet E, Broekmans A W, Engesser L. Hereditary protein S deficiency. Protein C and related proteins, R M Bertina. Churchill Livingstone, Edinburgh 1988; 203–12
  • Mannucci P M, Valsecchi C, Krashmalnicoff A, Faioni E M, Tripodi A. Familial dysfunction of protein S. Thromb Haemost 1989; 62: 763–6
  • Maccaferri M, Legnani C, Preda L, Palareti G. Protein S activity in patients with heredofamilial protein S deficiency and in patients with juvenile venous thrombosis. Results of a functional method. Thromb Res 1991; 64: 647–58
  • Faioni E M, Boyer-Neumann C, Wolf M, Meyer D, Mannucci P M. Another protein S functional assay is sensitive to resistance to activated protein C. Thromb Haemost 1994; 72: 648
  • Cooper P C, Hampton K K, Makris M, Abuzenadah A, Paul B, Preston F E. Further evidence that activated protein C resistance can be misdiagnosed as inherited functional protein S deficiency. Br J Haematol 1994; 88: 201–3
  • Iijima K, Inoue N, Nakamura K, et al. Inherited deficiency of functional and free form protein S. Acta Haematol Japon 1989; 52: 126–33
  • Lauer C G, Reid T J, Wideman C S, Evatt B L, Alving B M. Free protein S deficiency in a family with venous thrombosis. J Vasc Surg 1990; 12: 541–4
  • Härdig Y, Rezaie A R, Dahlbäck B. High affinity binding of human vitamin K-dependent protein S to a truncuted recombinant β-chain of C4b-binding protein expressed in Escherichia coli. J Biol Chem 1993; 268: 3033–6
  • Hillarp A, Dahlbäck B. Novel subunit in C4b-binding protein required for protein S binding. J Biol Chem 1988; 263: 12759–64
  • Hillarp A, Hessing M, Dahlbäck B. Protein S binding in relation to the subunit composition of human C4b-binding protein. FEBS Lett 1989; 259: 53–6
  • Griffin J H, Gruber A, Fernández J A. Reevaluation of total, free and bound protein S and C4b-binding protein levels in plasma anticoagulated with citrate or hirudin. Blood 1992; 79: 3203–11
  • Garcia de Frutos P, Alim R IM, Härdig Y, Zöller B, Dahlbäck B. Differential regulation of α- and β-chains of C4b-binding protein during acute-phase response resulting in stable plasma levels of free anticoagulant protein S. Blood 1994; 84: 815–22
  • 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
  • Gouault-Heilmann M, Leroy-Matheron C, Levent M. Inherited protein S deficiency: Clinical manifestations and laboratory findings in 63 patients. Thromb Res 1994; 76: 269–79
  • Reitsma P H, Ploos van Amstel H K, Bertina R M. Three novel mutations in five unrelated subjects with hereditary protein S deficiency type I. J Clin Invest 1994; 93: 486–92
  • Gandrille S, Borgel D, Eschwege-Gufflet V, et al. Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using scanning method for analysis of the protein S active gene. Blood 1995; 85: 130–8
  • Gómez E, Poort S R, Bertina R M, Reitsma P H. Identification of eight point mutations in protein S deficiency type I - analysis of 15 pedigrees. Thromb Haemost 1995; 73: 750–5
  • Ploos van Amstel H K, Reitsma P H, Hamulyak K, de Die-Smulders C EM, Mannucci P M, Bertina R M. A mutation in the protein S pseudogene is linked to protein S deficiency in a thrombophilic family. Thromb Haemost 1989; 62: 897–901
  • Ploos van Amstel H K, Huisman M V, Reitsma P H, ten Cate J W, Bertina R M. Partial protein S gene deletion in a family with hereditary thrombophilia. Blood 1989; 73: 479–83
  • Schmidel D K, Nelson R M, Broxson E H, Comp P C, Marlar R A, Long G L. A 5.3-kb deletion including exon XIII of the protein S gene occurs in two protein S-deficient families. Blood 1991; 77: 551–9
  • Borgel D, Gandrille S, Gouault-Heilmann M, Aiach M. First frameshift mutation in the active protein S gene associated with a quantitative hereditary deficiency. Blood Coagul Fibrinolysis 1994; 5: 593–600
  • Gómez E, Ledford M R, Pegelow C H, Reitsma P H, Bertina R M. Homozygous protein S deficiency due to a one base pair deletion that leads to a stop codon in exon III of the protein S gene. Thromb Haemost 1995; 71: 723–6
  • Duchemin J, Gandrille S, Borgel D, et al. The Ser 460 to Pro substitution of the protein S a (PROS1) gene is a frequent mutation associated with free protein S (type IIa) deficiency. Blood 1995; 86: 3436–43
  • Formstone C J, Wacey A I, Berg L-P, et al. Detection and characterization of seven novel protein S (PROS) gene lesions: Evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy. Blood 1995; 86: 2632–41
  • Yamazaki T, Hamaguchi M, Katsumi A, et al. A quantitative protein S deficiency associated with a novel nonsense mutation and markedly reduced levels of mutated mRNA. Thromb Haemost 1995; 74: 590–5
  • Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K. Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood 1994; 83: 683–90
  • Girolami A, Simioni P, Lazzaro A R, Cordiano I. Severe arterial cerebral thrombosis in a patient with protein S deficiency (moderately reduced total and markedly reduced free protein S): a family study. Thromb Haemost 1989; 61: 144–7
  • Sie P, Boneu B, Biermé R, Wiesel M L, Grunebaum L, Cazenave J P. Arterial thrombosis and protein S deficiency. Thromb Haemost 1989; 62: 1040
  • Allaart R C, Aronson D C, Ruys T, et al. Hereditary protein S deficiency in young adults with arterial occlusive disease. Thromb Haemost 1990; 64: 206–10
  • Scott B D, Esmon C T, Comp P C. The natural anticoagulant protein S is decreased in male smokers. Am Heart J 1991; 122: 76–80
  • Heeb M J, Mesters R M, Tans G, Rosing J, Griffin J H. Binding of protein S to factor Va associated with inhibition of prothrombinase that is independent of activated protein C. J Biol Chem 1993; 268: 2872–7
  • Heeb M J, Rosing J, Bakker H M, Fernandez J A, Tans G, Griffin J H. Protein S binds to and inhibits factor Xa. Proc Natl Acad Sci USA 1994; 91: 2728–32
  • van't Veer C, Hackeng T M, Biesbroeck D, Sixma J J, Bouma B N. Increased prothrombin activation in protein S-deficient plasma under flow conditions on endothelial cell matrix: an independent anticoagulant function of protein S in plasma. Blood 1995; 85: 1815–21
  • Koppelman S J, Hackeng T M, Sixma J J, Bouma B N. Inhibition of the intrinsic factor X activating complex by protein S: Evidence for a specific binding of protein S to factor VIII. Blood 1995; 86: 1062–71
  • Gasic G P, Arenas C P, Gasic T B, Gasic G J. Coagulation factors X, Xa, and protein S as potent mitogens of cultured aortic smooth muscle cells. Proc Natl Acad Sci USA 1992; 89: 2317–20
  • Stitt T N, Conn G, Gore M, et al. The anti-coagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family receptor tyrosine kinases. Cell 1995; 80: 661–70
  • Schafer AI. The hypercoagulable states. Ann Intern Med 1985; 102: 814–28
  • Sipes S L, Weiner C P. Venous thromboembolic disease in pregnancy. Seminars in Perinatology 1990; 14: 103–8
  • De Stefano V, Leone G, Mastrangelo S, et al. 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 1994; 72: 352–8
  • Pabinger I, Kyrle P A, Heistinger M, Eichinger S, Wittman E, Lechner K. The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: a prospective study. Thromb Haemost 1994; 71: 441–5
  • Pabinger I, Schneider B, the GTH study group on natural inhibitors. Thrombotic risk of women with hereditary antithrombin III-, protein C- and protein S-deficiency taking oral contraceptive medication. Thromb Haemost 1994; 71: 548–52
  • Bauer KA. Management of patients with hereditary defects predisposing to thrombosis including pregnant women. Thromb Haemost 1995; 74: 94–100
  • Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: First analyses of the Canadian registry of VTE. Blood 1994; 83: 1251–7
  • Gandrille S, Greengard J S, Alhenc-Gelas M, et al. 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 1995; 86: 219–24
  • Hallam P J, Millar D S, Krawczak M, Kakkar V V, Cooper D N. Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency. J Med Genet 1995; 32: 543–5
  • van Boven H H, Reitsma P H, Rosendaal F R, et al. Factor V Leiden (FVR:506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75: 417–21
  • Mannucci P M, Tripodi A, Bottasso B, et al. Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes. Thromb Haemost 1992; 67: 200–2
  • Bauer KA. New markers for in vivo coagulation. Curr Opin Hematol 1994; 1: 341–6
  • Holm J, Berntorp E, Carlsson R, Erhardt L. Low-dose warfarin decreases coagulability without affecting prothrombin complex activity. J Intern Med 1993; 234: 303–8
  • Szczeklik A, Krzanowski M, Góra P, Radwan J. Antiplatelet drugs and generation of thrombin in clotting blood. Blood 1992; 80: 2006–11
  • Yaso T, Oshima S, Imanishi M, et al. Effects of aspirin DL-lysine on thrombin generation in unstable angina pectoris. Am J Cardiol 1993; 71: 1164–8
  • Nordström M, Lindblad B, Bergqvist D, Kjellström T. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med 1992; 232: 155–60
  • Zöller B, Dahlbäck B. Resistance to activated protein C caused by a factor V gene mutation. Curr Opin Hematol 1995; 2: 358–64
  • Rees D C, Cox M, Clegg J B. World distribution of factor V Leiden. Lancet 1995; 346: 1133–4
  • Rees D C, Cox M, Martinsson J J, Clegg J B. Evidence for a single origin of factor V Leiden. Br J Haematol 1996; 92: 1022–5

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.