title: Alpha Thalassemia is associated with decreased risk of abnormal transcranial Doppler ultrasonography in children with sickle cell anemia.
abstract: OBJECTIVE
  Cerebrovascular complications of sickle cell disease (SCD) are common, but the risk factors remain unclear. The multicenter Stroke Prevention Trial in Sickle Cell Anemia (STOP) provided an opportunity to examine alpha thalassemia-2 as a modifying risk factor, using abnormal transcranial Doppler ultrasonography (TCD) as a surrogate marker for cerebrovascular disease. The authors hypothesized that children with abnormal TCD are less likely to have alpha thalassemia-2, and an increased hemoglobin level accounts for this protective effect.
  
  
  METHODS
  A retrospective study was conducted of children with SCD who had both alpha gene and TCD data from STOP: 128 with TCD of at least 200 cm/s (abnormal TCD) and 172 with TCD less than 170 cm/s (normal TCD).
  
  
  RESULTS
  Alpha thalassemia-2 was more frequent in the normal TCD group compared with the abnormal TCD group. The odds ratio for normal TCD and alpha thalassemia-2 was 4.1. Adjusting for either hemoglobin level or red cell size (mean corpuscular volume) reduced the odds ratio only slightly. Age, normal TCD, and alpha thalassemia-2 had significant statistical interaction, so that alpha thalassemia-2 was not related to TCD for age 10 years or older.
  
  
  CONCLUSIONS
  The frequency of alpha thalassemia-2 was significantly higher in children with normal TCD. Speculation on mechanisms of effect includes improved erythrocyte deformability, reduced red cell adhesion, and reduced nitric oxide scavenging in alpha thalassemia-2. The association of alpha thalassemia-2 and normal TCD adds to the evidence on the protective effects of alpha thalassemia-2 in SCD and highlights the contribution of epistatic factors.
authors.affiliation: Emory University School of Medicine and Georgia Comprehensive Sickle Cell Center, Atlanta, Georgia 30303, USA.
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Hsu
authors.forename: Scott T
authors.initials: ST
authors.lastname: Miller
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wright
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kutlar
authors.forename: Virgil
authors.initials: V
authors.lastname: McKie
authors.forename: Winfred
authors.initials: W
authors.lastname: Wang
authors.forename: Charles H
authors.initials: CH
authors.lastname: Pegelow
authors.forename: Catherine
authors.initials: C
authors.lastname: Driscoll
authors.forename: Anne
authors.initials: A
authors.lastname: Hurlet
authors.forename: Gerald
authors.initials: G
authors.lastname: Woods
authors.forename: Louis
authors.initials: L
authors.lastname: Elsas
authors.forename: Stephen
authors.initials: S
authors.lastname: Embury
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D017085:alpha-Thalassemia