Stroke Center, Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina; Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia.
Am J Hematol. 2014 Jan;89(1):47-51. doi: 10.1002/ajh.23586. Epub 2013 Nov 28.
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.
中风是镰状细胞贫血症（SCA）最致残的并发症之一。导致 SCA 中风或红细胞输注预防中风的分子机制尚不清楚。我们研究了 PRBC 输血对处于中风高危状态的 SCA 儿童的血清生物标志物的影响。分析了 80 名受试者的血清样本，包括基线、研究退出时间点和研究退出后 1 年。80 个样本中的 40 个来自随机分配至标准治疗组的受试者，40 个来自输血组。使用抗体固定珠检测法检测 BDNF、sVCAM-1、sICAM-1、MPO、组织蛋白酶-D、PDGF-AA、PDGF-AB/BB、RANTES（CCL5）、tPAI-1 和 NCAM-1 的水平。与标准治疗组相比，接受 PRBC 输血的患者的血清 sVCAM-1（2.2×106±0.8×106pg/mL 与 3.1×106±0.9×106pg/mL，P＜0.0001）、Cathepsin-D（0.5×106±0.1×106pg/mL 与 0.7×106±0.2×106pg/mL，P＜0.0001）、PDGF-AA（10556±4033pg/mL 与 14173±4631pg/mL，P=0.0008）、RANTES（0.1×106±0.07×106pg/mL 与 0.2×106±0.06×106pg/mL，P＜0.006）和 NCAM-1（0.7×106±0.2×106pg/mL 与 0.8×106±0.1×106pg/mL，P＜0.0006）水平显著降低。4 年中接受 20 次或更多次 PRBC 输血与血清 sVCAM-1（P＜0.001）、PDGF-AA（P=0.025）和 RANTES（P=0.048）水平降低有关。BDNF（P=0.025）、sVCAM-1（P=0.025）、PDGF-AA（P=0.01）、t-PAI-1（P=0.025）和 sICAM-1（P=0.022）的基线水平较低与中风无事件生存率较高相关。除了提高血红蛋白水平外，我们的结果表明，PRBC 输血对减少 SCD 中风的保护作用可能是由于血栓形成和血管重塑减少所致。
