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Hamostaseologie 1996; 16(03): 164-170
DOI: 10.1055/s-0038-1656651
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Schattauer GmbH

Spontane Faktor-VIII-Inhibitoren

Iris Huhmann
1   Universitätsklinik für Innere Medizin I, Abteilung für Hämatologie und Hämostaseologie (Leiter: Prof. Dr. K. Lechner), Universität Wien
,
K. Lechner
1   Universitätsklinik für Innere Medizin I, Abteilung für Hämatologie und Hämostaseologie (Leiter: Prof. Dr. K. Lechner), Universität Wien
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Publication History

Publication Date:
23 July 2018 (online)

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Zusammenfassung

Als spontane (nichthämophile) Faktor-Vlll-lnhibitoren werden Antikörper gegen Faktor VIII bei zuvor gerinnungsnormalen Patienten bezeichnet. Meist ist der F-Vlll-Mangel schwer und dementsprechend die Blutungsneigung ausgeprägt. Die Pathogenese ist heterogen. Laborchemisch findet sich typischerweise eine verlängerte aPTT und ein isolierter F-Vlll-Mangel. Die Antikörper sind polyklonal und zumeist Typ-Il-Inhibitoren. Die Therapie gliedert sich in die Beherrschung der akuten Blutung (hochkonzentrierte humane F-Vlll-Konzentrate, porciner F VIII, aktivierte Prothrombinkomplexpräparate, rekombinanter F Vlla, evtl. zusätzlich Plasmapherese und Immunadsorption - zur Reduktion des Inhibitors) und in die Langzeitreduktion des Titers mit Immunsuppressiva.

Schlüsselwörter

Spontane Faktor-VlIl-lnhibitoren - Hemmkörperhämophilie A - Diagnose - Therapie
 

  • LITERATUR

  • 1 Annichino-Bizzacchi JM, Machado TF. Leprosy and acquired factor VIII inhibitor: a case report. Lepr Rev 1991; 62 (02) 155-7
    PubMedSearch in Google Scholar
  • 2 Apter B, McCarthy V, Shapiro SS, Bailas SK. Successful preoperative apheresis of factor VIII antibody using factor VIII concentrate as a replacement fluid. J Clin Apheresis 1986; 3: 140
    CrossrefPubMedSearch in Google Scholar
  • 3 Ballard HS, Nyamuswa G. Life threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagulant coexisting with acquired autoantibodies against factor VIII. Br J Rheumatol. 1993; 32 (06) 515-7
    CrossrefPubMedSearch in Google Scholar
  • 4 Benandi M, Zaccaria A, Zinzani PL. et al Factor VIII inhibitor prior to and during secondary acute nonlymphocytic leukemia in a patient with cured Hodgkin's disease. Leuk Lymphoma 1995; 16: 5-6 511-3
    PubMedSearch in Google Scholar
  • 5 Berger JR, Rosenfeld WE, Sheremata WA. et al Chronic inflammatory polyradiculoneuropathy complicated by factor VIII antibody. Neurology 1983; 33: 1224-6
    CrossrefPubMedSearch in Google Scholar
  • 6 Berrut G, Shoaay I, Dupuis JM. et al Responses of autoimmune factor VIII inhibitors to a combination of cyclophosphamide and prednisone. Blood Coagul Fibrinolysis 1994; 5: 145-6
    CrossrefPubMedSearch in Google Scholar
  • 7 Brettler DB, Forsberg AD, Levine PH. et al The use of porcine factor VIII concentrate (Hyate: C) in the treatment of patients with inhibitor antibodies to factor VIII. Arch Int Med 1989; 149: 1381-5
    CrossrefPubMedSearch in Google Scholar
  • 8 Brodeur GMO', Neill PJ, Williams JA. Acquired inhibitors of coagulation in nonhemophiliac children. J Pediatr 1980; 96 (03) 439-41
    CrossrefPubMedSearch in Google Scholar
  • 9 Carreras LO, Perez GN, Xavier DL. et al Autoimmune factor VIII inhibitor responsive to gammaglobulin without in vitro neutralisation. Thromb Haemost 1988; 60 (02) 343
