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Thromb Haemost 1995; 73(01): 001-005
DOI: 10.1055/s-0038-1651666
Review Article
Schattauer GmbH Stuttgart

Post-Partum Factor VIII Inhibitors

A Review of the Literature with Special Reference to the Value of Steroid and Immunosuppressive Treatment
I Hauser
1   The First Dept. of Internal Medicine, Division of Hematology and Blood Coagulation, University of Vienna, Vienna, Austria
,
B Schneider
2   The Institute of Medical Statistics and Documentation, University of Vienna, Vienna, Austria
,
K Lechner
1   The First Dept. of Internal Medicine, Division of Hematology and Blood Coagulation, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 03 May 1994

Accepted after resubmission 29 September 1994

Publication Date:
09 July 2018 (online)

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Summary

In a retrospective study 51 published cases of post-partum factor VIII inhibitors were analyzed with regard to the outcome according to treatment. The overall outcome was favorable with 97% survival at two years. The probability of complete remission (CR, absence of the inhibitor and normalization of factor VIII activity) was almost 100% at 30 months. Steroid treatment appears to be not superior to no treatment, but patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, 6-mercaptopurine) had a significantly shorter time to CR. In the absence of a randomized trial this analysis may be helpful for decision-making in women with factor VIII post-partum inhibitors. Because of the retrospective study design, conclusions have to be regarded with caution.

 

