50 Jahre GTH – Erwartungen, Erfolge, Enttäuschungen

Zusammenfassung

Die Deutsche Arbeitsgemeinschaft für Blutgerinnungsforschung (DAB) wurde 1956 gegründet und 1982 in die Gesellschaft für Thrombose und Hämostase (GTH), eine multinationale, vorwiegend deutschsprachige Gesellschaft umgewandelt. In den letzten vier Dekaden (seit meiner Tätigkeit auf diesem Gebiet) war der Fortschritt der Grundlagenforschung enorm, der Fortschritt in Diagnostik und Therapie auf den verschiedenen Teilgebieten der Hämostaseologie unterschiedlich. Die größten Fortschritte waren die Herstellung effektiver und infektionssicherer Faktor-VIII- und -IXKonzentrate, die Entdeckung thrombophiler Diathesen, die Einführung nicht invasiver bildgebender Verfahren zur Diagnostik venöser Thromboembolien und die Diagnostik und Therapie immunologisch bedingter Koagulopathien. Die vergangenen Jahrzehnte waren auch geprägt durch Versuche, die Diagnostik und Therapie, insbesondere bei thromboembolischen Erkrankungen zu optimieren und standardisieren (evidence-based medicine). Trotzdem sind Diagnostik und Therapie individuell in vielen Fällen immer noch schwierig, was die Beratung durch einen auf diesem Gebiet spezialisierten Fachmann (Hämostaseologen) erforderlich macht.

Summary

The Deutsche Arbeitsgemeinschaft für Blutgerinnungsforschung (DAB) (German Working Party on Blood Coagulation) was founded in 1956 by a few German specialists in haemostasis. In 1982, the DAB was replaced by the Society on Thrombosis and Haemostasis (GTH), which was multinational, with emphasis on German speaking countries. Since I started in this field there was steady progress in the diagnosis and treatment of haemorrhagic and thrombotic disorders. Milestones were the production of effective and safe factor VIII and IX concentrates for haemophilia treatment, the diagnosis of venous thromboembolic disorders by non-invasive methods, the definition of thrombophilic states by laboratory methods and the diagnosis and treatment of immune coagulopathies. In other fields, progress was less impressive.

During the last decades attempts have been made to optimize and standardize diagnosis and treatment in the thrombosis and haemostasis field (evidence based medicine). Despite guidelines and consensus statements the clinical problems in individual patients are still frequent and considerable. Therefore, physicians with a special expertise in the field of thrombosis and haemostasis are needed.

