Venous Thromboembolism in Sickle Cell Crisis: Trends and Impact on Mortality and Length of Stay in Florida, 2020–2023
Harry A Obeng, Priscilla A Kabutey, Dennis D TsagliAbstract
Background
Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States and is a leading cause of recurrent hospitalizations due to vaso-occlusive crisis (VOC). Observational studies estimate that venous thromboembolism (VTE) occurs in 11–17% of adults with SCD, with a 5-year recurrence rate of 36.8% among those with severe disease. VTE is associated with increased mortality in SCD, yet population-level data examining its burden during crisis admissions remain limited. We aimed to estimate the prevalence and temporal trends of VTE among hospitalizations for sickle cell crisis in Florida from 2020 to 2023 and to evaluate the association of VTE with inpatient mortality and length of stay (LOS), accounting for demographic and insurance factors.
Methods
We conducted a retrospective study of inpatient admissions for sickle cell crisis using the Florida State Inpatient Database (SID) from 2020–2023. Hospitalizations were identified using ICD-10-CM codes for SCD with crisis. VTE was defined by ICD-10 codes for pulmonary embolism (I26.) or venous thrombosis (I82.) in any diagnosis position. Outcomes included hospital mortality and LOS. Covariates included age, sex, race/ethnicity, primary payer (private, Medicare, Medicaid, self-pay, no charge, other), Elixhauser comorbidity index (van Walraven weighting), and transfusion status. Temporal trends were assessed using multivariable logistic regression with year modeled categorically to account for non-linear effects during the COVID-19 era. Multivariable logistic regression evaluated associations with mortality, and quasi-Poisson regression assessed LOS. Interaction between VTE and calendar year was tested in mortality models. Adjusted odds ratios (aORs) and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were reported.
Results
A total of 46,446 hospitalizations for sickle cell crises were identified; 1,596 (3.4%) were complicated by VTE. The cohort was predominantly female (55.6%) and Black (91.2%). Among admissions with VTE, 60.7% were female. The annual prevalence of VTE remained stable from 2020 to 2023 (3.33% in 2020; 3.57% in 2022; 3.36% in 2023). Compared with 2020, there were no significant temporal changes in adjusted odds of VTE (2021: aOR 1.04, 95% CI 0.89–1.20; 2022: aOR 1.07, 95% CI 0.93–1.24; 2023: aOR 0.99, 95% CI 0.86–1.15). Patients with VTE were older (mean 34.8 vs 29.4 years, p < 0.001) and had greater comorbidity burden (mean Elixhauser index 5.1 vs 2.2, p < 0.001). Female sex was independently associated with higher odds of VTE compared with males (aOR 1.22; 95% CI 1.10–1.36). Increasing age (aOR 1.02 per year; 95% CI 1.02–1.03) and higher comorbidity burden (aOR 1.04 per point; 95% CI 1.03–1.05) were also associated with VTE. Insurance status differed significantly by VTE status (p < 0.001). Compared with private insurance, Medicare demonstrated a trend toward higher odds of VTE (aOR 1.16; 95% CI 1.00–1.36), while Medicaid was not independently associated with VTE. Admissions categorized as “No Charge” had higher adjusted odds of VTE (aOR 1.72; 95% CI 1.00–2.78). In-hospital mortality was higher among admissions with VTE (1.9% vs 0.5%, p < 0.001). In adjusted analyses, VTE was independently associated with more than twofold increased odds of mortality (aOR 2.27; 95% CI 1.45–3.43). Increasing age (aOR 1.02 per year) and greater comorbidity burden (aOR 1.16 per point) were also associated with mortality. Compared with private insurance, Medicare was associated with lower odds of mortality (aOR 0.52; 95% CI 0.36–0.77), and Medicaid showed a borderline protective association (aOR 0.65; p < 0.05). There was no significant interaction between VTE and year (p > 0.19). Length of stay was longer among admissions with VTE (median 6 vs 4 days, p < 0.001). In multivariable analysis, VTE was associated with a 72% longer hospital stay (IRR 1.72; 95% CI 1.66–1.78). Female sex (IRR 1.04; 95% CI 1.02–1.06) and higher comorbidity burden (IRR 1.02 per point; 95% CI 1.02–1.02) were also associated with prolonged LOS.
Conclusions
Among hospitalizations for sickle cell crisis in Florida from 2020–2023, VTE complicated 3.4% of admissions and was independently associated with more than double the odds of inpatient mortality and substantially prolonged hospitalization. Although VTE prevalence remained stable, its strong association with adverse outcomes underscores its clinical significance in this high-risk population. These findings highlight the need for improved inpatient risk stratification, optimized thromboprophylaxis strategies, and early recognition protocols during crisis admissions to reduce preventable mortality and healthcare utilization.