Nygaard Søren, Hvas Christine L, Hvas Anne-Mette, Adelborg Kasper
Department of Clinical Biochemistry, Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
TH Open. 2023 Jan 30;7(1):e42-e55. doi: 10.1055/a-2000-6576. eCollection 2023 Jan.
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 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 /L to 30 to 100 × 10 /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.
血小板减少症在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，为这一患者群体选择抗凝预防措施具有挑战性。我们研究了低分子量肝素（达肝素）和直接凝血酶抑制剂（阿加曲班）对新发血小板减少症的脓毒症患者血液止血功能的影响。血小板减少症定义为入选前24小时内血小板计数下降≥30%和/或从>100×10⁹/L降至30至100×10⁹/L。我们纳入了5名健康个体和10名患者。进行了凝血酶生成分析（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）以及旋转血栓弹力图（ROTEM）分析。基于在健康血液中研究的剂量 - 反应关系，在患者样本中加入预防性（0.25 IU/mL）和治疗性（0.75 IU/mL）的达肝素以及低浓度（0.25 μg/mL）和高浓度（0.50 μg/mL）的阿加曲班，每个样本均设一个未加抗凝剂的对照。在患者中，治疗性达肝素样本中的内源性凝血酶潜力明显低于未加抗凝剂的样本[中位数（范围）：29（0 - 388）对795（98 - 2121）nM·min]。在高浓度阿加曲班样本中，凝血酶延迟时间长于未加抗凝剂的样本[中位数（范围）：15.5（10.5 - 20.2）对5.3（2.8 - 7.3）min]。在ROTEM INTEM分析中，达肝素和阿加曲班均延长了凝血时间，但不影响最大血凝块硬度。6名患者的TAT升高，8名患者的F1 + 2升高。总之，在新发血小板减少症的重症脓毒症患者中，达肝素主要影响凝血酶生成量，阿加曲班延迟凝血启动。两种抗凝剂均不影响血凝块强度。