  • References

  • 1 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemost 1981; 45: 200-203
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Alexander B. Coagulation, haemorrhage and thrombosis. N Engl J Med 1955; 252: 484-494
    CrossrefPubMedGoogle Scholar
  • 3 Amamiya A, Hamada H, Yamada K, Meguro T. A case of woman with acquired factor VIII inhibitor after the delivery. Rinsho Ketsueki 1982; 23: 658-665
    PubMedGoogle Scholar
  • 4 Atanassov K, Hristova I. A case of a female patient with inhibitory hemophilia cured definitively. Folia medica plovdiv 1986; 28: 14-17
    PubMedGoogle Scholar
  • 5 Aviles A, Rangel B, Paz ReynaM, Pizzuto J. Inhibidor contra la fracción coagulante del factor VIII en el puerperio. Ginecol Obstet Mex 1986; 54: 152-154
    PubMedGoogle Scholar
  • 6 Barkhan P. Observations on a coagulation defect characterised by thrombocytopenia with a circulating anticoagulant. S Afr J Med Sci 1952; 17: 87-99
    PubMedGoogle Scholar
  • 7 Biggs R, Macfarlane R. Human Blood Coagulation and its Disorders. Oxford: University Press; 1957: 286-304
    Google Scholar
  • 8 Bloom AL, Davies AJ, Rees JK. A clinical and laboratory study of a patient with an unusual factor VIII inhibitor. Thromb Diath Haemorrh 1966; 15: 15-28
    PubMedGoogle Scholar
  • 9 Bruno MS, Brody HS. Hypothromboplastinemia associated with a circulating anticoagulant and hemorrhagic diathesis. Am J Med 1954; 16: 756-763
    CrossrefPubMedGoogle Scholar
  • 10 Chargaff E, West R. The biological significance of the thromboplastic protein of blood. J Biol Chem 1946; 166: 189-197
    CrossrefPubMedGoogle Scholar
  • 11 Coller BS, Hultin MB, Hoyer LW, Miller F, Dobbs JV, Dosik MH, Berger ER. Normal pregnancy in a patient with a prior postpartum factor VIII inhibitor: with observations on pathogenesis and prognosis. Blood 1981; 58: 619-624
    PubMedGoogle Scholar
  • 12 Conley CL, Ratnoff OD, Elliott CE, Hartmann RC. Studies on the initiation of blood coagulation. II. An anticoagulant inhibiting the activation of a plasma thromboplastic factor. J Clin Invest 1950; 29: 1182-1188
    CrossrefPubMedGoogle Scholar
  • 13 Dreskin OH, Rosenthal N. A hemophilia-like disease with prolonged coagulation time and a circulating anticoagulant. Blood 1950; 5: 46-60
    PubMedGoogle Scholar
  • 14 Eckhardt AJ, Nicholas JT, Essig GF. Circulating anticoagulants as a cause of postpartum hemorrhage. Ohio St Med J 1970; 66: 1013-1015
    PubMedGoogle Scholar
  • 15 Erskine JG, Burnett AK, Walker ID, Davidson JF. Plasma exchange in non-hemophilic patients with inhibitors to factor VIII C. BMJ 1981; 283: 760
    PubMedGoogle Scholar
  • 16 Fantl P, Nance MH. An acquired haemorrhagic disease in a female due to an inhibitor of blood coagulation. Med J Aust 1946; 2: 125-128
    PubMedGoogle Scholar
  • 17 Files JC, Morrison FS, Halbrook J. Post-partum treatment of a patient with a factor FVIII inhibitor. N Engl J Med 1981; 1650
    PubMedGoogle Scholar
  • 18 Fiorina L. Hemorrhagic syndrome due to an inhibitor of antihemophilic globulin appearing after pregnancy. Acta Med Patav 1963; 23: 203-224
    PubMedGoogle Scholar
  • 19 Fox GL, Tilson HB. Acquired hemophilia due to a circulating anticoagulant. J Oral Maxillofac Surg 1974; 32: 27-30
    PubMedGoogle Scholar
  • 20 Frick PG. Hemophilia-like disease following pregnancy with transplacental transfer of an acquired circulating anticoagulant. Blood 1953; 8598-8608
    PubMedGoogle Scholar
  • 21 Green D. Personal communication.
    PubMedGoogle Scholar
  • 22 Greenwood RJ, Rabin SC. Hemophilia-like postpartum bleeding. Obstet Gynecol 1967; 30: 362-366
    PubMedGoogle Scholar
  • 23 Haedicke G, O’Sullivan J, Seidler C, Donat W, Crowley JP. Tracheal obstruction after emergency tracheostomy in a patient with a postpartum factor VIII inhibitor. Crit Care Med 1990; 18: 449-450
    CrossrefPubMedGoogle Scholar
  • 24 Hauser I, Gisslinger H, Locker G, Elbl W, Kyrle PA, Pabinger I, Lechner K. Postpartum factor VIII inhibitors. Wien Klin Wochenschr 1993; 105355-105358
    PubMedGoogle Scholar
  • 25 Heinle RW, Weisberger AS. Hemorrhagic diathesis associated with low thromboplastic activity and a circulating anticoagulant (abstract). J Lab Clin Med 1949; 34: 1606-1607
    PubMedGoogle Scholar
