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Acquired inhibitors of coagulation

INTRODUCTION

Acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor.

Some disorders may be associated with antibodies to a variety of clotting factors. In systemic lupus erythematosus, for example, antiphospholipid antibodies and antibodies directed against factors II, VIII, IX, XI, XII, and XIII have been described [1]. (See "Hematologic manifestations of systemic lupus erythematosus in adults", section on 'Antibodies to clotting factors and phospholipids' and "Clinical manifestations of the antiphospholipid syndrome", section on 'Other antiphospholipid antibodies'.)

Antiphospholipid antibodies represent a special problem; these antibodies prolong certain clotting assays, but result in thrombosis rather than bleeding. The pathogenesis, diagnosis, and treatment of conditions associated with antiphospholipid antibodies are discussed elsewhere in UpToDate. (See "Pathogenesis of the antiphospholipid syndrome" and "Clinical manifestations of the antiphospholipid syndrome" and "Treatment of the antiphospholipid syndrome".)

A common clinical manifestation in affected patients is a hemorrhagic diathesis. Acquired coagulation inhibitors that lead to bleeding will be reviewed here. The natural history and management of these inhibitors are quite different from inhibition due to alloantibodies that occur in patients with various inherited bleeding disorders (eg, congenital deficiencies of factors VIII, IX, or XI) treated with factor replacement. The latter problem is discussed separately. (See "Factor VIII and factor IX inhibitors in patients with hemophilia" and "Factor XI deficiency", section on 'FXI inhibitors'.)

FACTOR VIII INHIBITORS

The most common autoantibodies that affect clotting factor activity and lead to a bleeding disorder are directed against, and interfere with, the activity of factor VIII, a condition also called acquired hemophilia A [2-6]. Although there are no large series describing the immunoglobulin class of the factor VIII autoantibodies, most have been IgG antibodies that do not bind complement.

                           

