Abstract
Objective: Hematological malignancies lead to thrombosis through multifactorial mechanisms, including cytokine-mediated endothelial activation, increased tissue factor expression, chemotherapy-induced vascular damage, and impaired fibrinolysis. These factors all significantly contribute to increased thromboembolic events and related mortality. In this study, we analyzed national trends in thromboembolism-related mortality among patients with hematological cancers in the United States from 1999 through 2023 to identify temporal patterns and demographic disparities.
Methods: We extracted mortality data from the CDC WONDER Multiple Cause of Death database spanning 1999–2023. Cases involving hematologic malignancies were identified using ICD-10 codes C81–C96, while thromboembolic events were identified with ICD-10 codes I26.0–I26.9 and I82.0–I82.9. Age-Adjusted Mortality Rate (AAMR) and Crude Mortality Rate (CMR) were calculated per 1,00,000 individuals. Joinpoint regression analysis was performed to detect significant changes in annual percent change (APC) and average annual percent changes (AAPCs), with statistical significance defined as p < 0.05.Results: A total of 19,324 deaths involving thromboembolism-related mortality in hematologic malignancies were identified from 1999 to 2023. Overall AAMR remained stable through 2018 (APC: –0.25%; 95% CI: –1.07 to +0.41), followed by a sharp increase from 2018 to 2021 (APC: +19.35%; 95% CI: +11.07 to +23.70; p=0.02), and then a decline from 2021 to 2023 (APC = –8.93, 95 % CI -8.9 to -16.9).
Female patients experienced a significant increase in mortality from 2014 to 2023 (APC: +4.65%; 95% CI: +2.40 to +9.96). In males, mortality rose sharply from 2018 to 2021 (APC: +20.19%; 95% CI: –1.45 to +25.47) before declining after 2021 (APC: –6.77%; 95% CI: –16.24 to +8.66). Among racial groups, non-Hispanic Black individuals had the highest AAMR and showed a notable increase in mortality from 2015 to 2023 (APC: +6.54%; 95% CI: +3.63 to +13.58), following a prior decline from 1999 to 2015 (APC: –1.23%; 95% CI: –3.41 to +0.13). Hispanic individuals also demonstrated a reversal, with mortality rising after 2012 (APC: +6.62%; 95% CI: +3.29 to +17.42) following an earlier decline. White individuals experienced a modest increase from 2018 to 2021 (APC: +20.74%; 95% CI: –1.03 to +25.81), followed by a decline in mortality thereafter.
Our analysis of trends across U.S. census regions showed that the Midwest experienced the sharpest increase from 2018 to 2021 (APC: +23.69%; 95% CI: +14.45 to +29.20), followed by a steep decline from 2021 onwards (APC: –15.31%; 95% CI: –24.89 to –4.29). The South exhibited a sustained rise in mortality from 2015 to 2023 (APC: +7.48%; 95% CI: +4.71 to +13.45). The Northeast and West regions showed milder changes over the same period. Mortality rates increased with age and peaked in adults aged 85 and older. Most age groups initially experienced decline, followed by increasing trends after 2015. Notably, the 55–64 age group showed a significant rise in mortality from 2015 to 2023 (APC: +6.78%; 95% CI: +4.04 to +13.33).Conclusion: We observed considerable temporal variation in thromboembolism-related mortality among patients with hematologic malignancies. There was a precipitous increase in deaths from 2018 to 2021, which was likely affected by COVID-19 pandemic-induced disturbances. This was followed by a decrease in the subsequent years. These variations were not uniform across populations. The highest burden was seen in older adults, non-Hispanic Black individuals, and residents of the South and Midwest regions. These discrepancies likely reflect a combination of both clinical risk factors and systematic gaps in access to preventive care. Addressing these disparities will require improved risk stratification, increased use of thromboprophylaxis, and targeted efforts to close structural and regional healthcare gaps.