  • 26 Hewlett JS, Haden RL. Hemophilia-like disease in women. J Lab Clin Med 1949; 34: 151-157
    PubMedGoogle Scholar
  • 27 Hudak C, Spiridonidis CH, Hart AJ, Betras SA, Laufman LR. Pregnancy-associated factor VIII inhibitor: Treatment with intravenous high-dose immunoglobulin. Am J Hematol 1993; 43: 158
    PubMedGoogle Scholar
  • 28 Hultin MB. Acquired inhibitors in malignant and nonmalignant disease states. Am J Med 1991; 5a suppl 9-13
    PubMedGoogle Scholar
  • 29 Kitano K, Kawakami Y, Ijima Y, Kaji R. Intraperitoneal bleeding due to postpartum factor VIII inhibitor. Rinsho Ketsueki 1986; 27: 1668-1673
    PubMedGoogle Scholar
  • 30 Lian EC Y, Larcada AF, Chiu AY Z. Combination immunosuppressive therapy after factor VIII infusion for acquired factor VIII inhibitor. Ann Intern Med 1989; 110: 774-778
    CrossrefPubMedGoogle Scholar
  • 31 Lottenberg R, Kentro TB. Acquired hemophilia, a natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987; 147: 1077-1081
    CrossrefPubMedGoogle Scholar
  • 32 Lutze G, Canzler E, Presser HJ. Spontaner Gerinnungsfaktor-VIII:C-Inhibitor post partum - Ursache lebensbedrohlicher Blutung. Zentralbl Gynaekol 1989; 111: 167-172
    PubMedGoogle Scholar
  • 33 Madison FW, Quick AJ. Hemophilia-like disease in the female with a note on the clotting time of the recalcified plasma. Am J Med Sci 1945; 209: 443-447
    CrossrefPubMedGoogle Scholar
  • 34 Majado MJ, Tamayo M, Funes C, Sánchez Penas A, Gonzáles García C, Sánchez Blanco JJ. Tres casos de inhibidor del factor VIII adquirido postparto. Sangre 1991; 36: 239-241
    PubMedGoogle Scholar
  • 35 Mamiya S, Nimura I. et al. Postpartum factor VIII inhibitor associated with primary biliary cirrhosis: a case report. J Jap Soc Int Med 1986; 75: 40-45
    PubMedGoogle Scholar
  • 36 Marengo-Rowe AJ, Murff G, Leveson JE, Cook J. Hemophilia-like disease associated with pregnancy. Obstet Gynecol 1972; 40: 56-64
    PubMedGoogle Scholar
  • 37 Margolius A, Dudley PJ, Ratnoff OD. Circulating anticoagulants: a study of 40 cases and a review of the literature. Medicine (Baltimore) 1961; 40: 145-202
    CrossrefPubMedGoogle Scholar
  • 38 Marwaha N, Sarode R, Chauhan AP, Varma JS, Dash S. Simultaneous occurrence of factor VIIIC inhibitor and antinuclear antibody in postpartum period. Am J Hematol 1991; 37: 49-50
    CrossrefPubMedGoogle Scholar
  • 39 Michiels JJ, Bosch LJ, Plas PM, Abels J. Factor VIII inhibitor postpartum. Scand J Haematol 1978; 20: 97-107
    PubMedGoogle Scholar
  • 40 Morrison JE, Ludlam CA. The use of porcine factor VIII in the treatment of patients with acquired hemophilia: the United Kingdom experience. Am J Med 1991 5 a suppl (Suppl. 05) A 23S-26S
    PubMedGoogle Scholar
  • 41 Nagura Y, Yanai M, Kanda A, Okada K, Maejima M, Maeda H, Inoue M, Takahashi S, Hatano M. Case of postpartum high titer of factor VIII inhibitor treated successfully by plasmapheresis. Nihon Univ J Med 1991; 33: 379-384
    PubMedGoogle Scholar
  • 42 Naorose-Abidi SM, Bond LR, Chitolie A, Bevan DH. Desmopressin therapy in patients with acquired factor VIII inhibitors. Lancet 1988; 1: 366
    PubMedGoogle Scholar
  • 43 Neidhardt B, Bartels O, Hahn B. Hemmkörperhämophilie A post partum. Dtsch Med Wochenschr 1985; 110: 799-802
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Nilsson IM, Skanse B, Gydell K. Circulating anticoagulant after pregnancy and its response to ACTH. Acta Haematol 1958; 19: 40-50
    CrossrefPubMedGoogle Scholar
  • 45 O’Brien JR. An acquired coagulation defect in a woman. J Clin Pathol 1953; 6: 22-25
    PubMedGoogle Scholar
  • 46 Ohkubo I, Mori Y, Deguchi A, Tsuda M. Factor VIII inhibitor postpartum. Rinsho Ketsueki 1986; 27: 1596-1602
    PubMedGoogle Scholar
  • 47 O’Sullivan JL, Haedicke GJ, Bevivino J. Spontaneous postpartum factor VIII inhibitor development with bleeding into the face and neck. J Oral Maxillofac Surg 1988; 84: 802-805
    PubMedGoogle Scholar
  • 48 Piana I, Magnin G, Sudan JP, Fogliani J, Siccardi F. Une cause rare d’hémorragie du post-partum: l’inhibiteur du facteur antihémophilique A. Rev Fr Gynecol Obstet 1972; 67: 621-624
    PubMedGoogle Scholar
  • 49 Reece EA, Fox HE, Rapoport F. Factor VIII inhibitor: a cause of severe postpartum hemorrhage. Am J Obstet Gynecol 1982; 144: 985-987
