首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Effects of the new glycopeptide antibiotic teicoplanin on platelet function and blood coagulation.
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Effects of the new glycopeptide antibiotic teicoplanin on platelet function and blood coagulation.

机译:新型糖肽抗生素替考拉宁对血小板功能和凝血的影响。

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摘要

Teicoplanin, a new glycopeptide antibiotic, is structurally related to ristocetin, an antibiotic known to induce human platelet agglutination and, thus, thrombocytopenia and thromboembolic side effects. The aim of this study was to evaluate the effects of teicoplanin on platelet function in vitro and ex vivo and on blood coagulation ex vivo. In the in vitro studies, spontaneous platelet aggregation; platelet aggregation induced by ADP, collagen, and ristocetin; and the release of beta-thromboglobulin from platelets were assessed. Platelets from healthy subjects were incubated with teicoplanin at final concentrations of 100, 1,500, 5,000, and 10,000 micrograms/ml. The maximal achievable concentration with therapeutic doses is 100 micrograms/ml. When compared with saline, teicoplanin at concentrations of 100 and 1,500 micrograms/ml had no effect on platelet function, but at concentrations of 5,000 and 10,000 micrograms/ml, it induced greater spontaneous platelet aggregation (P less than 0.01) and inhibited platelet aggregation induced by ADP, collagen, and ristocetin (P less than 0.01). Teicoplanin at concentrations of 100, 1,500, and 5,000 micrograms/ml did not induce the release of beta-thromboglobulin, in contrast to teicoplanin at a concentration of 10,000 micrograms/ml and ristocetin at a concentration of 1.5 mg/ml (P less than 0.01). In the ex vivo studies, platelet count, bleeding time, plasma beta-thromboglobulin, platelet aggregation induced by ADP, ristocetin, and epinephrine, activated partial thromboplastin time, prothrombin time, thrombin clotting time, and serum fibrinogen degradation products were evaluated at days 0, 3, and 6 and at 72 h after the end of therapy. All subjects completed the study without evidence of side effects. When compared with the pretreatment values, none of the values from these assays showed a significant change at any time during and after treatment. We concluded that platelet function and blood coagulation are not affected by therapeutic concentrations of teicoplanin and that in vitro platelet function is affected only by concentrations of teicoplanin far in excess of those that are clinically achievable.
机译:Teicoplanin是一种新的糖肽抗生素,在结构上与瑞斯汀(ristocetin)相关,瑞斯汀是一种已知会诱导人血小板凝集并因此引起血小板减少和血栓栓塞性副作用的抗生素。这项研究的目的是评估替考拉宁对体外和离体血小板功能以及离体血液凝固的影响。在体外研究中,自发性血小板聚集。 ADP,胶原蛋白和瑞斯托菌素诱导的血小板凝集;并评估了血小板中β-凝血球蛋白的释放。将健康受试者的血小板与替考拉宁终浓度分别为100、1,500、5,000和10,000微克/ ml孵育。治疗剂量可达到的最大浓度为100微克/毫升。与盐水相比,替考拉宁在100和1,500微克/毫升的浓度下对血小板功能没有影响,但是在5,000和10,000微克/毫升的浓度下,它诱导更大的自发性血小板凝集(P小于0.01)并抑制诱导的血小板凝集通过ADP,胶原蛋白和瑞斯托菌素(P小于0.01)测定。与浓度为10,000微克/毫升的替考拉宁和浓度为1.5毫克/毫升的瑞斯托菌素为1.5毫克/毫升时的替考拉宁相比,浓度为100、1,500和5,000微克/毫升的替考拉宁不会诱导释放β-血栓球蛋白(P小于0.01 )。在离体研究中,在第0天评估了血小板计数,出血时间,血浆β-凝血球蛋白,ADP,瑞斯托菌素和肾上腺素诱导的血小板凝集,活化的部分凝血活酶时间,凝血酶原时间,凝血酶凝血时间和血清纤维蛋白原降解产物。 ,3和6,以及治疗结束后72小时。所有受试者均完成了研究,没有副作用的证据。当与预处理值进行比较时,这些测定的值在治疗期间和之后的任何时间都没有显示出明显的变化。我们得出的结论是,替考拉宁的治疗浓度不会影响血小板功能和凝血功能,而替考拉宁的浓度仅会远远超过临床上可达到的浓度,从而影响体外血小板功能。

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