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Castaldi PA, Penny R. A macroglobulin with inhibitory activity against coagulation factor VIII. Blood 1970; 35: 370-6
    CrossrefPubMedSearch in Google Scholar
  • 11 Clyne L, Levy A. A high titre 'spontaneous' porvine factor VIII inhibitor. Thromb Haemost 1992; 68 (04) 475-6
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Dannhauser D, Casonato A, Pietrogrande F. et al Acquired factor VIII:C inhibitor in a patient with Sjogren's syndrome: successful treatment with steroid and immunosuppressive therapy. Acta Haematol 1994; 91 (02) 73-6
    CrossrefPubMedSearch in Google Scholar
  • 13 De La Fuente B, Panek S, Hoyer LW. The Effekt of 1-deamino 8 d-arginine vasopressin (DDAVP) in a nonhaemophilic patient with an acquired type II factor VIII inhibitor. Br J Haematol 1985; 59: 127-31
    CrossrefPubMedSearch in Google Scholar
  • 14 Devereux S, Fisher DM, Roter BLT. et al Factor VIII inhibitor and raised platelet IgG levels associated with methyldopa therapy. Br J Haematol 1983; 54: 485-8
    CrossrefPubMedSearch in Google Scholar
  • 15 Dietrich G, Algiman M. et al. Origin of antiidiotypic activity against factor VIII autoantibodies in pools of normal human Immunglobulin G (IVIg). Blood 1992; 79 (11) 2946-51
    PubMedSearch in Google Scholar
  • 16 Fischer M, Lechner K, Raith W. Hemmkörperhämophilie bei bullösem Pemphigoid (Lever). Hautarzt 1968; 19: 459-62
    PubMedSearch in Google Scholar
  • 17 Francesconi R, Korninger C, Thaler E. et al Plasmapheresis: Its value in the management of patients with antibodies to factor VIII. Haemostasis 1982; 11: 79-86
    PubMedSearch in Google Scholar
  • 18 Fulcher CA, Lechner K, Mahoney S de G. Immunoblot analysis shows changes in factor VIII inhibitor chain specifity in factor VIII inhibitor patients over time. Blood 1988; 72: 1348-56
    PubMedSearch in Google Scholar
  • 19 Ganly PS, Isaacs JD, Laffan MA. et al Acquired factor VIII inhibitor associated with lung abscess. BMJ 1987; 295: 811
    CrossrefPubMedSearch in Google Scholar
  • 20 Gianella-Borradori A, Hirt A, Liithy A. et al Haemophilia due to factor VIII inhibitors in a patient suffering from an autoimmune disease: Treatment with intravenous immunoglobulin. A case report. Blut 1984; 48: 403-7
    PubMedSearch in Google Scholar
  • 21 Gilles JG, Saint-Remy J-M R. Healthy subjects produce both antifactor VIII and specific anti-idiotypic antibodies. J Clin Invest 1994; 94: 1496-505
    CrossrefPubMedSearch in Google Scholar
  • 22 Glueck H. l, Coots MC, Benson M. et al A monoclonal immunoglobulin A (κ) factor VIII:C inhibitor associated with primary amyloidosis: Identification and characterization. J Lab Clin Med 1989; 113: 269-77
    PubMedSearch in Google Scholar
  • 23 Glueck HI, Hong R. A circulating anticoagulant in gamma-lA-multiple myeloma: its modification by penicillin. J Clin Invest 1965: 1866-81
    Search in Google Scholar
  • 24 Green D. Acquired factor VIII inhibitors and immunosuppression of autoantibodies. In:. Kessler C. (ed). Acquired hemophilia. Princeton: Excerpta medica Inc.; 1995: 25-40
    Search in Google Scholar
  • 25 Green D. Cytotoxic suppression of acquired factor VIIL:C inhibitors. Arn J Med 1991; 91 5A 14S-9S
    PubMedSearch in Google Scholar
  • 26 Green D. Immunosuppression of patients with acquired factor VIII inhibitors. Semin Hematol 1994; 31 2 suppl (Suppl. 04) 60-1
