INCT de Sangue, Haematology and Haemotherapy Centre, School of Medicine, University of Campinas - UNICAMP, Campinas, Sao Paulo, Brazil.
Clin Biochem. 2013 Dec;46(18):1798-803. doi: 10.1016/j.clinbiochem.2013.09.011. Epub 2013 Sep 21.
Intravascular hemolysis may have important pathophysiological consequences, such as the induction of cellular adhesion and vasculopathy. We compared the adhesive properties of red cells (RBC) and platelets in hereditary spherocytosis (HS), paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD) patients.
The adhesion of RBC and platelets, from patients and healthy subjects, was determined using static adhesion assays. RBC surface markers were characterized by flow cytometry and lactate dehydrogenase (LDH), plasma hemoglobin (pHb) and TNF-α were assayed in serum/plasma samples.
pHb levels were elevated in all three hemolytic diseases, indicating the incidence of intravascular hemolysis. RBC adhesion and TNF-α were augmented in HS and SCD, but not in PNH. Reticulocyte counts were raised in the three diseases, but were higher in HS and SCD than in PNH; high expressions of CD71, CD36 and CD49d were observed on SCD RBC, while CD71 alone was increased on HS and PNH RBC. Splenectomy was associated with reversals of increased pHb, RBC adhesion, reticulocytes, RBC marker expression and inflammation in HS. In contrast, platelet adhesion was elevated in SCD and PNH, but not HS. Platelet adhesion correlated significantly with serum LDH, but not pHb, in the hemolytic disease cohort; interestingly, LDH did not correlate with reticulocytes or pHb levels.
Results indicate that extravascular, rather than intravascular, hemolysis (and ensuing RBC production) may contribute to elevations in RBC adhesive properties in HS and SCD, while mechanisms peculiar to each disease may augment platelet adhesion in SCD and PNH.
血管内溶血可能具有重要的病理生理后果，如诱导细胞黏附和血管病变。我们比较了遗传性球形红细胞增多症（HS）、阵发性睡眠性血红蛋白尿症（PNH）和镰状细胞病（SCD）患者的红细胞（RBC）和血小板的黏附特性。
使用静态黏附测定法测定 RBC 和血小板的黏附。通过流式细胞术对 RBC 表面标志物进行特征分析，并测定血清/血浆样本中的乳酸脱氢酶（LDH）、血浆血红蛋白（pHb）和 TNF-α。
所有三种溶血性疾病的 pHb 水平均升高，表明存在血管内溶血。HS 和 SCD 中 RBC 黏附和 TNF-α均增加，但 PNH 中没有。三种疾病的网织红细胞计数均升高，但 HS 和 SCD 高于 PNH；SCD RBC 高表达 CD71、CD36 和 CD49d，而 HS 和 PNH RBC 仅高表达 CD71。脾切除术与 HS 中升高的 pHb、RBC 黏附、网织红细胞、RBC 标志物表达和炎症的逆转相关。相比之下，SCD 和 PNH 中血小板黏附增加，但 HS 中没有。血小板黏附与溶血疾病队列中的血清 LDH 显著相关，但与 pHb 无关；有趣的是，LDH 与网织红细胞或 pHb 水平无关。
结果表明，HS 和 SCD 中 RBC 黏附特性的升高可能是由于血管外而非血管内溶血（以及随之而来的 RBC 生成）所致，而每种疾病特有的机制可能会增加 SCD 和 PNH 中的血小板黏附。
