From the Guidelines
Maintaining hemoglobin S (HbS) levels below 30% through regular blood transfusions reduces stroke risk by approximately 90% in high-risk children with sickle cell disease. This approach is typically implemented for children identified as high-risk through transcranial Doppler ultrasonography showing elevated cerebral blood flow velocities (>200 cm/sec) 1. The transfusion regimen usually involves simple or exchange transfusions every 3-4 weeks, with a target hemoglobin of 9-11 g/dL and HbS <30% 1.
Key Considerations
- The effectiveness of this approach is based on the mechanism that reducing the proportion of sickled red blood cells improves blood flow, decreases vascular adhesion, and reduces vaso-occlusion in cerebral vessels 1.
- Chelation therapy with medications like deferasirox (Jadenu, Exjade) or deferiprone (Ferriprox) is often necessary to prevent iron overload from chronic transfusions.
- This preventive strategy has dramatically improved outcomes for children with sickle cell disease who are at high risk for stroke, though it requires commitment to regular transfusions and management of potential complications like iron overload, alloimmunization, and transfusion reactions 1.
Management and Prevention
- Transfusion therapy (target reduction of hemoglobin S, <30%) is effective for reducing stroke risk in those children at elevated risk 1.
- TCD screening for children with SCD is indicated starting at 2 years of age and continuing annually to 16 years of age 1.
- Continued transfusion, even in those whose TCD velocities revert to normal, is probably indicated 1.
From the Research
Stroke Risk Reduction in High-Risk Children
- Keeping HbS <30% has been shown to reduce stroke risk by ~90% in high-risk children, as demonstrated in a study published in the European journal of haematology 2.
- This study found that maintaining HbS below 30% through chronic transfusion was feasible and safe in children with sickle cell disease, and protected them from overt stroke.
- Another study published in the Journal of pediatric hematology/oncology found that splenectomy can help optimize hemoglobin S control in children with sickle cell anemia on chronic transfusion therapy for stroke prevention, resulting in a 39.77% mean reduction in HbS% 3.
Effects of HbS Concentration on Cerebral Blood Flow
- A study published in Stroke found that cerebral blood flow is elevated in sickle cell disease proportionate to the degree of anemia and is reduced by transfusion, and that the HbS fraction appears to exert a separate influence on the hyperemia, independent of total hemoglobin concentration 4.
- This study suggested caution in adapting modified transfusion regimens that allow higher HbS levels, as the possible consequences of the associated hyperemia over time are unknown.
Alternative Therapies for Stroke Prevention
- Hydroxyurea has been shown to increase fetal hemoglobin and improve the clinical course of sickle cell disease patients, but its efficacy and toxicity have not been thoroughly investigated, and physicians should be cautious in prescribing it for patients with sickle cell disease 5.
- A study published in the American journal of hematology found that hydroxyurea inhibits growth of burst forming unit-erythroid colonies in a dose-dependent manner, while fetal hemoglobin levels were increased, and that the level of S phase erythroid progenitors was similar for all groups, and BFU-E colony growth was inhibited 92-94% for all samples in a dose-dependent manner 6.