Sickle Cell Disease and Risk of Venous Thromboembolism: A Systematic Review

Abstract

Background: Sickle cell disease (SCD) is associated with a prothrombotic state, but clinical venous thromboembolism (VTE) estimates differ markedly between population-based, inpatient, paediatric, maternity and referral-care settings.

Objective: To critically synthesise evidence on deep vein thrombosis (DVT), pulmonary embolism (PE) and VTE in SCD, prioritising comparative risk and interpretable incidence; recurrence and associated clinical factors were secondary outcomes.

Methods: Primary clinical studies published between 1 January 2000 and 30 June 2025 were identified through targeted biomedical index, publisher-record and citation searching. Fifteen individually logged candidate reports were assessed; twelve original studies with clinical VTE data met the review criteria. Published denominators, effect estimates and study methods were compared narratively using PRISMA 2020 and SWiM reporting principles. Meta-analysis was not performed.

Results: Among 1,523 adolescents and adults with SCD, first-VTE incidence was 5.2 per 1,000 person-years (95% CI 3.8–6.9). A California cohort reported 696 incident cases among 6,237 patients (11.2%). Pregnancy-related VTE was recorded in 720/6,388 people with SCD (11.3%) versus 202/17,110 controls (1.2%; reported OR 10.6, 95% CI 9.1–12.5). Paediatric cohorts reported 181/10,454 (1.7%) and 12/414 (2.9%) events. Greater disease severity, central venous catheters and pregnancy were recurrently associated with VTE; recurrence and mortality also carried a substantial burden.

Conclusion: The available observational evidence indicates an important VTE burden in SCD, especially in particular adult and pregnancy populations. Interpretation depends on whether the denominator is patients, hospital admissions, person-time or patients surviving a prior event. Heterogeneous designs and incomplete ascertainment of the full literature limit the precision and generalisability of any single risk estimate.