Abstract
Ischemic stroke is one of the most devastating complications of sickle cell anemia (SCA). Previous studies have shown that intracardiac shunting including patent foramen ovale (PFO) can be a potential risk factor for stroke in children with SCA. This study investigates the association between PFO and overt ischemic stroke in the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort of 5,247 children with SCA of whom 1,414 had at least one clinical non-contrast transthoracic echocardiogram. Presence of PFO was taken from the clinical report. Further, we assessed the association between PFO and other clinical and hemolytic factors in children with SCA such as history of abnormal sickle stroke screen [elevated Transcranial Doppler ultrasound (TCD) velocity] and patient's baseline hemoglobin. In 642 children for whom all data were available, the adjusted odds ratio (OR) for overt stroke was higher in those with PFO but this was not statistically significant (OR: 1.49, 95% CI: 0.20–11.03, p = 0.6994). With an OR of 0.85, the study suggested less PFOs in those with abnormal TCD, but this was not statistically significant (95% CI: 0.17–4.25, p = 0.8463). Overall, the prevalence of PFO in this large sub study of non-contrast echocardiography amongst children with SCA is much lower than previous smaller studies using bubble contrast echocardiography. Overt stroke was non-statistically more common in children with SCA and PFO, but there was no evidence that PFO was more common in those with abnormal TCD, the most important pediatric sickle stroke screen.
Highlights
Sickle cell anemia (SCA) is the leading cause of overt ischemic stroke in children [1], with a stroke risk up to 10% per year without any primary stroke prevention strategy applied [2,3,4,5]
All children had at least one documented echocardiogram entered in the DISPLACE database, one clinical assessment result and one complete blood count laboratory result
We found no increased risk of stroke or abnormal Transcranial Doppler ultrasound (TCD) among those with patent foramen ovale (PFO) compared to those without PFO in children with SCA
Summary
Sickle cell anemia (SCA) is the leading cause of overt ischemic stroke in children [1], with a stroke risk up to 10% per year without any primary stroke prevention strategy applied [2,3,4,5]. Previous studies have shown patent foramen ovale (PFO) to be a significant risk factor for overt ischemic stroke in adults (without SCA) with a prevalence of up to 40% in young adults [7, 8]. In SCA, the chronic anemia and pulmonary arterial hypertension may lead to increased right heart pressure thereby predisposing to right to left shunting and paradoxical embolization; this may predispose children with SCA who have a PFO to increased risk for stroke [16]. Previous studies have shown that potential rightto-left shunting through the heart or the lungs, diagnosed with bubble contrast transthoracic echocardiograms, can be a risk factor for stroke in children with SCA [17, 18]. Because of the perceived risks of bubble contrast in children with SCA without stroke, most of these studies were limited by their small sample size and the use of control groups of children without SCA [17]
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