    CrossrefPubMedGoogle Scholar
  • 50 Robboy J, Lewis EJ, Schur PH, Colman RW. Circulating anticoagulants to factor VIII. Immunochemical studies and clinical response to factor VIII concentrates Am J Med 1970; 49: 742-752
    CrossrefPubMedGoogle Scholar
  • 51 Rolovics Z, Ruvidic R, Marinkovic N. Postpartum hemorrhage syndrome caused by factor VIII inhibitor in the blood. Bilten za hematologiju i transfuziju 1975; 3: 35-40
    PubMedGoogle Scholar
  • 52 Rosenthal N, Vogel P. Acquired haemophilia in a female. In Anniversary Volume for Robert Tilden Frank; by his colleagues, collaborators, associates and friends Geist SH. et al C. V. Mosby; St. Louis: 1937. quoted 66
    Google Scholar
  • 53 Sanchez-Foyos J, Outeirino J, Jiminez CasadoM, Pantagua G. Coagulopatias adquiridas por inactivation selectiva del factor VIII. Dos casos de “seudohemofilia” por anticoagulantes. Rev Clin Esp 1968; 110: 15-20
    PubMedGoogle Scholar
  • 54 Schultz W, Huang HD. Über eine erworbene hämorrhagische Diathese von Hämophiliecharakter. Dtsch Med Wochenschr 1943; 37/38: 665-667
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 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: 190-193
    CrossrefPubMedGoogle Scholar
  • 56 Shapiro SS. The immunologic character of acquired inhibitors of antihemophilic globulin (factor VIII) and the kinetics of their interaction with factor VIII. J Clin Invest 1967; 46: 147-156
    CrossrefPubMedGoogle Scholar
  • 57 Sherman LA, Goldstein MA, Sise HS. Circulating anticoagulant (antifactor VIII) treated with immunosuppressive drugs. Thromb Diath Haemorrh 1969; 21: 249-258
    PubMedGoogle Scholar
  • 58 Shinohara K, Sasaki H, Yamada K, Ishida Y, Kaneko T, Matsumoto N. A case with an inhibitor against factor VIII activity after the second postpartum. Rinso Ketsueki 1983; 24: 1670-1673
    PubMedGoogle Scholar
  • 59 Shitamoto BS, Leslie KO, Galloway WB. Postpartum hemophilia. Am J Pathol 1982; 78: 789-791
    PubMedGoogle Scholar
  • 60 Spero JA, Lewis JH U. Corticosteroid therapy for acquired FVIII : C inhibitors. Br J Haematol 1981; 48: 635-642
    PubMedGoogle Scholar
  • 61 Sultan Y, Kazatchkine MD, Maisonneuve P, Nydegger UE. Anti-idiotypic suppression of autoantibodies to factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin. Lancet 1984; 1: 765-768
    PubMedGoogle Scholar
  • 62 Takahashi Y, Fujimura Y, Sakai T, Shima M, Fukui H. A case of postpartum factor FVIII inhibitor. Rinsho Ketsueki 1983; 24: 468-475
    PubMedGoogle Scholar
  • 63 Tiarks C, Pechet L, Humphreys RE. Development of anti-idiotypic antibodies in a patient with a factor FVIII autoantibody. Am J Hematol 1989; 32: 217-21
    CrossrefPubMedGoogle Scholar
  • 64 Torregrosa MV, Ramos-Morales F, Pons E, Andino AM. Circulating anti-thromboplastic anticoagulant: ineffectiveness of cortisone and corticotropin. Am J Med Sei 1954; 228: 269-274
    CrossrefPubMedGoogle Scholar
  • 65 Vincente V, Alberca I, Gonzales R, Alegre A. Normal pregnancy in a patient with a postpartum factor VIII inhibitor. Am J Hematol 1987; 24: 107-109
    CrossrefPubMedGoogle Scholar
  • 66 Voke J, Letzky E. Pregnancy and antibody to factor VIII. J Clin Pathol 1977; 30: 928-932
    CrossrefPubMedGoogle Scholar
  • 67 Walpot L. Verworven hemofilie door een circulerend anticoagulans. Ned Tijdschr Geneeskd 1964; 108: 127-132
    PubMedGoogle Scholar
  • 68 Zbinden J, Leupold R. Über Hemmkörperhämophilie. Schweiz Med Wochenschr 1957; 48: 1478-1480
    PubMedGoogle Scholar
  • 69 Kasper CK. Treatment of factor VIII inhibitors. Prog Hemost Thromb 1989; 9: 57-86
    PubMedGoogle Scholar
  • 70 Morrison AE, Ludlam CA, Kessler C. Use of porcine factor VIII in the treatment of patients with acquired hemophilia. Blood 1993; 81: 1513-1520
    PubMedGoogle Scholar
  • 71 Shapiro SS, Huitn M. Acquired inhibitors to the blood coagulation factors. Sem Thromb Hemostas 1975; 336-385
    PubMedGoogle Scholar
  • 72 Herbst KD, Rapaport SI, Kenoyer DG, Stanton W, Feinstein DI. Syndrome of an acquired inhibitor of factor VIII responsive to cyclophosphamide and prednisone. Ann Int Med 1981; 95: 575-578
    CrossrefPubMedGoogle Scholar
  • 73 Green D, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of factor VIII autoantibodies. Thromb Haemost 1993; 69: A57
    PubMedGoogle Scholar