Thrombophilie

Zusammenfassung

Es wird ein Überblick über Definitionen, Epidemiologie, Klinik der angeborenen, sowie klinisch relevanter erworbener Thrombophilien gegeben. Diagnostische und therapeutische Strategien werden aufgezeigt.

Summary

A survey on definitions, epidemiology, clinical manifestations of congenital thrombophilias and clinical relevant acquired thrombophilias is given. Diagnostic and therapeutical strategies are presented.

Schlüsselwörter

Thrombophilie - venöse Thrombose - Antithrombinmangel - Protein-C-Mangel - Protein-S-Mangel - Faktor-V-Leiden - Prothrombinvariation - Lupusantikoagulans

Keywords

Thrombophilia - venous thrombosis - antithrombin deficiency - protein C deficiency - protein S deficiency - factor V Leiden - prothrombin variation - lupus anticoagulant

• Literatur

• 1 Bertina RM, Koeleman BPC, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64.
• 2 Branson HE, Katz J, Marble R. et al. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2: 1165.
• 3 Chowdury V, Lane DA, Mille B. et al. Homozygous antithrombin deficiency: report of two new cases (99Leu to Phe) associated with arterial and venous thrombosis. Thromb Haemost 1994; 72: 198.
• 4 Crowther MA, Ginsberg JS, Julian J. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003; 349: 1133-8.
• 5 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.
• 6 D’Angelo A, della Valle P, Crippa L. et al. Autoimmune protein S deficiency in a boy with severe thromboembolic disease. N Engl J Med 1993; 328: 1753-7.
• 7 De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 1996; 87: 3531-44.
• 8 De Stefano V, Leone G, Matrangelo 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. Sem Thromb Haemost 1994; 72: 352.
• 9 Den Heijer M, Koster T, Blom HJ. et al. Hyperhomocysteinemia as a risk factor for deep vein thrombosis. N Engl J Med 1996; 334: 759.
• 10 Dreyfus M, Magny FJ, Bridey F. et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 1991; 325: 1565.
• 11 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516.
• 12 Eichinger S, Pabinger I, Stümpflen A. et al. The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost 1997; 77: 624.
• 13 Eichinger S, Stümpflen A, Hirschl M. et al. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost 1998; 80: 566.
• 14 Eichinger S, Schönauer V, Weltermann A. et al. Thrombin activatable fibrinolysis inhibitor (TAFI) and the risk of recurrent venous thrombosis. Blood 2004; 103: 3773-6.
• 15 Ehrenforth S, Nemes L, Mannhalter C. et al. Impact of environmental and hereditary risk factors on the manifestation of thrombophilia in homozygous carriers of factor V:G1691A. J Thromb Haemost 2004; 2: 430-6.
• 16 Falcon CR, Cattaneo M, Panzeri D. et al. High prevalence of hyperhomocyst(e)inemia in patients with juvenile venous thrombosis. Arterioscler Thromb 1994; 14: 1080.
• 17 Frosst P, Blom HJ, Milos R. et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics 1995; 10: 111-3.
• 18 Griffin J, Evatt B, Zimmerman T. et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370.
• 19 Heijboer H, Brandjes DPM, Buller HR. et al. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis. N Engl J Med 1990; 323: 1512.
• 20 Khamashta MA, Cuadrado MJ, Mujic F. et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993-7.
• 21 Koeleman BPC, Reitsma PH, Allaart CF. et al. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient patients. Blood 1994; 84: 1031.
• 22 Koster T, Rosendaal FR, de Ronde H. et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503.
• 23 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152.
• 24 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thrombosis. N Engl J Med 2000; 343: 457-62.
• 25 Lane DA, Olds RJ, Boisclair M. et al. Antithrombin III mutation database: First update. Thromb Haemost 1993; 70: 361.
• 26 Lechner K, Kyrle PA. Antithrombin III concentrates – are they clinically useful?. Thromb Haemost 1995; 73: 340-8.
• 27 Lechner K, Pabinger-Fasching I. Lupus anticoagulants and thrombosis. A study of 25 cases and review of the literature. Haemostasis 1985; 15: 254-62.
• 28 Male C, Lechner K, Eichinger S. et al. Clinical significance of lupus anticoagulants in children. J Pediatr 1999; 134: 199.
• 29 Marlar RA, Montgomery RR, Madden RM. Homozygous protein C deficiency. In: Bertina RM. (ed). Protein C and related proteins. Edinburgh, UK: Churchill Livingstone; 1988: 182.
• 30 Miletich J, Sherman L, Broze Jr. G. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987; 17: 991.
• 31 Mustafa S, Pabinger I, Mannhalter C. Protein S deficiency type I: identification of point mutations in 9 of 10 families. Blood 1995; 86: 3444.
• 32 Pabinger I, Brucker S, Kyrle PA. et al. Hereditary deficiency of antithrombin III, protein C and protein S: Prevalence in patients with a history of venous thrombosis and criteria for rational patient screening. Blood Coagul Fibrinolysis 1992; 3: 547.
• 33 Pabinger I, Kyrle PA, Heistinger M. et al. The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: A prospective cohort study. Thromb Haemost 1994; 71: 441.
• 34 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.
• 35 Pabinger I, Schneider B. the GTH Study Group on Natural Inhibitors. The thrombotic risk in hereditary antithrombin III-, protein C- and protein S-deficiency: a cooperative retrospective study. Arterioscler Thromb Vasc Biol 1996; 16: 742-8.
• 36 Palareti G, Legnani C, Cosmi B. et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost 2002; 87: 7-12.
• 37 Poort SR, Rosendaal FR, Reitsma PH. et al. A common genetic variation in the 3’ untranslated region of the prothrombin gene is associated with elevated plasma thrombin levels and an increase in venous thrombosis. Blood 1996; 10: 3698-703.
• 38 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133.
• 39 Reitsma PH, Bernardi F, Doig RG. et al. Protein C deficiency:A database of mutations, 1995 update. Thromb Haemost 1995; 73: 876.
• 40 Ridker PM, Miletich JP, Stampfer MJ. et al. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 1995; 92: 2800-2.
• 41 Rintelen C, Pabinger I, Knöbl P. et al. Probability of recurrence of thrombosis in patients with and without factor V Leiden. Thromb Haemost 1996; 75: 229-32.
• 42 Rosendaal FR, Koster T, Vandenbroucke JP. et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504.
• 43 Schafer AI. Bleeding and thrombosis in the myeloproliferative disorders. Blood 1984; 64: 1-12.
• 44 Schwarz HP, Fischer M, Hopmeier P. et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297.
• 45 Lindmarker P, Schulman S, Sten-Linder M. et al. The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation. Thromb Haemost 1999; 81: 684.
• 46 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330 (05) 17.
• 47 Tait R, Walker ID, Perry DJ. et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87: 106.
• 48 Tait RC, Walker ID, Reitsma PH. et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87.
• 49 Thaler E, Balzar E, Kopsa H. et al. Acquired antithrombin III deficiency in patients with glomerular proteinuria. Haemostasis 1978; 7: 257-72.
• 50 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10: 369-90.
• 51 Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res 1995; 78: 1-31.
• 52 Vandenbroucke JP, 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.
• 53 Zöller B, Bernsdotter A, Garcia de Frutos P. et al. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518.