Elevated d-dimer predicts worse outcomes in hospitalized adults with sickle cell crisis: A real-world multicenter study

Abstract Background: Sickle cell disease (SCD) is marked by recurrent vaso-occlusive crises, which account for the majority of acute hospital encounters and contribute significantly to long-term morbidity and mortality. D-dimer, a fibrin degradation product, reflects intravascular fibrin turnover and thrombo-inflammatory activity, and may serve as a biomarker of ongoing vaso-occlusion. This study aimed to evaluate the prognostic utility of elevated D-dimer levels in hospitalized adults with SCD crisis using a large, real-world dataset. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (68 healthcare organizations). Adults aged ≥18 years hospitalized with a diagnosis of sickle cell crisis (ICD-10: D57.x with crisis modifiers) between January 1, 2000, and January 1, 2024 were included. Patients were stratified into two cohorts based on D-dimer levels: elevated (≥ 0.5 µg/mL FEU or ≥ 250 ng/mL DDU) and non-elevated (below these thresholds). Propensity score matching (1:1) was performed for demographics, comorbidities, and medication use, resulting in 636 patients in each group. Outcomes included all-cause hospitalization, blood transfusion, acute chest syndrome (ACS), venous thromboembolism (VTE), and mortality. Kaplan-Meier survival analysis was performed; hazard ratios (HR) with 95% confidence intervals (CI) and log-rank p-values were used to compare outcomes. Results: The risk of ACS was 40.6% in the elevated D-dimer group vs. 26.7% in the non-elevated group, HR 1.69 (95% CI 1.39–2.05), p<0.001. Blood transfusion occurred in 47.2% of patients with elevated D-dimer and 33.8% with non-elevated D-dimer, HR 1.52 (1.27–1.81), p<0.001. Hospitalization occurred in 88.5% of the elevated group and 79.9% of the non-elevated group, HR 1.38 (1.22–1.56), p<0.001. VTE, excluding patients with prior VTE events, occurred in 22.1% of the elevated group vs. 15.1% of the non-elevated group, HR 1.55 (1.14–2.11), p=0.005. Mortality occurred in 11.2% of patients with elevated D-dimer and 9.1% of those with normal D-dimer, HR 1.21 (0.86–1.71), p=0.280. Conclusion: In this large, multicenter cohort study of adults hospitalized with SCD, elevated D-dimer at presentation was significantly associated with higher risk of ACS, need for blood transfusion, VTE, and all-cause hospitalization. While mortality did not achieve statistical significance, the consistent trend toward worse outcomes suggests that D-dimer may serve as a clinically meaningful prognostic biomarker in sickle cell crisis. Given its widespread availability and routine use in inpatient settings, D-dimer could offer an accessible tool for early risk stratification and triage in SCD flares. Prospective studies are needed to validate these associations and evaluate its role in guiding care pathways.