Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle...

Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high-risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM-1, sICAM-1, MPO, Cathepsin-D, PDGF-AA, PDGF-AB/BB, RANTES (CCL5), tPAI-1, and NCAM-1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM-1 (2.2 × 10(6) ± 0.8 × 10(6) pg/mL vs. 3.1 × 10(6) ± 0.9 × 10(6) pg/mL, P < 0.0001), Cathepsin-D (0.5 × 10(6) ± 0.1 × 10(6) pg/mL vs. 0.7 × 10(6) ± 0.2 × 10(6) pg/mL, P < 0.0001), PDGF-AA (10556 ± 4033 pg/mL vs. 14173 ± 4631 pg/mL, P = 0.0008), RANTES (0.1 × 10(6) ± 0.07 × 10(6) pg/mL vs. 0.2 × 10(6) ± 0.06 × 10(6) pg/mL, P < 0.006), and NCAM-1 (0.7 × 10(6) ± 0.2 × 10(6) pg/mL vs. 0.8 × 10(6) ± 0.1 × 10(6) pg/mL, P < 0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM-1 (P < 0.001), PDGF-AA (P = 0.025), and RANTES (P = 0.048). Low baseline level of BDNF (P = 0.025), sVCAM-1 (P = 0.025), PDGF-AA (P = 0.01), t-PAI-1 (P = 0.025) and sICAM-1 (P = 0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling.