Regular transfusion lowers plasma free hemoglobin in children with sickle-cell disease at risk for stroke

BACKGROUND AND PURPOSE - Intravascular hemolysis releases large amounts of free hemoglobin (PFH) in plasma of sickle- cell disease (SCD) patients. PFH has been associated with harmful endothelial actions including scavenging nitric oxide (NO). Whether PFH plays a role in stroke in SCD has not been examined. METHODS - Serum levels of PFH, lactate dehydrogenase, and total bilirubin were measured in stored sera from children at risk for stroke treated in a randomized controlled trial of regular red cell transfusion (STOP study). Baseline and post-treatment (≈1 year of transfusion) were compared to determine whether treatment (which reduces stroke risk by 90%) was associated with reduction in markers of hemolysis. RESULTS - Baseline serum PFH values did not differ between treatment groups. PFH declined with repeated transfusion from 78.7±8.2 mg/dL to 34.4±3.4 mg/dL (P<0.001). With only episodic or no transfusion the drop was smaller: 80.9±7.5 to 62.8±5.0 (P=0.019). The decrease was larger in those with regular transfusion (56% versus 22%; P<0.001). Reduction of lactate dehydrogenase and total bilirubin was observed only in those on regular transfusion. CONCLUSIONS - Regular transfusion which lowers stroke risk is associated with a significant reduction in PFH. A role for PFH in promoting stroke in SCD should be investigated.