title: Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke.
abstract: '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.
authors.affiliation: Departments of Pediatrics and Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Dowling
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Quinn
authors.affiliation: Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ramaciotti
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Kanter
authors.affiliation: The Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: Ifeyinwa
authors.initials: I
authors.lastname: Osunkwo
authors.affiliation: Haematology, Evelina Children's Hospital, Guy's and St. Thomas NHS Trust, London, UK.
authors.forename: Baba
authors.initials: B
authors.lastname: Inusa
authors.affiliation: University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Rathi
authors.initials: R
authors.lastname: Iyer
authors.affiliation: Division of Hematology, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Kwiatkowski
authors.affiliation: Cook Children's Health Care System, Ft. Worth, TX, USA.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Pediatric Hematology/Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Rhodes
authors.affiliation: Children's Cancer and Blood Disorders Center, Children's Hospital of the King's Daughters, Norfolk, VA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Owen
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Strouse
authors.affiliation: Department of Pediatrics, Hematology/Oncology, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Panepinto
authors.affiliation: Department of Hematology Oncology, UCSF Benioff Children's Hospital, Oakland, CA, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Neumayr
authors.affiliation: Department of Pediatrics, Division of Hematology & Oncology, Wayne State University, Detroit, MI, USA.
authors.forename: Sharada
authors.initials: S
authors.lastname: Sarnaik
authors.affiliation: Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Plumb
authors.affiliation: Department of Paediatric Neurology, Evelina Children's Hospital, London, UK.
authors.forename: Nomazulu
authors.initials: N
authors.lastname: Dlamini
authors.affiliation: Developmental Neurosciences, UCL Institute of Child Health, London, UK.
authors.forename: Fenella
authors.initials: F
authors.lastname: Kirkham
authors.affiliation: Departments of Clinical Science (Biostatistics) and Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D019320:Embolism, Paradoxical / Q000209:etiology; D005260:Female; D006261:Headache / Q000209:etiology; D006343:Heart Septal Defects / Q000150:complications / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D015995:Prevalence; D012307:Risk Factors; D020521:Stroke / Q000209:etiology*; D055815:Young Adult
keywords: cardiology; clinical research; sickle cell anaemia; stroke