National trends and demographic disparities in mortality due to bleeding disorders in the u.S., 1999–2020

Abstract Background: Bleeding disorders encompass a diverse group of conditions, from inherited hemophilia to acquired coagulopathies like Disseminated Intravascular Coagulation (DIC). While mortality for specific disorders such as hemophilia and Immune Thrombocytopenic Purpura (ITP) has been analyzed, a comprehensive, category-wide examination of the mortality burden in the United States is absent. This gap prevents a full understanding of the shifting landscape of these conditions. Our study provides the first complete synthesis of mortality trends and disparities across the entire bleeding disorders, aiming to identify the relative public health impact of each component. Methods: We conducted a retrospective analysis of U.S. mortality data from 1999–2020 using the CDC WONDER Underlying Cause of Death database. All death certificates listing ICD-10 codes D65–D69 were included. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. standard population. Temporal trends were analyzed using Joinpoint regression to estimate annual percent change (APC) and annualized percent change. Analyses were stratified by condition, sex, age group, U.S. Census region, state, urbanization level, race, and Hispanic ethnicity. Results: Between 1999 and 2020, there were 59,320 deaths attributed to bleeding disorders. Absolute deaths rose modestly from 2,601 to 2,832 (annualized change +0.45%/year), while the AAMR declined from 1.0 to 0.7 per 100,000 (AAPC –1.68%). DIC deaths decreased by –0.43%/year, hereditary factor VIII deficiency by –0.31%/year, and purpura and other hemorrhagic conditions by –0.58%/year, whereas other coagulation defects increased from 937 to 1,380 deaths (+1.98%/year). Among specific coagulation defects, von Willebrand disease (+1.39%/year), hereditary deficiency of other clotting factors (+3.99%/year), acquired coagulation factor deficiency (+1.10%/year), other specified coagulation defects (+2.74%/year), and unspecified coagulation defects (+1.23%/year) all showed increases. Regionally, mortality rose most in the West (+1.38%/year), followed by the South (+0.75%/year) and Midwest (+0.36%/year), while the Northeast declined (–0.31%/year). State-level APC ranged from –0.9% in Alabama to >+7% in Arkansas and Delaware, with notable increases in Arizona (+3.98%), Georgia (+3.83%), and Florida (+2.30%). Urbanization analysis showed stability in large central metro areas (–0.03%/year), moderate increases in large fringe (+0.54%/year) and small metro areas (+0.71%/year), and higher increases in medium metro (+1.28%/year) and micropolitan nonmetro areas (+1.36%/year). By age, the largest increases occurred among adults aged 55–64 years (+2.83%/year) and 25–34 years (+2.63%/year), with stability in ≥85 years (+0.26%/year) and a decline in 75–84 years (–0.62%/year). Mortality increased in both sexes, with a greater rise among males (+0.88%/year) compared with females (+0.12%/year). Racial disparities were pronounced, with the highest increases in American Indian/Alaska Native (+9.36%/year) and Asian/Pacific Islander (+5.73%/year) populations, compared to smaller increases in Black (+0.61%/year) and White (+0.35%/year) individuals. Hispanic mortality rose sharply (+16.89%/year) versus a modest increase among non-Hispanics (+0.25%/year). Conclusion: The shifting mortality profile of bleeding disorders in the United States reflects a complex interplay of demographic, geographic, and clinical factors. While overall rates have declined, rising deaths in younger and middle-aged adults, increasing burden in males, disproportionate growth in Hispanic, American Indian/Alaska Native, and Asian populations, and sharp geographic variations underscore critical gaps in equitable care. These patterns highlight the need for a multipronged strategy—enhanced surveillance systems, equitable access to advanced diagnostics and therapies, targeted outreach in high-burden regions, and culturally tailored education for at-risk groups. Prioritizing research on acquired coagulopathies, particularly DIC, and ensuring that therapeutic advances reach underserved populations will be essential to curb preventable mortality and close persistent disparities.