Journal of Blood Medicine (Apr 2024)
Risk of Intracranial Hemorrhage in Persons with Hemophilia A in the United States: Real-World Retrospective Cohort Study Using the ATHNdataset
Abstract
Jianzhong Hu,1 Martin Chandler,1 Christopher Matthew Manuel,1 Jorge Caicedo,2 Michael Denne,2 Bruce Ewenstein,2 Ali G Mokdad,2 Shan Xing,3 Michael Recht1,4,5 1American Thrombosis and Hemostasis Network, Rochester, NY, USA; 2Rare Diseases and Hematology, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 3US Value and Evidence Generation, Takeda Pharmaceuticals, U.S.A., Inc, Lexington, MA, USA; 4Yale Center for Bleeding and Clotting Disorders, Yale University School of Medicine, New Haven, CT, USA; 5National Bleeding Disorders Foundation, New York, NY, USACorrespondence: Michael Recht, National Bleeding Disorders Foundation, 7 Penn Plaza, New York, NY, 10001, USA, Tel +1 800-360-2846, Email [email protected]: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape.Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses).Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses.Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings.Keywords: bleeding, factor VIII, health insurance, hematologic disease, prophylaxis, risk factors
