Erworbene Inhibitoren gegen Faktor IX

Zusammenfassung

Spontan erworbene Faktor-IX-Hemmkörper treten sehr selten auf, wesentlich seltener als spontan erworbene Faktor-Vlll-Hemmkörper. Die durch sie verursachte Blutungsneigung ist ähnlich derjenigen, die durch Faktor-Vlll-Hemmkörper induziert werden kann. Auch die Grundkrankheiten sind ähnlich denen, die bei den spontanen Faktor-Vlll-Hemmkörpem vorliegen.

Die Diagnose erfolgt mit Hilfe der Bethesda-Methode. Lupus-Antikoagulanzien sollten vorher ausgeschlossen werden. Faktor-IX-Hemmkörper sind nicht so ausgeprägt temperatur- und zeitabhängig wie Faktor-Vlll-Inhibitoren. Sie weisen keine komplexe Kinetik auf. Meist sind es Immunglobuline der IgG-Klasse 1-4. Die Blutstillungstherapie kann mit Feiba® oder rekombinantem Faktor Vila erfolgen. Durch Plasmapheresen kann die Titerhöhe reduziert werden. Zur Elimination empfiehlt sich eine immunsuppressive Therapie, zum Beispiel eine Kombination von Cyclophosphamid und Kortikosteroiden.

Schlüsselwörter

Faktor-IX-Hemmkörper - postpartale Hemmkörper - Bethesda-Methode - Blutstillungstherapie - Eliminationstherapie

• LITERATUR

• 1 Castro O, Farber LR, Clyne LP. Circulating anticoagulants against FIX and XI in systemic lupus erythematosus. Ann Int Med 1972; 77: 543-8
• 2 Collins HW, Gonzales MF. Acquired factor IX inhibitor in a patient with adenocarcinoma of the colon. Acta Haematol 1984; 71: 49
• 3 Doughty HA, Northeast A, Sklair L. et al The use of recombinant factor VIIa in a patient with acquired haemophilia A undergoing surgery. Blood Coagul Fibrinol 1995; 6: 125-8
• 4 Formanek G. Hemofilia a hémofilne stavy u zien. Casopis Lekaru Ceskych 1957; 96: 1001
• 5 Gadarowski JJ, Gzypek EE, Ontiveros JD, Pedraza IL. Modification of the Bethesda assay for factor VIII or IX inhibitors to improve efficiency. Acta Haematol 1988; 134-8
• 6 Giddings JC, Bloom AL, Kelly MA, Spratt HC. Human factor IX inhibitors: Immunochemical characteristics and treatment with activated concentrate. Clin Lab Haematol 1983; 5: 165
• 7 Green D. Immunosuppression of factor VIII inhibitors in nonhemophilic patients. Semin Hematol 1993; 30 Suppl 28-31
• 8 Hambley H, Watkins R, Tansey PA. et al Plasmapheresis and factor VIIIC inhibitors. Lancet 1985; 1: 274
• 9 Hocking DR. Acquired coagulation factor deficiencies. Med J Aust 1970; 1: 659
• 10 Kasper CK, Aledort LM, Counts RB. et al A more uniform measurement of factor VIII inhibitors. Thromb Diath Heamorrh 1975; 34: 869-72
• 11 Knöbl P, Derfler K, Korninger L. et al Elimination of acquired factor VIII inhibitors with immunglobuline-apheresis. Poster no. 143, GTH. 15.-18.2.1995; Berlin. Ann Hematol 1995; 70 (Suppl. 01) A36
• 12 Largo R, Sigg P, von Feiten A, Straub PW. Acquired factor IX inhibitor in a nonhaemophilic patient with autoimmune disease. Br J Haematol 1974; 26: 129
• 13 Lechner K. Factor IX inhibitors. Report of two cases and a study of the biological, chemical and immunological properties of the inhibitors. Thromb Haemost 1971; 25: 447-60
• 14 Lechner K. Acquired inhibitors in nonhemophiliac patients. Haemostasis 1974; 3: 65
• 15 Lewis RM, Reisner HM, Chung KS, Roberts HR. Detection of factor IX antibodies by radioimmunoassay: effect of calcium on antibody-factor IX interaction. Blood 1980; 56: 608-14
• 16 Ljung R, Holmberg L. Detection of factor IX inhibitors by immunoradiometric assay. Acta Haematol 1983; 70: 307-11
• 17 Miller K, Neely JC, Krivit W, Edson JR. Spontaneously acquired factor IX inhibitor in a nonhemophiliac child. J Pediatr 1978; 93: 232-4
• 18 Moake J. l, Kent CJ, Meta LD, Wright LC. Circulating IgG antibodies against factors IX and VIII in multiple sclerosis. Acta Haematol 1976; 55: 53
• 19 Morrison AE, Ludlam CA. Acquired haemophilia and its management. Br J Haematol 1995; 89: 231-6
• 20 Nilsson IM, Berntorp E, Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide and factor VIII. N Engl J Med 1981; 15: 947-50
• 21 Orstavik KH, Nilsson IM. A study of acquired inhibitors of factor IX by means of precipitating rabbit antisera against factor IX. Thromb Res 1978; 12: 863-74
• 22 Orstavik KH, Orstavik I. Enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to factor IX in hemophilia B. Thromb Res 1981; 22: 253-7
• 23 Ozsoylu S, Ozer FL. Acquired factor IX deficiency. Acta Haematol 1973; 50: 305
• 24 Pike IM, Yount WJ, Puritz EM, Roberts HR. Immunochemical characterization of a monoclonal TG4 human antibody to factor IX. Blood 1971; 25: 447
• 25 Reisner MM, Roberts HR, Krumholz S, Young WJ. Immunochemical characterization of a polyclonal human antibody to factor IX. Blood 1977; 50: 11
• 26 Roberts HR, Cromartie R. Overview of inhibitors to factor VIII and IX. Prog Clin Biol Res 1984; 150: 1-18
• 27 Ross F. Auto immunocoagulopatia da anticorpo antifattore IX (PTC). Folia Allerg (Roma) 1969; 16: 13
• 28 Sanchez-Medal L, Lisker R, Lopez ET. Unusual circulating anticoagulant in a patient with systemic lupus erythematosus. Acta Haematol 1963; 29: 117
• 29 Sarode R, Chauhan AP, Marwaha N. et al Time dependent factor IX inhibitor. Thromb Haemost 1989; 62 (04) 1151
• 30 Scharrer I. Erworbene Antikörper gegen Gerinnungsfaktoren. Hämostaseologie 1986; 6: 89-92
• 31 Schwertfeger R, Hintz G, Huhn D. Successful treatment of a patient with postpartum factor VIII inhibitor with recombinant human Interferon alfa 2a. Am J Hematol 1991; 37: 190-3
• 32 Seremetis SV. The clinical use of factor VIIa in the treatment of factor VIII inhibitor patients. Semin Hematol 1994; 31 (Suppl. 04) 53-5
• 33 Shapiro SS, Hultin M. Acquired inhibitors to the blood coagulation factor. Semin Thromb Heamost 1975; 1: 336
• 34 Sultan MD, Kazatchkine MD, Algiman M. et al The use of intravenous immunoglobulins in the treatment of factor VIII inhibitors. Semin Hematol 1994; 31 (Suppl. 04) 65-6