Inhibitors in haemophilia A: current management and open issues

Haemophilia. 2007 Dec:13 Suppl 5:52-60. doi: 10.1111/j.1365-2516.2007.01574.x.

Abstract

The incidence of inhibitors in haemophilia A is 21-33%. The development of inhibitors to factor VIII (FVIII) is one of the most serious complications in haemophilia therapy and is an important challenge in haemophilia care. The main short-term objective of the treatment of haemophilic patients with inhibitors is to control bleeding episodes, and the long-term one is to eradicate the inhibitor by means of immune tolerance induction (ITI). The choice of treatment for bleeding in inhibitor patients is dictated by the current inhibitor titre, the severity of the bleed and the previous anamnesic response to FVIII. In low responder inhibitor patients the best treatment is large doses of concentrates of FVIII to attain haemostatic levels of the factor infused. The same approach can also be considered in high responders who have a temporarily low inhibitor level and major haemorrhage. High responders patients with high inhibitors titre or with minor haemorrhage must be treated with bypassing agents, such as FEIBA (factor VIII inhibitor bypassing activity) or recombinant activated FVII (rVIIa); there is no agreement which of both agents should be chosen in the different clinical situations. Only in patients waiting to start ITI treatment the rFVIIa use is clearly recommended, in order to avoide an anamnesic responce. In case of failure with this agents, extracorporeal immunoadsortion may be considered. All haemophiliac children who develop an inhibitor should be considered for ITI. The start of ITI should be deferred until the inhibitor has declined below 10 Bethesda units/mL (BU ml(-1)) where possible. Starting the treatment when inhibitor titre is below 10 BU ml(-1) is the strongest predictor of success. However, there are many other points to clarify: recommended FVIII doses in the ITI; if the results can be affected by concomitant infections during ITI; if there are any differences using plasma derived or recombinant concentrates, even more if the plasma-derived concentrate contains large amounts von willebrand factor or not; age of starting the ITI and the delay in beginning it; if using immunosupresors can help in the treatment of patients with a bad prognosis; and when the treatment must be left in patients without a clear failure.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Blood Coagulation Factors / therapeutic use
  • Coagulants / therapeutic use
  • Factor VIII / immunology*
  • Factor VIIa / therapeutic use
  • Hemophilia A / drug therapy
  • Hemophilia A / immunology*
  • Hemophilia A / prevention & control
  • Humans
  • Immune Tolerance
  • Immunosorbent Techniques
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / blood*
  • Recombinant Proteins / therapeutic use

Substances

  • Blood Coagulation Factors
  • Coagulants
  • Immunosuppressive Agents
  • Isoantibodies
  • Recombinant Proteins
  • Factor VIII
  • recombinant FVIIa
  • anti-inhibitor coagulant complex
  • Factor VIIa