title: Cerebrovascular events in sickle cell-beta thalassemia treated with hydroxyurea: a single center prospective survey in adult Italians.
abstract: Stroke is a common cause of morbidity and mortality in sickle cell disease (SCD) and silent cerebral infarction is the most common form of neurologic injury. The frequency and risk factors for new silent cerebral infarction are incompletely understood. Moreover, no recommended treatment has been established. Although hydroxyurea (HU) is recommended for SCD, concerns remain regarding its role in the prevention of cerebrovascular events, including silent cerebral infarction. A single center population of 104 Italian patients with HbS-ß thalassemia treated with HU has been followed for a mean of 11 years. Clinical evaluation and brain imaging by Magnetic Resonance Imaging were done before and during HU treatment. During follow-up, the number of sickle cell crises (86%, 7.8 ± 6.9 vs. 1.2 ± 0.5 per year, P < 0.0001), hospitalizations (2.5 ± 2.9 vs. 0.3 ± 1.5 per year, P < 0.0001), and days in the hospital (22.4 ± 21.9 vs. 0.3±1.5 per year, P < 0.0001) decreased significantly and HbF increased from a mean of 8-20.8%. Cerebral infarcts occurred in 37.5% of patients. Among these, 6.7% had overt strokes, while 30% had new or progressive silent cerebral infarction. Stroke and silent cerebral infarction were not related to clinical hematologic or HbF response to HU. These findings suggest that in adults, HU treatment does not prevent new cerebrovascular events or the progression of existent silent cerebral infarcts in HbS-β thalassemia. A major benefit of HU is the increase in HbF; the association of high HbF and reduced cerebrovascular disease has been weak. New treatment strategies should be developed for the prevention of sickle cerebrovascular disease.
authors.affiliation: Dipartimento di Oncologia ed Ematologia, U.O.C. Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigano
authors.forename: Alice
authors.initials: A
authors.lastname: Pecoraro
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Calvaruso
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: Sonia
authors.initials: S
authors.lastname: Iannello
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000986:Antisickling Agents / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012805:Sickle Cell Trait / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications
chemical_list: D000986:Antisickling Agents; D005319:Fetal Hemoglobin; D006918:Hydroxyurea