Post-Partum Factor VIII Inhibitors

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
• 2 Alexander B. Coagulation, haemorrhage and thrombosis. N Engl J Med 1955; 252: 484-494
• 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
• 4 Atanassov K, Hristova I. A case of a female patient with inhibitory hemophilia cured definitively. Folia medica plovdiv 1986; 28: 14-17
• 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
• 6 Barkhan P. Observations on a coagulation defect characterised by thrombocytopenia with a circulating anticoagulant. S Afr J Med Sci 1952; 17: 87-99
• 7 Biggs R, Macfarlane R. Human Blood Coagulation and its Disorders. Oxford: University Press; 1957: 286-304
• 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
• 9 Bruno MS, Brody HS. Hypothromboplastinemia associated with a circulating anticoagulant and hemorrhagic diathesis. Am J Med 1954; 16: 756-763
• 10 Chargaff E, West R. The biological significance of the thromboplastic protein of blood. J Biol Chem 1946; 166: 189-197
• 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
• 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
• 13 Dreskin OH, Rosenthal N. A hemophilia-like disease with prolonged coagulation time and a circulating anticoagulant. Blood 1950; 5: 46-60
• 14 Eckhardt AJ, Nicholas JT, Essig GF. Circulating anticoagulants as a cause of postpartum hemorrhage. Ohio St Med J 1970; 66: 1013-1015
• 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
• 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
• 17 Files JC, Morrison FS, Halbrook J. Post-partum treatment of a patient with a factor FVIII inhibitor. N Engl J Med 1981; 1650
• 18 Fiorina L. Hemorrhagic syndrome due to an inhibitor of antihemophilic globulin appearing after pregnancy. Acta Med Patav 1963; 23: 203-224
• 19 Fox GL, Tilson HB. Acquired hemophilia due to a circulating anticoagulant. J Oral Maxillofac Surg 1974; 32: 27-30
• 20 Frick PG. Hemophilia-like disease following pregnancy with transplacental transfer of an acquired circulating anticoagulant. Blood 1953; 8598-8608
• 21 Green D. Personal communication.
• 22 Greenwood RJ, Rabin SC. Hemophilia-like postpartum bleeding. Obstet Gynecol 1967; 30: 362-366
• 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
• 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
• 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
• 26 Hewlett JS, Haden RL. Hemophilia-like disease in women. J Lab Clin Med 1949; 34: 151-157
• 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
• 28 Hultin MB. Acquired inhibitors in malignant and nonmalignant disease states. Am J Med 1991; 5a suppl 9-13
• 29 Kitano K, Kawakami Y, Ijima Y, Kaji R. Intraperitoneal bleeding due to postpartum factor VIII inhibitor. Rinsho Ketsueki 1986; 27: 1668-1673
• 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
• 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
• 32 Lutze G, Canzler E, Presser HJ. Spontaner Gerinnungsfaktor-VIII:C-Inhibitor post partum - Ursache lebensbedrohlicher Blutung. Zentralbl Gynaekol 1989; 111: 167-172
• 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
• 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
• 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
• 36 Marengo-Rowe AJ, Murff G, Leveson JE, Cook J. Hemophilia-like disease associated with pregnancy. Obstet Gynecol 1972; 40: 56-64
• 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
• 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
• 39 Michiels JJ, Bosch LJ, Plas PM, Abels J. Factor VIII inhibitor postpartum. Scand J Haematol 1978; 20: 97-107
• 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
• 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
• 42 Naorose-Abidi SM, Bond LR, Chitolie A, Bevan DH. Desmopressin therapy in patients with acquired factor VIII inhibitors. Lancet 1988; 1: 366
• 43 Neidhardt B, Bartels O, Hahn B. Hemmkörperhämophilie A post partum. Dtsch Med Wochenschr 1985; 110: 799-802
• 44 Nilsson IM, Skanse B, Gydell K. Circulating anticoagulant after pregnancy and its response to ACTH. Acta Haematol 1958; 19: 40-50
• 45 O’Brien JR. An acquired coagulation defect in a woman. J Clin Pathol 1953; 6: 22-25
• 46 Ohkubo I, Mori Y, Deguchi A, Tsuda M. Factor VIII inhibitor postpartum. Rinsho Ketsueki 1986; 27: 1596-1602
• 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
• 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
• 49 Reece EA, Fox HE, Rapoport F. Factor VIII inhibitor: a cause of severe postpartum hemorrhage. Am J Obstet Gynecol 1982; 144: 985-987
• 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
• 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
• 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
• 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
• 54 Schultz W, Huang HD. Über eine erworbene hämorrhagische Diathese von Hämophiliecharakter. Dtsch Med Wochenschr 1943; 37/38: 665-667
• 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
• 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
• 57 Sherman LA, Goldstein MA, Sise HS. Circulating anticoagulant (antifactor VIII) treated with immunosuppressive drugs. Thromb Diath Haemorrh 1969; 21: 249-258
• 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
• 59 Shitamoto BS, Leslie KO, Galloway WB. Postpartum hemophilia. Am J Pathol 1982; 78: 789-791
• 60 Spero JA, Lewis JH U. Corticosteroid therapy for acquired FVIII : C inhibitors. Br J Haematol 1981; 48: 635-642
• 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
• 62 Takahashi Y, Fujimura Y, Sakai T, Shima M, Fukui H. A case of postpartum factor FVIII inhibitor. Rinsho Ketsueki 1983; 24: 468-475
• 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
• 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
• 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
• 66 Voke J, Letzky E. Pregnancy and antibody to factor VIII. J Clin Pathol 1977; 30: 928-932
• 67 Walpot L. Verworven hemofilie door een circulerend anticoagulans. Ned Tijdschr Geneeskd 1964; 108: 127-132
• 68 Zbinden J, Leupold R. Über Hemmkörperhämophilie. Schweiz Med Wochenschr 1957; 48: 1478-1480
• 69 Kasper CK. Treatment of factor VIII inhibitors. Prog Hemost Thromb 1989; 9: 57-86
• 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
• 71 Shapiro SS, Huitn M. Acquired inhibitors to the blood coagulation factors. Sem Thromb Hemostas 1975; 336-385
• 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
• 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