1. PFO and Stroke in Sickle Cell Re Dattani and Jackson

    Dear Sir, We read with great interest the case report by Dattani and Jackson detailing a case of potential cardioembolic stroke in a young man with sickle cell anemia (SCA), without significant cerebral vasculopathy but with PFO. We have conducted a controlled clinical study to determine the prevalence of potential left-to-right shunting (intracardiac or intrapulmonary) in children with SCA and overt clinical stroke using contrasted echocardiography in 147 children with SCA +overt stroke and a control group of 123 children without SCA or stroke. Right-to-left shunting was defined as any potential shunting detected by any method (conventional 2D, Doppler, or contrasted echocardiogram, with 2 contrast injections without Valsalva and 2 injections with Valsalva). We found that the prevalence of potential right-to-left shunting was significantly higher in the SCA+stroke group than in controls (45.6% vs 23.6%, p< 0.001). 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) (Dowling, et al., 2016).

    We agree with the Dattani and Jackson, that adults and children with SCA, while at high risk for stroke from SCA-specific risk factors such as sickle vasculopathy, are also at risk for stroke from the "traditional" risk factors for stroke in adults, including potentially treatable risk factors such as paradoxical embolization across a PFO (Dowling and Ikemba, 2011).

    Common SCA related conditions such as acute chest syndrome or pulmonary hypertension, as well as anemia itself, can increase right heart pressures, favoring right-to-left shunting and thus favoring paradoxical embolization. In patients without SCA, hypercoagulable states predispose to paradoxical embolization in adults with potential shunting and SCA is itself a hypercoagulable state. Studies of fat embolization syndrome in SCA also support the role of paradoxical embolization syndrome in SCA. Thus, we concur that both children and adults with SCA and stroke warrant more extensive clinical evaluation for "traditional" risk factors for stroke, particularly as they may be amenable to treatment.

    We suspect that similar mechanisms may be involved in the etiology of at least some of the "silent cerebral infarctions" that can be detected by MRI in up to 40% of children with SCA. We concur that further research is needed in this area but applaud the authors for highlighting the need for exploration of alternative etiologies for stroke in patients with SCA, and raising the clinical awareness of other potentially treatable stroke etiologies in this high risk population.

    Michael Morgan Dowling, MD, PhD, MSCS Departments of Pediatrics and Neurology & Neurotherapeutics University of Texas Southwestern Medical Center, Dallas, Texas

    Fenella J Kirkham, MD, FRCP, FRCPCH Developmental Neurosciences UCL Institute of Child Health London, UK


    Dattani A, Jackson A, The cause of the stroke: a diagnostic uncertainty. BMJ Case Rep. 2017 doi:10.1136/bcr-2016-218358.

    Dowling, M.M. & Ikemba, C.M. (2011) Intracardiac shunting and stroke in children: a systematic review. Journal of Child Neurology, 26, 72-82.

    Dowling MM, Quinn CT, Ramaciotti C, Kanter J, Osunkwo I, Inusa B, Iyer R, Kwiatkowski JL, Johnson C, Rhodes M, Owen W, Strouse JJ, Panepinto JA, Neumayr L, Sarnaik S, Plumb PA, Dlamini N, Kirkham F, Hynan LS; PFAST Investigators. Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke. Br J Haematol 2017 Jan;176(2):300-308

    Disclosures The authors were supported by the Doris Duke Charitable Foundation. They have no other disclosures and no conflicts of interest to report.

    Conflict of Interest:

    None declared

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