    PubMedSearch in Google Scholar
  • 27 Green D, Kwaan HC. An acquired factor VIII inhibitor responsive to high-dose gamma globulin. Thromb Haemost 1987; 58 (04) 1005-7
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemost 1981; 45 (03) 200-3
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Green D, Rademaker AW. et al A prospective randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII antibodies. Thromb Haemost 1993; 70: 753-7
    Thieme ConnectPubMedSearch in Google Scholar
  • 30 Hauser I, Schneider B, Lechner K. Postpartum factor VIII inhibitors. A review of the literature with special reference to the value of steroid and immunosuppressive treatment. Thromb Haemost 1995; 73 (01) 1-5
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Herbst KD, Rapaport S. l, Kenoyer DG. et al Syndrome of an acquired inhibitor to factor VIII responsive to cyclophosphamide and prednisone. Ann Intern Med 1981; 95: 575-8
    CrossrefPubMedSearch in Google Scholar
  • 32 Hoyer L, Scandella D. Factor VIII inhibitors: Structure and function in autoantibody and hemophilia A patients. Semin Hematol 1994; 31 2 suppl (Suppl. 04) 1-5
    PubMedSearch in Google Scholar
  • 33 Hoyle C, Ludlam CA. Acquired factor VIII inhibitor associated with multiple sclerosis, successfully treated with porcine factor VIII. Thromb Haemost 1987; 57 (02) 233
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Hultin MB. Acquired inhibitors in malignant and nonmalignant disease states. Am J Med 1991; 91 suppl 5A 9S-13S
    CrossrefPubMedSearch in Google Scholar
  • 35 Hultin MB, Hennessey J. The use of polyelectrolyte-fractionated porzine factor VIII in the treatment of a spontaneously acquired inhibitor to factor VIII. Thromb Res 1989; 55: 51-6
    CrossrefPubMedSearch in Google Scholar
  • 36 Inocentio De J, Lovell DJ, Gabriel CA. Acquired factor VIII inhibitor in juvenile rheumatoid arthritis. Pediatrics 1994; 94 4/1 550-3
    PubMedSearch in Google Scholar
  • 37 Ishikawa O, Tamura A, Ohnishi K. et al Pemphigus vulgaris associated with acquired hemophilia A due to factor VIII inhibitor. Acta Derm Venerol 1993; 73 (03) 229-30
    PubMedSearch in Google Scholar
  • 38 Kasper CK. Laboratory diagnosis of Factor VIII inhibitors. In:. Kessler C. (ed). Acquired hemophilia. Princeton: Excerpta medica Inc.; 1995: 9-24
    Search in Google Scholar
  • 39 Kasper CK. Raising factor VIII levels in patients with acquired factor VIII inhibitors. In: Acquired hemophilia. Kessler C. (ed). Princeton: Excerpta medica Inc.; 1995: 41-70
    Search in Google Scholar
  • 40 Kasper CK, Aledort L, Aronson D. et al A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34 (02) 612
    PubMedSearch in Google Scholar
  • 41 Kelsey PR, Leyland MJ. Acquired inhibitor to human factor VIII associated with paraproteinaemia and subsequent development of chronic lymphatic leukaemia. BMJ 1982; 285: 174-5
    CrossrefPubMedSearch in Google Scholar
  • 42 Kessler CM. An introduction to factor VIII inhibitors: The detection and quantitation. Am J Med 1991; 91 suppl 5A 1S-5S
    PubMedSearch in Google Scholar
  • 43 Kessler CM, Ludlam CA. The treatment of acquired factor VIII inhibitors: Worldwide experience with porcine factor VIII concentrate. Semin Hematol 1993; 30 2 suppl (Suppl. 01) 22-7
    PubMedSearch in Google Scholar
