Background: Sickle cell disease is associated with both thrombotic and hemorrhagic complications, particularly during vaso-occlusive crises (VOC). The clinical impact of long-term anticoagulation in this setting remains unclear. This study aimed to evaluate the association between long-term anticoagulation use and inpatient outcomes in adults hospitalized for VOC using a nationally representative and weighted dataset.

Methods: We performed a weighted retrospective analysis of the National Inpatient Sample from 2016 to 2022, identifying adult hospitalizations for sickle cell VOC. Long-term anticoagulation was identified as a secondary diagnosis. Primary outcomes included inpatient mortality, length of stay (LOS), and total hospital charges. Secondary outcomes included acute chest syndrome, cerebral infarction, pulmonary embolism, deep vein thrombosis, hematuria, red blood cell (pRBC) transfusion, and bleeding events including gastrointestinal bleeding, epistaxis, hemoptysis, and intracerebral hemorrhage. National estimates were calculated using survey weights. Multivariable logistic and linear regression models were used, adjusting for demographics, hospital characteristics, comorbidities, and confounders including atrial fibrillation, prior thromboembolism, mechanical heart valves, chronic kidney disease, and cirrhosis.

Results: A total of 581,319 weighted hospitalizations for sickle cell VOC were analyzed, of which 77,229 (13.2%) involved patients on long-term anticoagulation. These patients were older (mean age 35.6 vs. 32.1 years, p<0.0001), more likely to be female (64.1% vs. 45.6%, p<0.0001), and had a higher comorbidity burden. Inpatient mortality was low overall (0.5%) and did not differ significantly between groups (0.50% with anticoagulation vs. 0.53% without, p=0.6), with an adjusted odds ratio of 0.811 (p=0.18). Mean LOS was longer in the anticoagulated group (6.34 vs. 5.41 days, p<0.0001), with an adjusted increase of 0.35 days (p<0.0001). Mean hospital charges were also higher ($49,374 vs. $43,569, p<0.0001), with an adjusted increase of $1,488.10 (p=0.09).

Pulmonary embolism occurred in 3.6% of anticoagulated patients compared to 0.9% without, and deep vein thrombosis occurred in 1.0% vs. 0.2%, respectively (both p<0.0001). Anticoagulation was associated with adjusted odds increases of 479% for pulmonary embolism and 461% for deep vein thrombosis. Epistaxis occurred in 0.9% vs. 0.5% (p<0.0001), and hemoptysis was also significantly more common. Anticoagulated patients had 9.7% lower odds of requiring pRBC transfusion (p<0.0001). No significant differences were observed in adjusted rates of acute chest syndrome, cerebral infarction, hematuria, intracerebral hemorrhage, or other hemorrhage.Conclusion: In this large, weighted national cohort, long-term anticoagulation use in patients hospitalized with sickle cell vaso-occlusive crisis was associated with a distinct complication profile: significantly higher risks of thrombotic and select bleeding events, alongside reduced need for transfusion, and no difference in inpatient mortality. These findings reflect the complex and often competing risks that characterize anticoagulation in this setting and highlight the importance of individualized, context-specific clinical judgment.

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2025
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