Schlüsselwörter

Hämophilie - venöse Thromboembolie - Thrombozyten

Keywords

Haemophilia - venous thromboembolism - platelet disorders

• References

• 1 Antithrombotic Trialists’ Collaboration.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324 7329 71-86.
• 2 Archimbaud E, Ottmann OG, Yin JA. et al. A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEGrHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia. Blood 1999; 94: 3694-701.
• 3 Berntorp E. Second generation, B-domain deleted recombinant factor VIII. Thromb Haemost 1997; 78: 256-60.
• 4 Berntorp E, Astermark J, Bjorkman S. et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia 2003; 9 (Suppl. 01) 1-4.
• 5 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369 6475 64-7.
• 6 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-9.
• 7 Bounameaux Y. Determination of factor VIII with a one-stage method. Acta Haematol 1957; 17: 355-9.
• 8 Brackmann HH, Oldenburg J, Schwaab R. Immune tolerance for the treatment of factor VIII inhibitors – twenty years ‘bonn protocol‘. Vox Sang 1996; 70 (Suppl. 01) 30-5.
• 9 Brinker A, He R, Desai M. et al. Safety of ximelagatran. JAMA 2005; 293: 2859.
• 10 Buller HR, Agnelli G, Hull RD. et al. Antithrombotic therapy for venous thromboembolic disease: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126 (Suppl. 03) 401S-28.
• 11 Buller HR, Davidson BL, Decousus H. et al. Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349: 1695-702.
• 12 Dahl OE, Andreassen G, Aspelin T. et al. Prolonged thromboprophylaxis following hip replacement surgery--results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin(Fragmin). Thromb Haemost 1997; 77: 26-31.
• 13 Di Nisio M, Middeldorp S, Buller HR. Direct thrombin inhibitors. N Engl J Med 2005; 353: 1028-40.
• 14 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-30.
• 15 Eichinger S, Minar E, Bialonczyk C. et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA 2003; 290: 1071-4.
• 16 Fanikos J, Stapinski C, Koo S. et al. Medication errors associated with anticoagulant therapy in the hospital. Am J Cardiol 2004; 94: 532-5.
• 17 Fraser DG, Moody AR, Morgan PS. et al. Diagnosis of lower-limb deep venous thrombosis: a prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002; 136: 89-98.
• 18 Furlan M, Robles R, Galbusera M. et al. Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578-84.
• 19 Gould MK, Dembitzer AD, Doyle RL. et al. Lowmolecular- weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999; 130: 800-9.
• 20 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemost 1981; 45: 200-3.
• 21 Griffin JH, Evatt B, Zimmerman TS. et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-3.
• 22 Gurwitz JH, Field TS, Harrold LR. et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003; 289 (Suppl. 09) 1107-16.
• 23 Kemkes-Matthes B, Nees M, Kuhnel G. et al. Protein Z influences the prothrombotic phenotype in factor V Leiden patients. Thromb Res 2002; 106: 183-5.
• 24 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.
• 25 Knoebl P, Derfler K, Korninger L. et al. Elimination of acquired factor VIII antibodies by extracorporal antibody-based immunoadsorption (Ig-Therasorb). Thromb Haemost 1995; 74: 1035-8.
• 26 Konstantinides S. Should thrombolytic therapy be used in patients with pulmonary embolism?. Am J Cardiovasc Drugs 2004; 4: 69-74.
• 27 Krebs H, Domsch C, Adelhard K. et al. The national GTH haemophilia registry as database within the scope of the German human genome project. Hämostaseologie 2003; 23: 18-23.
• 28 Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet 2005; 365 9465 1163-74.
• 29 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-62.
• 30 Li J, Yang C, Xia Y. et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001; 98: 3241-8.
• 31 Ljung RC. Prenatal diagnosis of haemophilia. Baillieres Clin Haematol 1996; 9: 243-57.
• 32 Mannucci PM, Ruggeri ZM, Pareti FI. et al. 1-Deamino- 8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet 1977; 1 8017 869-72.
• 33 Mannucci PM, Schimpf K, Brettler DB. et al. Low risk for hepatitis C in hemophiliacs given a highpurity, pasteurized factor VIII concentrate. International Study Group. Ann Intern Med 1990; 113: 27-32.
• 34 American College of Chest Physicians.. Opinions regarding the diagnosis and management of venous thromboembolic disease. ACCP Consensus Committee on Pulmonary Embolism. Chest 1998; 113: 499-504.
• 35 No authors listed.. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet 1975; 2 7924 45-51.
• 36 The Columbus Investigators.. Low-molecularweight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657-62.
• 37 Nurmohamed MT, Rosendaal FR, Buller HR. et al. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta- analysis. Lancet 1992; 340 8812 152-6.
• 38 Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft für Thrombose- und Hämostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol 1996; 16: 742-8.
• 39 Perrier A, Desmarais S, Miron MJ. et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353 9148 190-5.
• 40 Perrier A, Roy PM, Sanchez O. et al. Multidetector- row computed tomography in suspected pulmonary embolism. N Engl J Med 2005; 352: 1760-8.
• 41 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 prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
• 42 Proctor RR, Rapaport SI. The partial thromboplastin time with kaolin. A simple screening test for firststage plasma clotting factor deficiencies. Am J Clin Pathol 1961; 36: 212-9.
• 43 Quinlan DJ, McQuillan A, Eikelboom JW. Lowmolecular- weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med 2004; 140: 175-83.
• 44 Rabiner SF, Telfer MC. Home transfusion for patients with hemophilia A. N Engl J Med 1970; 283: 1011-5.
• 45 Rieger M, Mannucci PM, Kremer Hovinga JA. et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005; 106: 1262-7.
• 46 Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101: 2089-93.
• 47 Sasahara AA, Cannilla JE, Belko JS. et al. Urokinase therapy in clinical pulmonary embolism. A new thrombolytic agent. N Engl J Med 1967; 277: 1168-73.
• 48 Schimpf K, Brackmann HH, Kreuz W. et al. Absence of anti-human immunodeficiency virus types 1 and 2 seroconversion after the treatment of hemophilia A or von Willebrand’s disease with pasteurized factor VIII concentrate. N Engl J Med 1989; 321: 1148-52.
• 49 Schimpf K, Mannucci PM, Kreutz W. et al. Absence of hepatitis after treatment with a pasteurized factor VIII concentrate in patients with hemophilia and no previous transfusions. N Engl J Med 1987; 316: 918-22.
• 50 Schwaab R, Brackmann HH, Meyer C. et al. Haemophilia A: mutation type determines risk of inhibitor formation. Thromb Haemost 1995; 74: 1402-6.
• 51 Schwarz HP, Fischer M, Hopmeier P. et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-300.
• 52 Shapiro AD, Gilchrist GS, Hoots WK. et al. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery. Thromb Haemost 1998; 80: 773-8.
• 53 Sjamsoedin LJ, Heijnen L, Mauser-Bunschoten EP. et al. The effect of activated prothrombin-complex concentrate (FEIBA) on joint and muscle bleeding in patients with hemophilia A and antibodies to factor VIII. A double-blind clinical trial. N Engl J Med 1981; 305: 717-21.
• 54 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
• 55 Verstraete M, Prentice CR, Samama M. et al. A European view on the North American fifth consensus on antithrombotic therapy. Chest 2000; 117: 1755-70.
• 56 Vossen CY, Walker ID, Svensson P. et al. Recurrence rate after a first venous thrombosis in patients with familial thrombophilia. Arterioscler Thromb Vasc Biol 2005; 25: 1992-7.
• 57 Wells PS, Anderson DR, Bormanis J. et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997; 350 9094 1795-8.
• 58 Zeitler H, Ulrich-Merzenich G, Hess L. et al. Treatment of acquired hemophilia by the Bonn- Malmo Protocol: documentation of an in vivo immunomodulating concept. Blood 2005; 105: 2287-93.