Blood Journal
Leading the way in experimental and clinical research in hematology

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, gender and relative high systolic blood pressure

  1. Michael R. DeBaun1,*,
  2. Sharada A. Sarnaik2,
  3. Mark J. Rodeghier3,
  4. Caterina P. Minniti4,
  5. Thomas H. Howard5,
  6. Rathi V. Iyer6,
  7. Baba Inusa7,
  8. Paul T. Telfer8,
  9. Melanie Kirby-Allen9,
  10. Charles T. Quinn10,
  11. Françoise Bernaudin11,
  12. Gladstone Airewele12,
  13. Gerald M. Woods13,
  14. Julie Ann Panepinto14,
  15. Beng Fuh15,
  16. Janet K. Kwiatkowski16,
  17. Allison A. King17,
  18. Melissa M. Rhodes18,
  19. Alexis A. Thompson19,
  20. Mark E. Heiny20,
  21. Rupa C. Redding-Lallinger21,
  22. Fenella J. Kirkham22,
  23. Hernan Sabio23,
  24. Corina E. Gonzalez24,
  25. Suzanne L. Saccente25,
  26. Karen A. Kalinyak10,
  27. John J. Strouse26,
  28. Jason M. Fixler27,
  29. Mae O. Gordon28,
  30. J. Phillip Miller29,
  31. Rebecca N. Ichord30, and
  32. James F. Casella26
  1. 1 Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University, Nashville, TN, United States;
  2. 2 Department of Pediatrics, Division of Hematology/Oncology, Wayne State University, Detroit, MI, United States;
  3. 3 Rodeghier Consultants, Chicago, IL, United States;
  4. 4 National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD, United States;
  5. 5 Department of Pediatrics, Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, United States;
  6. 6 Department of Pediatrics, Division of Hematology/Oncology, University of Mississippi Medical Center, Jackson, MS, United States;
  7. 7 Paediatrics, Evelina Children's Hospital, St Thomas' Hospital NHS Trust, London, United Kingdom;
  8. 8 Department of Pediatric Hematology, The Royal London Hospital, London, United Kingdom;
  9. 9 Hospital for Sick Children, University of Toronto, Toronto, ON, Canada;
  10. 10 Department of Pediatrics, Hematology/Oncology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, United States;
  11. 11 Department Pediatrie, Hopital Intercommunal de Creteil, Creteil, France;
  12. 12 Department of Pediatrics, Hematology/Oncology, Baylor College of Medicine, Houston, TX, United States;
  13. 13 Department of Pediatrics, Hematology/Oncology, University of Missouri-Kansas City, Kansas City, MO, United States;
  14. 14 Department of Pediatrics, Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, United States;
  15. 15 Department of Pediatrics, Hematology/Oncology, Brody School of Medicine, Greenville, NC, United States;
  16. 16 Department of Pediatrics, Hematology/Oncology, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA, United States;
  17. 17 Department of Pediatrics, Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, United States;
  18. 18 Department of Pediatrics, Hematology/Oncology, Ohio State University, Columbus, OH, United States;
  19. 19 Department of Pediatrics, Hematology/Oncology, Northwestern University, Chicago, IL, United States;
  20. 20 Department of Pediatrics, Hematology/Oncology, Indiana University Purdue University Indiana, Indianapolis, IN, United States;
  21. 21 Department of Pediatrics, Hematology/Oncology, University of North Carolina at Chapel HIll, Chapell Hill, NC, United States;
  22. 22 Neurosciences Unit, Institute of Child Health (University College London), London, United Kingdom;
  23. 23 Department of Pediatrics, Hematology/Oncology, Wake Forest University Health Sciences, Winston-Salem, NC, United States;
  24. 24 Department of Pediatrics, Hematology/Oncology, Georgetown University Hosptial, Washington, DC, United States;
  25. 25 Department of Pediatrics, Hematology/Oncology, University of Arkansas Medical Sciences, Little Rock, AR, United States;
  26. 26 Department of Pediatrics, Hematology/Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;
  27. 27 Department of Pediatrics, Hematology/Oncology, Sinai Hospital, Baltimore, MD, United States;
  28. 28 Department of Ophthalmology and Visual Sciences, Biostatistics, Washington University School of Medicine, St. Louis, MO, United States;
  29. 29 Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States;
  30. 30 Department of Pediatrics, Neurology, University of Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  1. * Corresponding author; email: michael.debaun{at}vanderbilt.edu

Abstract

The most common form of neurological injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial), we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCI were diagnosed in 30.8% (251 of 814) participants who completed all evaluations, and had valid data on all pre-specified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration p < 0.001; higher baseline systolic blood pressure (SBP), p = 0.013; and male gender, p = .026; were statistically significantly associated with an increased risk of a SCI. Hemoglobin concentration and SBP are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov (NCT00072761).

  • Submitted May 9, 2011.
  • Accepted September 23, 2011.