In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia.

Søren Nygaard, Christine L Hvas, Anne-Mette Hvas, Kasper Adelborg
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Abstract

Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the in vitro effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100 × 10 9 /L to 30 to 100 × 10 9 /L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analyses of thrombin generation (Calibrated Automated Thrombogram), thrombin-antithrombin (TAT) complex levels, prothrombin fragment 1+2 (F1+2), and rotational thromboelastometry (ROTEM) were performed. Based on dose-response relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0-388) vs. 795 (98-2121) nM × min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5-20.2) versus 5.3 (2.8-7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM assay. Six patients had elevated TAT and eight patients had elevated F1 + 2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength.

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达特帕林联合阿加曲班对新发血小板减少症重症脓毒症患者的体外止血作用。
血小板减少症在危重症脓毒症患者中很常见,同时他们发生血栓栓塞事件的风险也增加。因此,选择抗凝预防的患者群体是具有挑战性的。我们研究了低分子肝素(达尔特帕林)和直接凝血酶抑制剂(阿加曲班)对脓毒症合并新发血小板减少患者血液止血的体外作用。血小板减少的定义是在纳入前24小时内血小板计数下降≥30%和/或从>100 × 109 /L下降到30 ~ 100 × 109 /L。我们包括5名健康个体和10名患者。进行凝血酶生成(校准自动血栓图)、凝血酶-抗凝血酶(TAT)复合物水平、凝血酶原片段1+2 (F1+2)和旋转血栓弹性测量(ROTEM)分析。根据对健康血液的剂量-反应关系的研究,在患者样本中加入预防性(0.25 IU/mL)和治疗性(0.75 IU/mL)的达特帕林,以及低浓度(0.25µg/mL)和高浓度(0.50µg/mL)的阿加曲班,每个样本都没有抗凝血剂。在患者中,治疗组的内源性凝血酶电位明显低于未使用抗凝剂的组[中位数(范围):29(0-388)比795 (98-2121)nM × min]。在高阿加曲班浓度的样品中,凝血酶滞后时间比未使用抗凝剂的样品更长[中位数(范围):15.5 (10.5-20.2)vs 5.3(2.8-7.3)分钟]。在ROTEM - INTEM试验中,达特帕林和阿加曲班都增加了凝血时间,但不影响最大凝块硬度。6例患者TAT升高,8例患者F1 + 2升高。综上所述,dalteparin主要影响危重脓毒症合并新发血小板减少患者凝血酶生成量,阿加曲班延迟凝块起始。两种抗凝剂均不影响凝块强度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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