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Semin Thromb Hemost 2009; 35(8): 723-734
DOI: 10.1055/s-0029-1245105
© Thieme Medical Publishers

The Multifactorial Etiology of Inhibitor Development in Hemophilia: Genetics and Environment

Samantha C. Gouw1 , H. Marÿke van den Berg2 , 3
  • 1Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands
  • 2Department of Laboratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
  • 3Meander Medical Center, Amersfoort, The Netherlands
Further Information

Publication History

Publication Date:
18 February 2010 (online)

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ABSTRACT

The most important complication in the treatment of hemophilia A patients today is the development of inhibitory antibodies against infused factor VIII (FVIII). Inhibitor development is caused by a complex interplay between both genetic and environmental factors. The risk of developing inhibitors is greatest in previously untreated patients with severe hemophilia A. Several genetic factors, such as a positive family history of inhibitors, ethnicity, FVIII genotype, and certain polymorphisms in immune modulatory genes, are associated with the risk of inhibitor development. Treatment-related factors, such as intensive treatment with FVIII for bleeds or surgery, are associated with a higher inhibitor risk. However, regular prophylaxis seems to have a protective effect on inhibitor development. Knowledge about the risk factors of inhibitor development is a condition for predicting and in the future possibly even preventing the development of inhibitors in patients with severe hemophilia A. This review summarizes the current knowledge on the potential risk factors of inhibitor development. At present, many uncertainties still remain that will require collaborative investigation.

KEYWORDS

Factor VIII inhibitors - risk factors - prophylaxis - genetic polymorphisms - factor VIII mutation - intensive treatment

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Samantha C GouwM.D. 

Department of Pediatrics, University Medical Center Utrecht

PO Box 85090, 3508 AB Utrecht, The Netherlands

Email: s.c.gouw@umcutrecht.nl