  • 44 Knöbl P, Derfler K, Korninger L. et al Elimination of acquired factor VIII antibodies by extracorporal antibody-based immuno adsorption (Ig-Therasorb®). Thromb Haemost 1995; 74 (04) 1350-8
    PubMedSearch in Google Scholar
  • 45 Komminoth A, Dufour P, Bergerat JP. et al Hairy cell leukemia and factor VIII inhibitor: a case report. Nouv Rev Fr Hematol 1992; 34 (03) 269-71
    PubMedSearch in Google Scholar
  • 46 Kondo H, Shigekiyo T, Kojima A. et al Acquired factor VIII inhibitor in a patient with adenocarcinoma of the lung. Jpn J Clin Oncol 1992; 22 (01) 49-53
    PubMedSearch in Google Scholar
  • 47 Koshihara K, Qian J, Lollar P. et al Immunoblot cross reactivity of factor VIII inhibitors with porcine factor VIII. Blood 1995; 86 (06) 2183-90
    PubMedSearch in Google Scholar
  • 48 Lechner K. Acquired inhibitors in nonhemophiliac patients. Haemostasis 1974; 3: 65-93
    PubMedSearch in Google Scholar
  • 49 Letizia C, Sellini M, Avvisati G. et al Acquired factor VIII inhibitor in a patient with adenocarcinoma of the colon-rectum. Ital J Gastroenterol 1991; 23 (02) 88-9
    PubMedSearch in Google Scholar
  • 50 Lian E C-Y, Larcada AF, Chiu E Y-Z. Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor. Ann Intern Med 1989; 110 (10) 774-8
    CrossrefPubMedSearch in Google Scholar
  • 51 Lin CK, Liang R, Liu HW. et al Myelodysplasic syndrome and acquired factor VIII inhibitor with severe subcutaneous hemorrhage. Acta Haematol 1991; 85 (04) 206-8
    CrossrefPubMedSearch in Google Scholar
  • 52 Lionnet F, Gouault-Heilmann M. Autoimmune factor VIII:C inhibitor durably responsive to immunoglobulin: A New Case. Thromb Haemost 1990; 64 (03) 488-9
    Thieme ConnectPubMedSearch in Google Scholar
  • 53 Lionnet F, Pulik M, Genet P. et al Acquired factor VIII inhibitor associated with a prostatic cancer: Simultaneous occurrence and healing. Thromb Haemost 1995; 73 (02) 327-8
    Thieme ConnectPubMedSearch in Google Scholar
  • 54 Lottenberg R, Kentro TB, Kitchens CS. Acquired Hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987; 147: 1077-81
    CrossrefPubMedSearch in Google Scholar
  • 55 Loutheroo W, Abrahm J, Schumacher Jr HR. Hemarthrosis in patients with acquired factor VIII inhibitor. Case Report. J Rheumatol 1991; 18 (01) 104-5
    PubMedSearch in Google Scholar
  • 56 Ludlam C, Morrison A, Kessler C. Treatment of acquired hemophilia. Semin Hematol 1994; 31 2 suppl (Suppl. 04) 16-9
    PubMedSearch in Google Scholar
  • 57 Lusher JM. Perspectives on the use of factor IX complex concentrates in the treatment of bleeding in persons with acquired factor VIII inhibition. Am J Med 1991; 91 5A 30S-4S
    PubMedSearch in Google Scholar
  • 58 Mateo J, Martino R, Borrell M. et al Acquired factor VIII inhibitor preceding chronic lymphocytic leukemia. Ann Hematol 1993; 67: 309-11
    CrossrefPubMedSearch in Google Scholar
  • 59 Moore MR, Poon MC, Williams RB. et al Acquired inhibitor to factor VIII (AHF) occuring with squamous cell carzinoma of the tongue. J La State Med Soc 1982; 134 (09) 23-4
    PubMedSearch in Google Scholar
  • 60 Morrison AE, Ludlam CA. Acquired haemophilia and its management. Annotation. Br J Haematol 1995; 89: 231-6
    CrossrefPubMedSearch in Google Scholar
  • 61 Morrison AE, Ludlam CA, Kessler C. Use of porcine factor VIII in the treatment of patients with acquired hemophilia. Blood 1993; 81 (06) 1513-20
    PubMedSearch in Google Scholar
  • 62 Mudad R, Kane WH. DDAVP in acquired hemophilia A: Case report and review of the literature. Am J Hematol 1993; 43: 295-9
