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. 2020 Oct 13;4(19):4739-4747.
doi: 10.1182/bloodadvances.2020002626.

Inhibitors and mortality in persons with nonsevere hemophilia A in the United States

Ming Y Lim  1 , Dunlei Cheng  2 , Michael Recht  2   3 , Christine L Kempton  4 , Nigel S Key  5
Affiliations

Inhibitors and mortality in persons with nonsevere hemophilia A in the United States

Ming Y Lim et al. Blood Adv. .

Abstract

Although persons with nonsevere hemophilia A (NSHA) account for about one-half of the hemophilia A population, epidemiological data in this subset of individuals are scarce. We set out to describe the clinical characteristics of persons with NSHA with inhibitors, and to determine mortality rates, predictors of mortality, and primary causes of death in persons with NSHA in the United States over a 9-year period (2010-2018). We queried the American Thrombosis and Hemostasis Network dataset (ATHNdataset) for information on demographics, inhibitor status, and date and cause of death. A total of 6624 persons with NSHA (86.0% men; 14.0% women) were observed for an average of 8.5 years; total 56 119 person-years . The prevalence of inhibitors was 2.6% (n = 171), occurring at a median age of 13 years. At the end of follow-up, 136 persons died at a median age of 63 years; an age-adjusted mortality rate of 3.3 deaths per 1000 person-years. Three deaths occurred in inhibitor participants. Presence of inhibitors was not associated with increased mortality risk (hazard ratio [HR], 0.7, 95% confidence interval [CI], 0.2-2.3). Factors independently associated with increased risk of death (HR, 95% CI) were the following: age (10-year increase) (2.1, 2.0-2.4); male (2.6, 1.0-6.4); hepatitis C (2.2, 1.5-3.1); and HIV (3.6, 2.2-6.0). The most common primary cause of death was malignancy (n = 27, 20.0%). In persons with NSHA, the development of inhibitors occurred at an early age and was not associated with increased mortality.

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Conflict of interest statement

Conflict-of-interest disclosure: M.R. has acted as a paid consultant to Bioverativ/Sanofi, CSL Behring, Genentech, Kedrion, NovoNordisk, Pfizer, Shire/Takeda, and uniQure; in addition, his organization has received research support from Bioverativ/Sanofi, BioMarin, Genentech, NovoNordisk, Shire/Takeda, Spark Therapeutics, and uniQure; is on the Board of Directors of Foundation for Women and Girls with Blood Disorders and Partners in Bleeding Disorders; and is employed by the American Thrombosis and Hemostasis Network. C.L.K. received honoraria for participation in advisory boards with Spark Therapeutics, Pfizer, and Genentech and research support from Novo Nordisk. N.S.K. has received research funding from Takeda, Grifols, and Pfizer; in addition, he is on a steering committee for clinical trials for uniQure and grants review committee for NovoNordisk. The remaining authors declare no competing financial interests.

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