Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease.
Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease.
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DOI：
10.1002/ajh.25933
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发表时间：
2020-11
影响因子：
12.8
通讯作者：
Gurkan UA
中科院分区：
文献类型：
--
作者：
Kucukal E;Man Y;Hill A;Liu S;Bode A;An R;Kadambi J;Little JA;Gurkan UA
镰状细胞病（SCD）是一种隐性遗传性血液病，表现为血液流变学异常。由于血红蛋白的β珠蛋白基因的点突变，镰状血红蛋白的聚合导致异常粘附和僵硬的红细胞（RBC）。溶血、异常RBC粘附和异常血液流变学共同损害SCD患者的内皮健康，导致累积的全身并发症。在这里，我们描述了一种微流控检测结合微粒子图像测速技术的集成在体外评估全血粘度（WBV）和红细胞粘附。我们检测了来自53名无血红蛋白病（HbAA，N = 10）、血红蛋白SC病（HbSC，N = 14）或纯合子SCD（HbSS，N = 29）个体的全血样本中微尺度流动的WBV和RBC与层粘连蛋白（LN）的粘附，平均WBV分别为4.50 cP、4.08 cP和3.73 cP。我们发现HbSC或HbSS受试者的WBV与RBC计数和红细胞压积相关。在常氧和生理低氧（SpO2为83%）试验下，WBV和RBC粘附之间存在显著的负相关性，其中HbSS受试者中较低的WBV与较高的RBC粘附LN相关。其他人已经发现低WBV与内皮活化相关。WBV改变和异常RBC粘附可能协同导致SCD的内皮损伤和累积病理生理学。这些结果表明，WBV和RBC粘附可能作为临床相关的生物标志物和终点，在评估新出现的靶向治疗和治愈性治疗SCD。
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 (SpO2 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.
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影响因子：
20.3
作者：
Bernaudin, Francoise;Socie, Gerard;Gluckman, Eliane
通讯作者：
Gluckman, Eliane
影响因子：
3.7
作者：
Bowers, Andre S.;Reid, Harvey L.;Reid, Marvin
通讯作者：
Reid, Marvin
DOI：
10.1016/j.trsl.2016.03.008
发表时间：
2016-07
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Alapan Y;Kim C;Adhikari A;Gray KE;Gurkan-Cavusoglu E;Little JA;Gurkan UA
通讯作者：
Gurkan UA
影响因子：
3.7
作者：
Connes P;Lamarre Y;Hardy-Dessources MD;Lemonne N;Waltz X;Mougenel D;Mukisi-Mukaza M;Lalanne-Mistrih ML;Tarer V;Tressières B;Etienne-Julan M;Romana M
通讯作者：
Romana M
影响因子：
2.3
作者：
Charlot, Keyne;Romana, Marc;Connes, Philippe
通讯作者：
Connes, Philippe