    CrossrefPubMedSearch in Google Scholar
  • 63 Muhm M, Grois N, Kier P. et al 1-deamino- 8-d-arginine vasopressin in the treatment of non-haemophilic patients with acquired factor VIII inhibitor. Haemostasis 1990; 20: 15-20
    PubMedSearch in Google Scholar
  • 64 Naorose-Abidi SM, Bond LR, Chitolie A. et al Desmopressin therapy in patients with acquired factor VIII inhibitors. Lancet 1988; 13: 366
    PubMedSearch in Google Scholar
  • 65 Négrier C. The use of porcine factor VIII in France. Semin Hematol 1994; 31 2 suppl (Suppl. 04) 29-32
    PubMedSearch in Google Scholar
  • 66 Ng SC. Activated recombinant factor VII in the treatment of retroperitoneal haemorrhage in a patient with factor VIII inhibitor. Ann Acad Med Singapore 1994; 23 (06) 901-2
    PubMedSearch in Google Scholar
  • 67 Nilsson IM, Lamme S. On acquired hemophilia A. A survey of 11 cases. Acta Med Scand 1980; 208: 5-12
    PubMedSearch in Google Scholar
  • 68 Nilsson IM, Hedner U, Holmberg L. Suppression of factor VIII antibody by combined factor VIII and cyclophosphamide. Acta Med Scand 1974; 195: 65-72
    PubMedSearch in Google Scholar
  • 69 Nilsson IM, Jonsson S, Sundqvist SB. et al A procedure for removing high titer antibodies by extracorporeal protein-A-sepharose ad- sorption in hemophilia: Substitution therapy and surgery in a patient with hemophilia B and antibodies. Blood 1981; 58: 38-44
    PubMedSearch in Google Scholar
  • 70 Okamura T, Yamauchi Y, Fukuda T. et al Immunological analysis of acquired factor VIII inhibitor in a case with immunologic disorder. Acta Haematol 1991; 85 (03) 153-5
    CrossrefPubMedSearch in Google Scholar
  • 71 O' Reilly RA, Hamilton RD. Acquired hemophilia, meningeoma, and diphenylhydantoin therapy. J Neurosurg 1980; 53 (05) 600-5
    CrossrefPubMedSearch in Google Scholar
  • 72 Paraccini ML, Rocchini GM, Renoldi P. et al Acquired factor VIII inhibitor in a nonhaemophilic patient: Successful treatment with plasma exchange associated with factor VIII concentrate and immunosuppressors. Haemostasis 1984; 14: 249-52
    PubMedSearch in Google Scholar
  • 73 Poon MC, Saito H, Ratnoff OD. et al Techniques for demonstration of the specifity of circulating anticoagulants against antihemophilic factor (factor VIII), with studies of two cases possibly related to diphenylhydantoin therapy. Blood 1977; 49 (03) 477-82
    PubMedSearch in Google Scholar
  • 74 Preminger GM, Knupp CL. et al. Spontaneously acquired anti factor VIII antibodies: report of a patient with adenocarcinoma of the prostate. J Urol 1984; 31: 1182-4
    PubMedSearch in Google Scholar
  • 75 Preston FE, Dinsdale RCW, Sutcliffe DJ. et al Factor VIII inhibitor by-passing activity (FEIBA) in the management of patients with factor VIII inhibitors. Thromb Res 1977; 11: 643-51
    CrossrefPubMedSearch in Google Scholar
  • 76 Reimer G, Link I, Hauck H. Senear-Usher-Syndrom: Begleithämophilie durch das Auftreten eines Faktor-VIII-Hemmkörpers. Hautarzt 1982; 33 (12) 645-8
    PubMedSearch in Google Scholar
  • 77 Rodeghiero F, Castronovo S, Dini E. Disseminated intravascular coagulation after infusion of FEIBA (factor VIII inhibitor bypassing activity) in a patient with acquired haemophilia. Thromb Haemost 1982; 48 (03) 339-40
    Thieme ConnectPubMedSearch in Google Scholar
  • 78 Ruiz-Calderon AJ, Carrasco F, Duro R. et al Inhibidor adquirado del factor VIII en una paciente con arthritis rheumatoide. Sangre Barc 1993; 38 (05) 403-5
