Increased Prevalence of Potential Right-to-Left Shunting in Children with Sickle Cell Anemia and Stroke

'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12.7 +/- 4.8 years, 54.4% male) and a control group without SCA or stroke (n = 123; mean age 12.1 +/- 4.9 years, 53.3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45.6% vs. 23.6%, P < 0.001). The odds ratio for potential RLS in the SCA + stroke group was 2.7 (95% confidence interval: 1.6-4.6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23.8% vs. 5.7%, P < 0.001) but not intracardiac shunting (21.8% vs. 18.7%, P = 0.533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.