Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio.
Division of Hematology and Oncology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Am J Hematol. 2020 Nov;95(11):1246-1256. doi: 10.1002/ajh.25933. Epub 2020 Aug 10.
Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale flow in whole blood samples from 53 individuals with no hemoglobinopathies (HbAA, N = 10), hemoglobin SC disease (HbSC, N = 14), or homozygous SCD (HbSS, N = 29) with mean WBV of 4.50 cP, 4.08 cP, and 3.73 cP, respectively. We found that WBV correlated with RBC count and hematocrit in subjects with HbSC or HbSS. There was a significant inverse association between WBV and RBC adhesion under both normoxic and physiologically hypoxic (SpO of 83%) tests, in which lower WBV associated with higher RBC adhesion to LN in subjects with HbSS. Low WBV has been found by others to associate with endothelial activation. Altered WBV and abnormal RBC adhesion may synergistically contribute to the endothelial damage and cumulative pathophysiology of SCD. These findings suggest that WBV and RBC adhesion may serve as clinically relevant biomarkers and endpoints in assessing emerging targeted and curative therapies in SCD.
镰状细胞病（SCD）是一种隐性遗传血液疾病，表现为血液流变性异常。由于血红蛋白β-珠蛋白基因的点突变，导致异常聚合的镰状血红蛋白使红细胞（RBC）变得异常黏附且僵硬。溶血、异常 RBC 黏附以及异常血液流变性共同损害 SCD 患者的内皮健康，导致累积性全身并发症。在这里，我们描述了一种结合微粒子图像测速技术的微流控检测方法，用于对全血黏度（WBV）和 RBC 黏附的体外综合评估。我们检查了来自 53 名无血红蛋白病个体（HbAA，N = 10）、血红蛋白 SC 病（HbSC，N = 14）或纯合 SCD（HbSS，N = 29）的全血样本在微尺度流动中的 WBV 和 RBC 对层粘连蛋白（LN）的黏附，这些样本的平均 WBV 分别为 4.50 cP、4.08 cP 和 3.73 cP。我们发现 WBV 与 HbSC 或 HbSS 个体的 RBC 计数和血细胞比容相关。在常氧和生理低氧（SpO 为 83%）测试下，WBV 与 RBC 黏附之间存在显著的负相关，在 HbSS 个体中，较低的 WBV 与 LN 上更高的 RBC 黏附相关。其他人发现低 WBV 与内皮细胞激活有关。改变的 WBV 和异常的 RBC 黏附可能协同导致 SCD 的内皮损伤和累积病理生理学。这些发现表明，WBV 和 RBC 黏附可能作为评估 SCD 中新兴靶向和治愈疗法的临床相关生物标志物和终点。
