Schneider D J, Tracy P B, Mann K G, Sobel B E
Department of Medicine, University of Vermont College of Medicine, Burlington 05405, USA.
Circulation. 1997 Nov 4;96(9):2877-83. doi: 10.1161/01.cir.96.9.2877.
Because activation of platelets and of the coagulation system are interdependent mediators of thrombosis, platelet activation was characterized in whole blood in the presence of anticoagulants used to assess platelet function in vitro or as treatment for patients with occlusive arterial disease.
Blood was anticoagulated alone or in combination with citrate, ethylenediaminetetraacetatic acid, corn trypsin inhibitor (CTI, an inhibitor of activated factor XII), heparin, enoxaparin, recombinant tick anticoagulant peptide (rTAP), or recombinant hirudin. Platelet activation in response to adenosine diphosphate (ADP) or collagen was detected by assay of P-selectin on the platelet surface delineated by flow cytometry. Although minimal activation was seen without ADP, the fraction of platelets expressing P-selectin in response to ADP was greatest in blood anticoagulated with citrate compared with CTI and all other anticoagulants. ADP-induced platelet activation was greater in blood anticoagulated with heparin compared with an equipotent anti-Xa concentration of enoxaparin. More variable results were seen with collagen, but platelet activation in the presence of citrate was greater than that with CTI.
Interpretation of assays of inhibition of platelet activation by potentially therapeutic agents in vitro requires consideration of the effects of anticoagulants used. In addition, anticoagulants other than standard heparin may potentiate efficacy of antiplatelet drugs.
由于血小板活化和凝血系统活化是血栓形成的相互依存的介质，因此在用于体外评估血小板功能或作为闭塞性动脉疾病患者治疗药物的抗凝剂存在下，对全血中的血小板活化进行了表征。
血液单独抗凝或与柠檬酸盐、乙二胺四乙酸、玉米胰蛋白酶抑制剂（CTI，活化因子XII的抑制剂）、肝素、依诺肝素、重组蜱抗凝肽（rTAP）或重组水蛭素联合抗凝。通过流式细胞术检测血小板表面P-选择素的含量来检测对二磷酸腺苷（ADP）或胶原的血小板活化。虽然在没有ADP的情况下观察到最小程度的活化，但与CTI和所有其他抗凝剂相比，在柠檬酸盐抗凝的血液中，对ADP作出反应表达P-选择素的血小板比例最大。与等效抗Xa浓度的依诺肝素相比，肝素抗凝的血液中ADP诱导的血小板活化更大。胶原诱导的结果更具变异性，但柠檬酸盐存在下的血小板活化大于CTI存在下的活化。
在体外解释潜在治疗药物对血小板活化的抑制作用的检测结果时，需要考虑所用抗凝剂的影响。此外，除标准肝素外的抗凝剂可能会增强抗血小板药物的疗效。
