Hydroxyurea can be used in children with sickle cell disease and cerebral vasculopathy for the prevention of chronic complications? A meta-analysis

Abstract

We conducted a systematic review for evaluating the impact of hydroxyurea and chronic blood transfusion in children with sickle cell disease (SCD). A search was done in four databases from inception to 2017. Trials enrolling pediatric patients with SCD and cerebral vasculopathy with or without previous episode of stroke and that reported outcomes of occurrence of stroke and other events were included. Trained reviewers determined eligibility, risk of bias, and abstracted data. Random-effects meta-analysis was conducted. We found that the primary outcome was the occurrence of stroke. We found two trials that recruited 254 patients. No difference was found for confirmed stroke occurrence (risk difference 0.04 [95% CI: −0.03 to 0.03]) and for new-onset neurological deficit (risk difference 0.11 [95% CI: −0.00 to 0.21]). Transfusions provided a significant lower risk of vaso-occlussive crisis (risk difference 0.10 [95% CI: 0.001 to 0.20]). Finally, transfusions provided a lower risk of having high concentrations of abnormal hemoglobin S (mean difference 37.94 [95% CI: 27.55 to 48.32]). As a conclusion, transfusions plus chelation therapy might be used instead of hydroxyurea in children with SCD. There is a lack of high-quality research in the care of children with SCD, and therefore a call for action is needed.

Cerebral Vasculopathy in Children With Sickle Cell Disease in an Amazonian Population

“…The aim of the therapy is to maintain hemoglobin S <30%, as red blood cells increase the total volume of hemoglobin, consequently increasing oxygen saturation and decreasing the percentage of hemoglobin S. 1 The treatment, despite side effects such as iron overload, alloimmunization, transfusion reactions, and increased risk of thrombosis and mortality, constitutes currently the only proven strategy for secondary prevention of stroke, although it is not widely used. 1,4,24 More than 45% of patients may experience ischemic strokes despite regular transfusions. 26 Nevertheless, a systematic review showed that hydroxyurea was not superior to regular blood transfusion for reducing neurological events in children.…”

“…The review also associated regular blood transfusions with a lower risk of vaso-occlusive crises and found no difference for the occurrence of more serious adverse events when compared to hydroxyurea. 4 A Cochrane review was unable to show whether regular blood transfusion, for at least 1 year, differed in relation to the use of hydroxyurea for primary or secondary prevention of stroke in children at risk of stroke with abnormal transcranial Doppler and no vasculopathy. 27 In the present study, information regarding blood transfusions was not found in 3 patients (21.4%).…”

“…Guidelines do not recommend or prohibit the use of antithrombotics for primary or secondary prevention of stroke, but the American Heart Association recommends considering aspirin or another antithrombotic for secondary prevention of stroke, especially in children with arteriopathies. 4 There are 2 main therapies for preventing acute and chronic complications, both of which are disease modifiers, namely, continuous transfusion therapy and the use of hydroxyurea. 1…”

“…1 The sickle form of hemoglobin promotes chronic organic stress and systemic consequences that can be acute, such as acute chest syndrome, priapism, splenic sequestration, stroke; or chronic, such as avascular necrosis, liver dysfunction, pulmonary hypertension, among others, which potentially decrease life expectancy. 1 Children with sickle cell disease have a greater risk of stroke, 4 ischemic or hemorrhagic, which may be accompanied by neurologic or cognitive deficits, impairing the patient's quality of life, with poor school performance or serious sequelae. The ischemic event occurs when there is a higher rate of oxygen utilization by the brain than that provided by metabolism through cerebral blood flow and oxygen saturation, making tissue viability unsustainable.…”

Guidelines on sickle cell disease: secondary stroke prevention in children and adolescents. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular guidelines project: Associação Médica Brasileira - 2022

“…In a meta-analysis published in 2020, where only the SWiTCH trial had the necessary inclusion criteria to answer whether HU could replace monthly blood transfusions in secondary stroke prevention, the conclusion was that for children with SCA and a history of cerebrovascular abnormality, transfusions should be used together with iron chelation therapy. 37 (D) However, a Cochrane Database of Systematic Reviews meta-analysis concluded that only the SWiTCH trial is not enough to establish that the HU and phlebotomy increased the risk of stroke [RR 14.78 (95%CI 0.86 -253.66)] or mortality [Peto OR 0.98 (95%CI 0.06–15.92)], compared to pRBC transfusions and iron chelation. 38 (D)…”