Risk factors for inhibitor formation in haemophilia: a prevalent case-control study.
Risk factors for inhibitor formation in haemophilia: a prevalent case-control study.
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DOI：
10.1111/j.1365-2516.2009.02058.x
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Hemophilia Inhibitor Study
中科院分区：
文献类型：
--
作者：
Ragni MV;Ojeifo O;Feng J;Yan J;Hill KA;Sommer SS;Trucco MN;Brambilla DJ;Hemophilia Inhibitor Study
Inhibitor formation is a major complication of hemophilia treatment. In a prevalent case-control study, we evaluated blood product exposure, genotype, and HLA type on hemophilia 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, 7 of 20 (35.0%) vs. 1 of 57 (1.7%), p=0.001, and more commonly from inhibitor families, 7 of 20 (35.0%) vs. 0 of 57 (0%), p<0.001, and African-American, 12 of 63 (19.0%) vs. 6 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, 2 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 titers < 120 vs. ≥ 120 BU/ml, 6 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.
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