Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.
Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Semin Thromb Hemost. 2022 Oct;48(7):850-857. doi: 10.1055/s-0042-1756304. Epub 2022 Sep 29.
Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.
危重症 COVID-19 患者表现出炎症和促凝状态，伴有较高的大血管和微血管血栓形成率。此外，肝素抵抗的发生率也很高；然而，通过药物监测进行个体化抗凝治疗尚未得到充分研究。我们分析了因 COVID-19 而在因斯布鲁克医科大学医院接受治疗的危重症患者的数据，这些患者根据抗 Xa 峰值水平接受了常规调整的低分子肝素 (LMWH) 剂量治疗，并定期进行了 ClotPro 分析（一种粘弹性止血全血检测）。在 91 名患者的 509 次抗 Xa 峰值测量中，根据给予的 LMWH 剂量，将其分为低于（<0.008 IU/mL/mg）、处于（0.008-0-012 IU/mL/mg）或高于（>0.012 IU/mL/mg）预期范围。除了组间比较外，我们还对抗 Xa 水平与 ClotPro 凝血时间（CT）之间的相关性进行了分析（84 名患者的 226 个时间点）。在大多数进行的测量中，抗 Xa 峰值水平仍低于预期范围（63.7%）。与达到或超过预期范围的患者相比，这些患者的 C 反应蛋白和 D-二聚体水平更高，但抗凝血酶水平更低。因此，在亚预期抗 Xa 范围组中，依诺肝素的剂量更高。重要的是，47 名（51.6%）患者在 ICU 住院期间在组间切换。抗 Xa 水平与 IN 测试 CT 呈弱相关，与 Russell 蝰蛇毒（RVV）测试 CT 呈中度相关。危重症 COVID-19 患者存在较高的 LMWH 抵抗率，但在 ICU 住院期间 LMWH 反应呈可变。因此，为了达到适当的靶范围，LMWH-抗 Xa 监测似乎是不可避免的。此外，我们建议在 LMWH 给药期间使用 ClotPro 的 RVV 测试来评估凝血状态，因为它与抗 Xa 水平相关性良好，但比抗 Xa 活性更全面地反映凝血级联反应。