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Literature review current through: Oct 2014. | This topic last updated: Nov 11, 2014.
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References
Top
  1. Laurence J, Wong JE, Nachman R. The cellular hematology of systemic lupus erythematosus. In: Systemic Lupus Erythematosus, 2nd ed, Lahita RG (Ed), Churchill Livingstone, New York 1992.
  2. Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost 1981; 45:200.
  3. Hauser I, Schneider B, Lechner K. Post-partum factor VIII inhibitors. A review of the literature with special reference to the value of steroid and immunosuppressive treatment. Thromb Haemost 1995; 73:1.
  4. Franchini M, Gandini G, Di Paolantonio T, Mariani G. Acquired hemophilia A: a concise review. Am J Hematol 2005; 80:55.
  5. Key NS. Inhibitors in congenital coagulation disorders. Br J Haematol 2004; 127:379.
  6. Franchini M, Mannucci PM. Acquired haemophilia A: a 2013 update. Thromb Haemost 2013; 110:1114.
  7. Mahendra A, Padiolleau-Lefevre S, Kaveri SV, Lacroix-Desmazes S. Do proteolytic antibodies complete the panoply of the autoimmune response in acquired haemophilia A? Br J Haematol 2012; 156:3.
  8. Fulcher CA, de Graaf Mahoney S, Zimmerman TS. FVIII inhibitor IgG subclass and FVIII polypeptide specificity determined by immunoblotting. Blood 1987; 69:1475.
  9. Fulcher CA, Lechner K, de Graaf Mahoney S. Immunoblot analysis shows changes in factor VIII inhibitor chain specificity in factor VIII inhibitor patients over time. Blood 1988; 72:1348.
  10. Moreau A, Lacroix-Desmazes S, Stieltjes N, et al. Antibodies to the FVIII light chain that neutralize FVIII procoagulant activity are present in plasma of nonresponder patients with severe hemophilia A and in normal polyclonal human IgG. Blood 2000; 95:3435.
  11. Prescott R, Nakai H, Saenko EL, et al. The inhibitor antibody response is more complex in hemophilia A patients than in most nonhemophiliacs with factor VIII autoantibodies. Recombinate and Kogenate Study Groups. Blood 1997; 89:3663.
  12. Arai M, Scandella D, Hoyer LW. Molecular basis of factor VIII inhibition by human antibodies. Antibodies that bind to the factor VIII light chain prevent the interaction of factor VIII with phospholipid. J Clin Invest 1989; 83:1978.
  13. Scandella D, Gilbert GE, Shima M, et al. Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site. Blood 1995; 86:1811.
  14. Pratt KP, Shen BW, Takeshima K, et al. Structure of the C2 domain of human factor VIII at 1.5 A resolution. Nature 1999; 402:439.
  15. Ortel TL, Moore KD, Quinn-Allen MA, et al. Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations. Blood 1998; 91:4188.
  16. Ortel TL, Quinn-Allen MA, Charles LA, et al. Characterization of an acquired inhibitor to coagulation factor V. Antibody binding to the second C-type domain of factor V inhibits the binding of factor V to phosphatidylserine and neutralizes procoagulant activity. J Clin Invest 1992; 90:2340.
  17. Macedo-Ribeiro S, Bode W, Huber R, et al. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature 1999; 402:434.
  18. Collins P, Macartney N, Davies R, et al. A population based, unselected, consecutive cohort of patients with acquired haemophilia A. Br J Haematol 2004; 124:86.
  19. Collins PW, Hirsch S, Baglin TP, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood 2007; 109:1870.
  20. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol 2003; 121:21.
  21. Franchini M. Postpartum acquired factor VIII inhibitors. Am J Hematol 2006; 81:768.
  22. Tengborn L, Baudo F, Huth-Kühne A, et al. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG 2012; 119:1529.
  23. Green D, Schuette PT, Wallace WH. Factor VIII antibodies in rheumatoid arthritis. Effect of cyclophosphamide. Arch Intern Med 1980; 140:1232.
  24. Soriano RM, Matthews JM, Guerado-Parra E. Acquired haemophilia and rheumatoid arthritis. Br J Rheumatol 1987; 26:381.
  25. Lafferty TE, Smith JB, Schuster SJ, DeHoratius RJ. Treatment of acquired factor VIII inhibitor using intravenous immunoglobulin in two patients with systemic lupus erythematosus. Arthritis Rheum 1997; 40:775.
  26. 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; 32:515.
  27. Hauser I, Lechner K. Solid tumors and factor VIII antibodies. Thromb Haemost 1999; 82:1005.
  28. Tiplady CW, Hamilton PJ, Galloway MJ. Acquired haemophilia complicating the remission of a patient with high grade non-Hodgkin's lymphoma treated by fludarabine. Clin Lab Haematol 2000; 22:163.
  29. English KE, Brien WF, Howson-Jan K, Kovacs MJ. Acquired factor VIII inhibitor in a patient with chronic myelogenous leukemia receiving interferon-alfa therapy. Ann Pharmacother 2000; 34:737.
