Standardized microfluidic assessment of red blood cell-mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease.
Standardized microfluidic assessment of red blood cell-mediated microcapillary occlusion: Association with clinical phenotype and hydroxyurea responsiveness in sickle cell disease.
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红细胞介导的微毛细血管阻塞的标准化微流控评估：镰状细胞病的临床表型和羟基脲反应性
DOI：
10.1111/micc.12662
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Gurkan UA
中科院分区：
文献类型：
--
作者：
Man Y;Kucukal E;An R;Bode A;Little JA;Gurkan UA
我们提出了一个标准化的体外微流控检测和闭塞指数（OI）的红细胞（RBC）介导的微毛细血管闭塞及其临床关联的镰状细胞病（SCD）的评估。在7例血红蛋白-SC病（HbSC）受试者、18例纯合子SCD（HbSS）受试者和5例对照个体（HbAA）中评估了以OI为代表的RBC介导的微毛细血管闭塞及其临床相关性。我们根据OI分布确定了两个HbSS亚群。与HbSS和较低OI的受试者相比，具有相对较高OI的HbSS受试者的血红蛋白水平、胎儿血红蛋白（HbF）水平和平均红细胞体积（MCV）显著较低，但血清乳酸脱氢酶水平和绝对网织红细胞计数显著较高。具有相对较高OI的HbSS受试者更有可能合并诊断为肺内分流（IPS）。此外，在HbSS受试者中，OI较低与羟基脲（HU）反应性相关，如HbF水平和MCV显著升高所证明。我们证明了红细胞介导的微毛细血管阻塞和OI与SCD患者的临床表型和HU反应性相关。所提出的标准化微流控测定可用于评估SCD的临床表型和评估治疗结果，包括旨在改善RBC变形性和微循环健康的新兴靶向和治愈性治疗。
We present a standardized in vitro microfluidic assay and Occlusion Index (OI) for the assessment of red blood cell (RBC)-mediated microcapillary occlusion and its clinical associations in sickle cell disease (SCD). RBC-mediated microcapillary occlusion represented by OI and its clinical associations were assessed for 7 subjects with hemoglobin-SC disease (HbSC), 18 subjects with homozygous SCD (HbSS), and 5 control individuals (HbAA). We identified two sub-populations with HbSS based on the OI distribution. HbSS subjects with relatively higher OIs had significantly lower hemoglobin levels, lower fetal hemoglobin (HbF) levels, and lower mean corpuscular volume (MCV), but significantly higher serum lactate dehydrogenase levels and absolute reticulocyte counts, compared to subjects with HbSS and lower OIs. HbSS subjects who had relatively higher OIs were more likely to have had a concomitant diagnosis of intrapulmonary shunting (IPS). Further, lower OI associated with hydroxyurea (HU) responsiveness in subjects with HbSS, as evidenced by significantly elevated HbF levels and MCV. We demonstrated that RBC mediated microcapillary occlusion and OI associated with subject clinical phenotype and HU responsiveness in SCD. The presented standardized microfluidic assay may be useful for evaluating clinical phenotype and assessing therapeutic outcomes in SCD, including emerging targeted and curative treatments that aim to improve RBC deformability and microcirculatory health.
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DOI：
10.4084/mjhid.2017.063
发表时间：
2017-11-01
影响因子：
3.2
作者：
Adeodu, Oluwagbemiga O.;Akinlosotu, Morenike A.;Oseni, Saheed B. A.
通讯作者：
Oseni, Saheed B. A.
影响因子：
20.3
作者：
Kato, GJ;McGcwan, V;Gladwin, MT
通讯作者：
Gladwin, MT
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：
7.5
作者：
Desai, Payal C.;Brittain, Julia E.;Ataga, Kenneth I.
通讯作者：
Ataga, Kenneth I.
影响因子：
5
作者：
Diez-Silva M;Dao M;Han J;Lim CT;Suresh S
通讯作者：
Suresh S