Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease

Abstract

Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ⁰-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ⁰-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ⁰ genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.