Risk factors for inhibitor formation in haemophilia: a prevalent case-control study.

Published

Journal Article

Inhibitor formation is a major complication of haemophilia treatment. In a prevalent case-control study, we evaluated blood product exposure, genotype and HLA type on haemophilia A inhibitor formation. Product exposure was extracted from medical records. Genotype was determined on stored DNA samples by detection of virtually all mutations-SSCP (DOVAM-S) and subcycling PCR. HLA typing was performed by PCR amplification and exonuclease-released fluorescence. Cases experienced higher intensity factor, 455 vs. 200 U per exposure, P < 0.005, more frequent central nervous system (CNS) bleeding, seven of 20 (35.0%) vs. one of 57 (1.7%), P = 0.001 and more commonly from inhibitor families, seven of 20 (35.0%) vs. zero of 57 (0%), P < 0.001, and African-American, 12 of 63 (19.0%) vs. six of 117 (5.1%), P = 0.015. Among the latter, CNS bleeding was more commonly the initial bleed, 60% vs. 0%, P < 0.001, and survival was shorter, 14 vs. 38 yr, P = 0.025. Inhibitor formation was uncommon in those with missense mutations, two of 65 (3.1%) vs. 31 of 119 (26.0%), P = 0.008, and unrelated to factor VIII immunogenic epitope, P = 0.388, or HLA type, P > 0.100. Genotype was not associated with race. Time to immune tolerance was shorter for titres <120 vs. > or = 120 BU/mL, six vs. 16 months, P < 0.01, but unaffected by tolerizing dose regimen, P > 0.50. Inhibitor formation is associated with high intensity product exposure, CNS bleeding, African-American race and low frequency of missense mutations. The ideal time to initiate prophylaxis to reduce CNS bleeding and inhibitor formation will require prospective studies.

Full Text

Duke Authors

Cited Authors

  • Ragni, MV; Ojeifo, O; Feng, J; Yan, J; Hill, KA; Sommer, SS; Trucco, MN; Brambilla, DJ; Hemophilia Inhibitor Study,

Published Date

  • September 2009

Published In

Volume / Issue

  • 15 / 5

Start / End Page

  • 1074 - 1082

PubMed ID

  • 19563499

Pubmed Central ID

  • 19563499

Electronic International Standard Serial Number (EISSN)

  • 1365-2516

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2516.2009.02058.x

Language

  • eng

Conference Location

  • England