Acquired haemophilia

Acquired haemophilia A (AHA) is a rare but potentially life-threatening bleeding disorder characterized by autoantibodies directed against coagulation factor VIII. These autoantibodies constitute the most common spontaneous inhibitor to any coagulation factor and may induce spontaneous bleeding in patients with no previous history of a bleeding disorder.[1]

Its incidence is approximately 1.5 cases/million/year.[2] The distribution is bimodal with a first period occurrence between 20 and 30 years old, which mainly corresponds to women who develop this disorder in the postpartum, and a second peak between 68 and 80 years old, corresponding to the majority of patients, with no sex difference.[3]

An underlying medical condition can be identified in up to 50% of patients, including cancer either solid or hematologic; autoimmune diseases such as rheumatoid arthritis, Sjögren syndrome, or bullous pemphigoid; administration of drugs and pregnancy. However, AHA can also emerge in elderly people without any risk factors.[4][5][6]

Overall mortality rate in AHA is varies from 20% to 70% depending on the series, attributed to the underlying disorder in about 50% of the cases, infections (5-15%) and major bleeding episodes (4%)[7][8][9]

The reason for this loss of tolerance to self-factors is still unclear. There may be different involved mechanisms, such as the presence of certain gene polymorphisms (e.g., HLA, CTLA4) and/or autoreactive CD4+ T lymphocytes.[10][11]

  1. ^ Hunth-Kühne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Lévesque H, et al. International recommendations on the diagnosis and treatment of pacients with acquired hemophilia A. Haematologica. 2009; 94: 566-75.
  2. ^ Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, 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;109:1870-7.
  3. ^ Franchini M, Vaglio S, Marano G, Mengoli C, Gentili S, Pupella S, et al. Acquired hemophilia A: a review of recent data and new therapeutic options. Hematology. 2017; 22: 514-20.
  4. ^ Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost 1981;45:200-3.
  5. ^ Morrison AE, Ludlam CA, Kessler C. Use of porcine factor VIII in the treatment of patients with acquired hemophilia.Blood 1993;81:1513-20.
  6. ^ Franchini M, Gandini G, Di Paolantonio T, Mariani G. Acquired hemophilia A: a concise review. Am J Hematol 2005;80:55-63.
  7. ^ Knoelb P, Marco P, Baudo F, Collins P, Huth-Kuhne A, Nemes L, et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012; 10: 622-31.
  8. ^ Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009; 20: 517-23.
  9. ^ Delgado J, Jiménez-Yuste V, Hernández-Navarro F, Villar A. Acquired haemophilia: review and meta analysis focused on therapy and prognostic factors. Br J Haematol. 2003; 121: 21-35.
  10. ^ Pavlova A, Zeitler H, Scharrer I, et al. HLA genotype in patients with acquired haemophilia A. Haemophilia 2010; 16:107.
  11. ^ Wootla B, Desirazu N, Friboulet A, Uda T, Lacroix-Desmazes S, Kaveri S. Varied immune response to FVIII: presence of proteolytic antibodies directed to factor VIII in different human pathologies. Clinic Rev Allerg Immunol. 2009; 37: 97-104.