  30. Komminoth A, Dufour P, Bergerat JP, et al. Hairy cell leukemia and factor VIII inhibitor: a case report. Nouv Rev Fr Hematol 1992; 34:269.
  31. Sallah S, Wan JY. Inhibitors against factor VIII associated with the use of interferon-alpha and fludarabine. Thromb Haemost 2001; 86:1119.
  32. Delyon J, Mateus C, Lambert T. Hemophilia A induced by ipilimumab. N Engl J Med 2011; 365:1747.
  33. Sallah S, Wan JY. Inhibitors against factor VIII in patients with cancer. Analysis of 41 patients. Cancer 2001; 91:1067.
  34. Sborov DW, Rodgers GM. Acquired hemophilia a: a current review of autoantibody disease. Clin Adv Hematol Oncol 2012; 10:19.
  35. Lossing TS, Kasper CK, Feinstein DI. Detection of factor VIII inhibitors with the partial thromboplastin time. Blood 1977; 49:793.
  36. Kasper CK, Aledort L, Aronson D, et al. Proceedings: A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34:612.
  37. Krudysz-Amblo J, Parhami-Seren B, Butenas S, et al. Quantitation of anti-factor VIII antibodies in human plasma. Blood 2009; 113:2587.
  38. Hay CR, Brown S, Collins PW, et al. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation. Br J Haematol 2006; 133:591.
  39. Collins PW. Treatment of acquired hemophilia A. J Thromb Haemost 2007; 5:893.
  40. Collins PW, Percy CL. Advances in the understanding of acquired haemophilia A: implications for clinical practice. Br J Haematol 2010; 148:183.
  41. Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood 2008; 112:250.
  42. Lusher JM. Recombinant factor VIIa (NovoSeven) in the treatment of internal bleeding in patients with factor VIII and IX inhibitors. Haemostasis 1996; 26 Suppl 1:124.
  43. Scharrer I. Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency. Haemophilia 1999; 5:253.
  44. Liebman HA, Chediak J, Fink KI, et al. Activated recombinant human coagulation factor VII (rFVIIa) therapy for abdominal bleeding in patients with inhibitory antibodies to factor VIII. Am J Hematol 2000; 63:109.
  45. Sallah S. Treatment of acquired haemophilia with factor eight inhibitor bypassing activity. Haemophilia 2004; 10:169.
  46. Hay CR, Negrier C, Ludlam CA. The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study. Thromb Haemost 1997; 78:1463.
  47. Sumner MJ, Geldziler BD, Pedersen M, Seremetis S. Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia 2007; 13:451.
  48. Holme PA, Brosstad F, Tjønnfjord GE. Acquired haemophilia: management of bleeds and immune therapy to eradicate autoantibodies. Haemophilia 2005; 11:510.
  49. Baudo F, Collins P, Huth-Kühne A, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood 2012; 120:39.
  50. Kessler CM. New perspectives in hemophilia treatment. Hematology Am Soc Hematol Educ Program 2005; :429.
  51. Gandini G, Franchini M, Manzato F, et al. A combination of prednisone, high-dose intravenous immunoglobulin and desmopressin in the treatment of acquired hemophilia A with high-titer inhibitor. Haematologica 1999; 84:1054.
  52. Franchini M, Girelli D, Olivieri O, et al. Clinical heterogeneity of acquired hemophilia A: a description of 4 cases. Haematologica 2005; 90:ECR16.
  53. Morrison AE, Ludlam CA, Kessler C. Use of porcine factor VIII in the treatment of patients with acquired hemophilia. Blood 1993; 81:1513.
  54. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm420263.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on October 24, 2014).
  55. Zakas PM, Vanijcharoenkarn K, Markovitz RC, et al. Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors. J Thromb Haemost 2014.
  56. Collins P, Baudo F, Knoebl P, et al. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood 2012; 120:47.
  57. Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost 1993; 70:753.
  58. Schwartz RS, Gabriel DA, Aledort LM, et al. A prospective study of treatment of acquired (autoimmune) factor VIII inhibitors with high-dose intravenous gammaglobulin. Blood 1995; 86:797.
  59. Wiestner A, Cho HJ, Asch AS, et al. Rituximab in the treatment of acquired factor VIII inhibitors. Blood 2002; 100:3426.
  60. Kain S, Copeland TS, Leahy MF. Treatment of refractory autoimmune (acquired) haemophilia with anti-CD20 (rituximab). Br J Haematol 2002; 119:578.
  61. Stasi R, Brunetti M, Stipa E, Amadori S. Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia. Blood 2004; 103:4424.
  62. Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol 2007; 63:47.
  63. Sperr WR, Lechner K, Pabinger I. Rituximab for the treatment of acquired antibodies to factor VIII. Haematologica 2007; 92:66.
  64. Field JJ, Fenske TS, Blinder MA. Rituximab for the treatment of patients with very high-titre acquired factor VIII inhibitors refractory to conventional chemotherapy. Haemophilia 2007; 13:46.
