Milburn James A, Cassar Kevin, Ford Isobel, Fluck Nicholas, Brittenden Julie
Department of Vascular Surgery, University of Aberdeen and Aberdeen Royal Infirmary, Aberdeen, Scotland, UK.
Int J Artif Organs. 2011 Mar;34(3):280-7. doi: 10.5301/ijao.2011.6469.
Patients on hemodialysis (HD) have an increased risk of thrombotic events, including myocardial infarction and vascular access thrombosis. The study hypothesis is that a single session of dialysis leads to platelet, endothelial and coagulation activation. Our aim is to determine the effect of a single HD session on prothrombotic vascular biomarkers before and after a single session of hemodialysis.
Blood samples were taken from the vascular access of 55 patients immediately before and after a hemodialysis session. Platelet function was assessed by (1) flow cytometric measurement of P-selectin expression and fibrinogen binding +/- ADP stimulation, (2) Ultegra rapid platelet function assay (RPFA) using the agonists thrombin receptor activating peptide (TRAP) and arachidonic acid (AA), (3) soluble P-selectin, and (4) soluble CD40L. Coagulation (thrombin-antithrombin III [TAT] and D-dimer), endothelial von Willebrand factor (vWF) and high sensitivity C-Reactive protein (hsCRP) were assessed by ELISA.
Unfractionated heparin was given to all patients during dialysis and 30 patients (55%) were on antiplatelet agents. Post-hemodialysis there were significant increases in unstimulated platelet P-selectin (p=.037), stimulated P-selectin (p<.001), soluble P-selectin (p<.001) and soluble CD40L (p=.036). Stimulated platelet fibrinogen binding was increased post-hemodialysis (p<.001) but unstimulated fibrinogen binding was unchanged. TRAP- (p<.001] and AA-(p=.009) stimulated aggregation were reduced post-hemodialysis. There were increases post-hemodialysis in TAT (p<.001), D-dimer (p<.001), vWF (p<.001) and hsCRP (p=.011).
This study has shown that despite heparin therapy, a single session of HD induced increases in platelet, endothelial, and coagulation activation. More effective medical strategies to reduce the prothrombotic state of patients on hemodialysis should be investigated.
接受血液透析（HD）的患者发生血栓事件（包括心肌梗死和血管通路血栓形成）的风险增加。本研究假设是单次透析会导致血小板、内皮细胞和凝血激活。我们的目的是确定单次血液透析前后对血栓前血管生物标志物的影响。
在55例患者进行血液透析前后，立即从血管通路采集血样。通过以下方法评估血小板功能：（1）流式细胞术测量P-选择素表达和纤维蛋白原结合（±ADP刺激）；（2）使用凝血酶受体激活肽（TRAP）和花生四烯酸（AA）作为激动剂的Ultegra快速血小板功能测定（RPFA）；（3）可溶性P-选择素；（4）可溶性CD40L。通过酶联免疫吸附测定（ELISA）评估凝血指标（凝血酶-抗凝血酶III [TAT]和D-二聚体）、内皮血管性血友病因子（vWF）和高敏C反应蛋白（hsCRP）。
所有患者在透析期间均给予普通肝素，30例患者（55%）服用抗血小板药物。血液透析后，未刺激的血小板P-选择素（p = 0.037）、刺激后的P-选择素（p < 0.001）、可溶性P-选择素（p < 0.001）和可溶性CD40L（p = 0.036）均显著增加。血液透析后，刺激后的血小板纤维蛋白原结合增加（p < 0.001），但未刺激的纤维蛋白原结合未改变。血液透析后，TRAP刺激的聚集（p < 0.001）和AA刺激的聚集（p = 0.009）减少。血液透析后，TAT（p < 0.001）、D-二聚体（p < 0.001）、vWF（p < 0.001）和hsCRP（p = 0.011）均增加。
本研究表明，尽管进行了肝素治疗，但单次血液透析仍会导致血小板、内皮细胞和凝血激活增加。应研究更有效的医学策略以降低血液透析患者的血栓前状态。
