Risk Factors for Inhibitor Development in Mild and Moderate Hemophilia A: A Case-Control Study

• Published in: Blood 2009-11, Vol.114 (22), p.3184-3184
• Main Authors: Kempton, Christine L, Soucie, J. Michael, Miller, Connie H., Hooper, Craig, Escobar, Miguel A., Reding, Mark T., Cohen, Alice J., Key, Nigel S., Thompson, Arthur R., Manco-Johnson, Marilyn J., Abshire, Thomas C.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.3184.3184

Abstract 3184 Poster Board III-121 Inhibitor formation is a major complication of hemophilia A (HA). Although only 25% of new inhibitors occur in those with mild or moderate HA, they often lead to an increased frequency of bleeding with potentially devastating consequences. In contrast to severe HA, knowledge of risk factors for the development of inhibitors in those with mild and moderate hemophilia A is limited. This study was carried out to assess the role of intensive exposure to factor VIII (fVIII), in inhibitor formation in those with mild or moderate HA. A retrospective case-control design was utilized. Cases were initially identified among participants of the Universal Data Collection (UDC) surveillance system as those with mild or moderate HA (fVIII 1-40%) having a current or past inhibitor titer of > 1 BU/ml. Hemophilia severity and inhibitor titer were verified by the Hemophilia Treatment Center (HTC) and patients were eligible for enrollment if they had an inhibitor titer > 1 BU/ml on two consecutive occasions or had one inhibitor titer > 1 BU/ml followed by initiation of immune tolerance therapy. Additional cases were identified by the HTC. Control subjects had no history of inhibitor titer > 0.6 BU/ml and had previously received fVIII. Negative inhibitor status was confirmed by Nijmegen assay performed in a central laboratory. After informed consent was obtained, exposure information during the year prior to inhibitor development (cases) or the year prior to enrollment (controls) was gathered from clinical records and subject interview. The primary risk factor of interest was intensive treatment with fVIII defined as having received 6 or more consecutive days. Other risk factors investigated include: age, baseline fVIII activity, race, prior number of fVIII exposure days, vaccination within the prior year, product type and fVIII genotype. Forty-three cases and 65 controls met eligibility criteria and were enrolled at 16 HTCs. Seven cases and three controls were not included in the analysis after genotyping demonstrated mutations typically associated with severe disease, such as intron-22 inversion. The final analysis included 36 cases and 62 controls. Ten of these cases were originally identified in the UDC system. The mean baseline fVIII activity was similar between groups (p=0.73). The median age was 31 years (Inter-quartile range (IQR), 10-51 years) in cases and 27.5 years (IQR, 18-46 years) in controls (p=0.80). The distribution of subjec