  65. Franchini M, Veneri D, Lippi G, Stenner R. The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders. Thromb Haemost 2006; 96:119.
  66. Onitilo AA, Skorupa A, Lal A, et al. Rituximab in the treatment of acquired factor VIII inhibitors. Thromb Haemost 2006; 96:84.
  67. Garvey B. Rituximab in the treatment of autoimmune haematological disorders. Br J Haematol 2008; 141:149.
  68. Boles JC, Key NS, Kasthuri R, Ma AD. Single-center experience with rituximab as first-line immunosuppression for acquired hemophilia. J Thromb Haemost 2011; 9:1429.
  69. Schulman S, Langevitz P, Livneh A, et al. Cyclosporine therapy for acquired factor VIII inhibitor in a patient with systemic lupus erythematosus. Thromb Haemost 1996; 76:344.
  70. Brox AG, Laryea H, Pelletier M. Successful treatment of acquired factor VIII inhibitors with cyclosporin. Am J Hematol 1998; 57:87.
  71. Maclean PS, Tait RC, Lowe GD, et al. Successful elimination of factor VIII inhibitor using cyclosporin A. Br J Haematol 2003; 122:1024.
  72. Petrovic M, Derom E, Baele G. Cyclosporine treatment of acquired hemophilia due to factor VIII antibodies. Haematologica 2000; 85:895.
  73. Sallah S, Wan JY. Efficacy of 2-chlorodeoxyadenosine in refractory factor VIII inhibitors in persons without hemophilia. Blood 2003; 101:943.
  74. Jansen M, Schmaldienst S, Banyai S, et al. Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb). Br J Haematol 2001; 112:91.
  75. Freedman J, Rand ML, Russell O, et al. Immunoadsorption may provide a cost-effective approach to management of patients with inhibitors to FVIII. Transfusion 2003; 43:1508.
  76. 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.
  77. 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.
  78. Coller BS, Hultin MB, Hoyer LW, et al. Normal pregnancy in a patient with a prior postpartum factor VIII inhibitor: with observations on pathogenesis and prognosis. Blood 1981; 58:619.
  79. Scully MF, Shublaq W, Oliver GD. Acquired hemophilia a presenting as a bleeding diathesis in a postpartum patient: diagnosis and management. J Obstet Gynaecol Can 2002; 24:430.
  80. Mytopher K, Dudebout J, Card R, Gilliland B. Acquired hemophilia A presenting post partum. CMAJ 2007; 177:339.
  81. Shurafa M, Raman S, Wollner I. Disappearance of factor VIII antibody after removal of primary colon adenocarcinoma. Am J Hematol 1995; 50:149.
  82. Lollar P. Pathogenic antibodies to coagulation factors. Part II. Fibrinogen, prothrombin, thrombin, factor V, factor XI, factor XII, factor XIII, the protein C system and von Willebrand factor. J Thromb Haemost 2005; 3:1385.
  83. Bajaj SP, Rapaport SI, Fierer DS, et al. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. Blood 1983; 61:684.
  84. Vivaldi P, Rossetti G, Galli M, Finazzi G. Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome. Case report and review of literature. Haematologica 1997; 82:345.
  85. Erkan D, Bateman H, Lockshin MD. Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature. Lupus 1999; 8:560.
  86. Bajaj SP, Rapaport SI, Barclay S, Herbst KD. Acquired hypoprothrombinemia due to non-neutralizing antibodies to prothrombin: mechanism and management. Blood 1985; 65:1538.
  87. Flaherty MJ, Henderson R, Wener MH. Iatrogenic immunization with bovine thrombin: a mechanism for prolonged thrombin times after surgery. Ann Intern Med 1989; 111:631.
  88. Ortel TL, Charles LA, Keller FG, et al. Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum and laboratory diagnosis. Am J Hematol 1994; 45:128.
  89. Zehnder JL, Leung LL. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 1990; 76:2011.
  90. Bänninger H, Hardegger T, Tobler A, et al. Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V. Br J Haematol 1993; 85:528.
  91. Knöbl P, Lechner K. Acquired factor V inhibitors. Baillieres Clin Haematol 1998; 11:305.
  92. LOELIGER A, HERS JF. Chronic antithrombinaemia (Antithrombin V) with Haemorrhagic diathesis in a case of rheumatoid arthritis with hypergammaglobulinaemia). Thromb Diath Haemorrh 1957; 1:499.
  93. Scully MF, Ellis V, Kakkar VV, et al. An acquired coagulation inhibitor to factor II. Br J Haematol 1982; 50:655.
  94. Gabriel DA, Carr ME, Cook L, Roberts HR. Spontaneous antithrombin in a patient with benign paraprotein. Am J Hematol 1987; 25:85.
  95. La Spada AR, Skålhegg BS, Henderson R, et al. Brief report: fatal hemorrhage in a patient with an acquired inhibitor of human thrombin. N Engl J Med 1995; 333:494.
  96. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion 2002; 42:18.
  97. Nesheim ME, Nichols WL, Cole TL, et al. Isolation and study of an acquired inhibitor of human coagulation factor V. J Clin Invest 1986; 77:405.