    PubMedSearch in Google Scholar
  • 79 Schwerdtfeger R, Hintz G, Huhn D. Successful treatment of a patient with postpartum factor VIII inhibitor with recombinant human interferon α 2a. Am J Hematol 1991; 37: 190-3
    CrossrefPubMedSearch in Google Scholar
  • 80 Scidler CW, Mills LE, Flowers MED. et al Spontaneous factor VIII inhibitor occuring in association with chronic graft-versus-host disease. Am J Hematol 1994; 45: 240-3
    CrossrefPubMedSearch in Google Scholar
  • 81 Shapiro SS. The immunologic character of acquired inhibitors of antihaemophilic globin (factor 8) and the kinetics of their interaction with factor 8. J Clin Invest 1967; 46 (02) 147-56
    CrossrefPubMedSearch in Google Scholar
  • 82 Shapiro SS, Huitín MB. Acquired inhibitors to the blood coagulation factors. Semin Thromb Haemost 1975; 1: 336
    PubMedSearch in Google Scholar
  • 83 Shastri KA, Logue GL, Zeid MY. et al Acquired factor VIII inhibitor in a patient with squamous carcinoma of the epiglottis. Arch Otolaryngol Head Neck Surg 1990; 116 (03) 350-3
    CrossrefPubMedSearch in Google Scholar
  • 84 Shurafa M, Raman S, Wollner I. Disappearance of factor VIII antibody after removal of primary colon adenocarcinoma. Am J Hematol 1995; 50: 149-50
    PubMedSearch in Google Scholar
  • 85 Singal U, Mammen EF. Concomitant occurrence of disseminated intravascular coagulation and factor VIII inhibitor in a patient with prostatic cancer. Am J Hematol 1987; 25: 237-42
    CrossrefPubMedSearch in Google Scholar
  • 86 Slocombe GW, Newland AC, Colvin MP. et al The role of intensive plasma exchange in the prevention and management of haemorrhage in patients with inhibitors to factor VIII. Br J Haematol 1981; 47: 577-85
    CrossrefPubMedSearch in Google Scholar
  • 87 Söhngen D, Köster W, Kuntz BME. et al Three cases of acquired factor VIII:C inhibitors in non-hemophilic patients. Klin Wochenschr 1990; 68: 1071-5
    CrossrefPubMedSearch in Google Scholar
  • 88 Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy for acquired F VIII inhibitors. Br J Haematol 1981; 48: 635-42
    PubMedSearch in Google Scholar
  • 89 Stricker RB, Barlogie B, Kiprov DD. Acquired factor VIII inhibitor associated with chronic interferon-alpha therapy. J Rheumatol 1994; 21 (02) 350-2
    PubMedSearch in Google Scholar
  • 90 Sultan Y, Kazatchkine MD, Nydegger U. et al Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors. Am J Med 1991; 91 5A 35S-9S
    PubMedSearch in Google Scholar
  • 91 Sultan Y, Maisonneuve P, Bismuth A. et al Successful management of a patient with an acquired factor VIII inhibitor. Transfusion 1983; 23: 62-4
    CrossrefPubMedSearch in Google Scholar
  • 92 Waddell CC, Lehane DE, Zubler MA. Acquired factor VIII inhibitor in a patient with mycosis fungoides. Cancer 1981; 47: 2901-3
    CrossrefPubMedSearch in Google Scholar
  • 93 Wajima T, Hall G. Factor VIII inhibitor in insulin-dependent diabetes mellitus. Am J Hematol 1989; 30: 186-7
    CrossrefPubMedSearch in Google Scholar
  • 94 Waltke EA, Jakobs SC, Hussey CV. et al Massive hematuria due to acquired factor VIII inhibitor. Urology 1981; 18 (06) 601-3
    CrossrefPubMedSearch in Google Scholar
  • 95 Weston Smith S G, Reveil P. The rapid development of an IgM inhibitor of porcine factor VIII in a patient with acquired haemophilia. Br J Haematol 1990; 75 (03) 434-6
    CrossrefPubMedSearch in Google Scholar