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 ( approximate to 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.