  98. Tracy PB, Giles AR, Mann KG, et al. Factor V (Quebec): a bleeding diathesis associated with a qualitative platelet Factor V deficiency. J Clin Invest 1984; 74:1221.
  99. Tarantino MD, Ross MP, Daniels TM, Nichols WL. Modulation of an acquired coagulation factor V inhibitor with intravenous immune globulin. J Pediatr Hematol Oncol 1997; 19:226.
  100. de Raucourt E, Barbier C, Sinda P, et al. High-dose intravenous immunoglobulin treatment in two patients with acquired factor V inhibitors. Am J Hematol 2003; 74:187.
  101. Navarrete MA, van der Meer FJ, Damiani G, et al. The use of rituximab therapy in patients with acquired factor V inhibitors. Am J Hematol 2012; 87:826.
  102. Campbell E, Sanal S, Mattson J, et al. Factor VII inhibitor. Am J Med 1980; 68:962.
  103. Weisdorf D, Hasegawa D, Fair DS. Acquired factor VII deficiency associated with aplastic anaemia: correction with bone marrow transplantation. Br J Haematol 1989; 71:409.
  104. Delmer A, Horellou MH, Andreu G, et al. Life-threatening intracranial bleeding associated with the presence of an antifactor VII autoantibody. Blood 1989; 74:229.
  105. Okajima K, Ishii M. Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency. Int J Hematol 1999; 69:129.
  106. Miller K, Neely JE, Krivit W, Edson JR. Spontaneously acquired factor IX inhibitor in a nonhemophiliac child. J Pediatr 1978; 93:232.
  107. Mazzucconi MG, Peraino M, Bizzoni L, et al. Acquired inhibitor against factor IX in a child: successful treatment with high-dose immunoglobulin and dexamethasone. Haemophilia 1999; 5:132.
  108. Largo R, Sigg P, von Felten A, Straub PW. Acquired factor-IX inhibitor in a nonhaemophilic patient with autoimmune disease. Br J Haematol 1974; 26:129.
  109. Berman BW, McIntosh S, Clyne LP, et al. Spontaneously acquired Factor IX inhibitors in childhood. Am J Pediatr Hematol Oncol 1981; 3:77.
  110. Mulhare PE, Tracy PB, Golden EA, et al. A case of acquired factor X deficiency with in vivo and in vitro evidence of inhibitor activity directed against factor X. Am J Clin Pathol 1991; 96:196.
  111. Lankiewicz MW, Bell WR. A unique circulating inhibitor with specificity for coagulation factor X. Am J Med 1992; 93:343.
  112. Rao LV, Zivelin A, Iturbe I, Rapaport SI. Antibody-induced acute factor X deficiency: clinical manifestations and properties of the antibody. Thromb Haemost 1994; 72:363.
  113. Furie B, Greene E, Furie BC. Syndrome of acquired factor X deficiency and systemic amyloidosis in vivo studies of the metabolic fate of factor X. N Engl J Med 1977; 297:81.
  114. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood 2001; 97:1885.
  115. Ericson S, Shah N, Liberman J, Aboulafia DM. Fatal bleeding due to acquired factor IX and X deficiency: a rare complication of primary amyloidosis; case report and review of the literature. Clin Lymphoma Myeloma Leuk 2014; 14:e81.
  116. Mumford AD, O'Donnell J, Gillmore JD, et al. Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis. Br J Haematol 2000; 110:454.
  117. Reece EA, Clyne LP, Romero R, Hobbins JC. Spontaneous factor XI inhibitors. Seven additional cases and a review of the literature. Arch Intern Med 1984; 144:525.
  118. Vercellotti GM, Mosher DF. Acquired factor XI deficiency in systemic lupus erythematosus. Thromb Haemost 1982; 48:250.
  119. Lorand L. Acquired inhibitors of fibrin stabilization: A class of hemorrhagic disorders of diverse origins. In: Anticoagulants: Physiologic, Pathologic and Pharmacologic, Green D (Ed), CRC Press, Cleveland 1994. p.169.
  120. Tosetto A, Castaman G, Rodeghiero F. Acquired plasma factor XIII deficiencies. Haematologica 1993; 78:5.
  121. Boehlen F, Casini A, Chizzolini C, et al. Acquired factor XIII deficiency: a therapeutic challenge. Thromb Haemost 2013; 109:479.
  122. Kohler HP, Ichinose A, Seitz R, et al. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost 2011; 9:1404.
  123. Nakamura S, Kato A, Sakata Y, Aoki N. Bleeding tendency caused by IgG inhibitor to factor XIII, treated successfully by cyclophosphamide. Br J Haematol 1988; 68:313.
  124. Daly HM, Carson PJ, Smith JK. Intracerebral haemorrhage due to acquired factor XIII inhibitor--successful response to factor XIII concentrate. Blood Coagul Fibrinolysis 1991; 2:507.
  125. Tosetto A, Rodeghiero F, Gatto E, et al. An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide. Am J Hematol 1995; 48:34.
  126. Ajzner E, Schlammadinger A, Kerényi A, et al. Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency. Blood 2009; 113:723.
  127. Ichinose A, Souri M, Japanese collaborative research group on "Acquired haemorrha-philia due to factor XIII deficiency". As many as 12 cases with haemorrhagic acquired factor XIII deficiency due to its inhibitors were recently found in Japan. Thromb Haemost 2011; 105:925.