Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia
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BACKGROUND: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS: A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS: Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
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In the SIT trial, without transfusion, silent cerebral infarct burden at baseline predicts further accrual of ischemic lesions and stroke.
“the Silent Infarct Transfusion (SIT) trial has shown that, without transfusion, SCI burden at baseline predicts further accrual of ischemic lesions and stroke (172)”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [172]
The Results (Neurologic Outcomes; page unavailable) report new or enlarged infarcts and strokes in the observation group, supporting recurrence without transfusion. But the reported baseline factors associated with recurrence are younger age, recurring headaches, and higher reticulocyte count; the paper does not report that baseline silent cerebral infarct burden predicts those outcomes. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn children with sickle cell disease, the SIT trial showed that transfusion may reduce incident silent cerebral infarcts, although SCIs were part of a composite endpoint including stroke, hampering analysis of the effect on SCI alone.
“In children with SCD, the SIT trial has shown that transfusion may reduce incident SCI, although SCIs were part of a composite endpoint that also included stroke, thus hampering the analysis of the effect of transfusion on SCI alone (172).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [172]
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- Authors
- DeBaun, M. R., Gordon, M., McKinstry, R. C., Noetzel, M. J., White, D. A., Sarnaik, S. A., Meier, E. R., Howard, T. H., Majumdar, S., Inusa, B. P. D., Telfer, P. T., Kirby-Allen, M., McCavit, T. L., Kamdem, A., Airewele, G., Woods, G. M., Berman, B., Panepinto, J. A., Fuh, B. R., Kwiatkowski, J. L., King, A. A., Fixler, J. M., Rhodes, M. M., Thompson, A. A., Heiny, M. E., Redding-Lallinger, R. C., Kirkham, F. J., Dixon, N., Gonzalez, C. E., Kalinyak, K. A., Quinn, C. T., Strouse, J. J., Miller, J. P., Lehmann, H., Kraut, M. A., Ball, W. S., Hirtz, D., & Casella, J. F.
- Affiliations
- Children's National (US)
- Wayne State University (US)
- University of Alabama at Birmingham (US)
- University of Mississippi Medical Center (US)
- St Thomas' Hospital (GB)
- Barts Health NHS Trust (GB)
- University of Toronto (CA)
- The University of Texas Southwestern Medical Center (US)
- Hôpital Intercommunal de Créteil (FR)
- Baylor College of Medicine (US)
- University of Missouri–Kansas City (US)
- Case Western Reserve University (US)
- Cincinnati Children's Hospital Medical Center (US)
- Children's Hospital of Philadelphia (US)
- Sinai Hospital (US)
- The Ohio State University (US)
- Northwestern University (US)
- Indiana University – Purdue University Indianapolis (US)
- University College London (GB)
- Georgetown University Medical Center (US)
- Washington University in St. Louis (US)
- Johns Hopkins University (US)
- National Institutes of Health (US)
- ORCID
- DeBaun, Michael R.
- Gordon, Mae
- McKinstry, Robert C.
- Meier, Emily R.
- Majumdar, Suvankar
- Inusa, Baba P.D.
- Telfer, Paul T.
- Kirby-Allen, Melanie
- Airewele, Gladstone
- Panepinto, Julie A.
- Fuh, Beng R.
- Kwiatkowski, Janet L.
- King, Allison A.
- Thompson, Alexis A.
- Kirkham, Fenella J.
- Gonzalez, Corina E.
- Quinn, Charles T.
- Strouse, John J.
- Miller, J. Philip
- Lehmann, Harold
- Kraut, Michael A.
- Ball, William S.
- Casella, James F.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-08-21
- Volume
- 371
- Issue
- 8
- Pages
- 699-710
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4195437
- OpenAlex
- W2095095757
- Cited by
- 545
- References
- 31
- Citations by year
- 2026: 27 · 2025: 24 · 2024: 36 · 2023: 47 · 2022: 42 · 2021: 45 · 2020: 52 · 2019: 38 · 2018: 46 · 2017: 61 · 2016: 69 · 2015: 34 · 2014: 18 · 2013: 3
- FWCI
- 30.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Eli Lilly and Company
- Children's Hospital of Philadelphia (UL1TR000003)
- Johns Hopkins University (UL1TR001079)
- Institute of Clinical and Translational Sciences (UL1TR000448)
- Shire
- National Institutes of Health (UL1TR001079, UL1TR000448, UL1TR000003)
- National Institute of Neurological Disorders and Stroke (U01NS042804)
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- sickle cell disease, silent cerebral infarction, blood transfusion, transfusion therapy, stroke prevention, pediatric patients, neurologic injury
- MeSH terms
- Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Female, Ferritins, Hemoglobin, Sickle, Humans, Intelligence, Male, Single-Blind Method, Secondary Prevention, Intention to Treat Analysis, Transfusion Reaction
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