Sickle cell disease, sickle trait and the risk for venous thromboembolism: a systematic review and meta-analysis

Abstract

BackgroundGlobally, sickle cell disease (SCD) is one of the most common haemoglobinopathy. Considered a public health problem, it leads to vessel occlusion, blood stasis and chronic activation of the coagulation system responsible for vaso-occlussive crises and venous thromboembolism (VTE) which may be fatal. Although contemporary observational studies suggest a relationship between SCD or sickle trait (SCT) and VTE, there is lack of a summary or meta-analysis data on this possible correlation. Hence, we propose to summarize the available evidence on the association between SCD, SCT and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe searched PubMed and Scopus to identify all cross-sectional, cohort and case-control studies reporting on the association between SCD or SCT and VTE, DVT or PE in adults or children from inception to April 25, 2017. For measuring association between SCD or SCT and VTE, DVT, or PE, a meta-analysis using the random-effects method was performed to pool weighted odds ratios (OR) of risk estimates.ResultsFrom 313 records initially identified from bibliographic databases, 10 studies were eligible and therefore included the meta-analysis. SCD patients had significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6–7.5, p < 0.001), DVT (OR 1.1, 95% CI 1.1–1.2, p < 0.001) and PE (pooled OR 3.7, 95% CI 3.6–3.8, p < 0.001) as compared to non SCD-adults. A higher risk of VTE (OR 33.2, 95% CI 9.7–113.4, p < 0.001) and DVT (OR 30.7, 95% CI 1.6–578.2, p = 0.02) was found in pregnant or postpartum women with SCD as compared to their counterparts without SCD. Compared to adults with SCT, the risk of VTE was higher in adults with SCD (pooled OR 3.1, 95% CI 1.8–5.3, p < 0.001), and specifically in SCD pregnant or postpartum women (OR 20.3, 95% CI 4.1–102, p = 0.0003). The risk of PE was also higher in adults with SCD (OR 3.1, 95% CCI 1.7–5.9, p = 0.0004) as compared to those with SCT. The risk of VTE was higher in individuals with SCT compared to controls (pooled OR 1.7, 95% CI 1.3–2.2, p < 0.0001), but not in pregnant or postpartum women (OR 0.9, 95% CI 0.3–2.9, p = 0.863). Compared to controls, SCT was associated with a higher risk of PE (pooled OR 2.1, 95% CI 1.2–3.8, p = 0.012) but not of DVT (pooled OR 1.2, 95% CI 0.9–1.7, p = 0.157).ConclusionIndividuals with SCD, especially pregnant or postpartum women, might have a higher risk of VTE compared to the general population. SCT might also increases the risk of VTE. However, currently available data are not sufficient to allow a definite conclusion. Further larger studies are needed to provide a definitive conclusion on the association between SCD, SCT and VTE.Electronic supplementary materialThe online version of this article (10.1186/s12959-018-0179-z) contains supplementary material, which is available to authorized users.

Factor V Leiden and prothrombin G20210A mutations and risk of vaso-occlusive complications in sickle cell disease: A meta-analysis through the lens of nephrology

“…Coinheritance of protein-C, protein-S or antithrombin deficiency further worsens the hypercoagulable state in SCD patients (4). Further, several studies investigated the association between prothrombotic factors and the risk of venous thromboembolism in SCD patients (5,6).…”

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

“…SCD patients have a four-to 100-fold increased risk for VTE compared with the general population. [33][34][35] Many of these cohorts have relied solely on ICD coding and the risk factors for VTE in SCD patients are not clear. We applied a comprehensive approach integrating VTE events, identified by ICD coding and manually confirmed through the medical records, with clinical and laboratory variables to identify risk factors for VTE.…”

Coagulation Status and Venous Thromboembolism Risk in African Americans: A Potential Risk Factor in COVID-19

“…Sickle cell disease is an inherited blood disorder, caused by a mutation in the HBB gene, that results in production of abnormal hemoglobin and can be identified by the traditional C-shaped (sickle-shaped) red blood cells in place of the traditional round cell shape. 61 , 62 This morphologic change results in the cells having a higher likelihood of getting lodged in the microvasculature and more prone to aggregate than regular blood cells, causing blood flow obstruction and serving as a nidus for clot formation. 63 These morphological red blood cell changes along with activation of the coagulation system may result in a vaso-occlusive crisis.…”

“… 64 Individuals with SCD are at a significantly higher risk of developing DVT and PE. 61 , 62 In addition to increasing the rate of thrombus formation, the presence of the sickle shape also appears to result in a denser thrombus and the clot itself appears to be more resistant to fibrinolysis. 65 Although clinical SCD is only present in an estimated 100 000 patients in the United States, the sickle cell trait is present in up to 8% of the African American population, with SCD flagged as an important risk factor for VTE.…”