Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Semin Thromb Hemost. 2022 Feb;48(1):31-54. doi: 10.1055/s-0041-1735454. Epub 2021 Oct 29.
Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3-4, and 7-8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin-antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis ( = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.
患有 2019 年冠状病毒病（COVID-19）即由严重急性呼吸系统综合征冠状病毒 2 引起的传染性疾病的患者入住重症监护病房（ICU）时有发生血栓的高风险，尽管确切的发病机制尚未阐明。在 PubMed 和 EMBASE 中进行的系统文献检索共确定了 18 项在 ICU COVID-19 患者中应用动态凝血检测的前瞻性研究。总体而言，这些研究显示出原发性止血功能正常或略有降低，血栓起始时间延长，但血栓硬度增加。凝血酶生成试验参数通常与对照组相当或在参考范围内。纤维蛋白溶解试验显示出增加的血栓阻力。只有六项研究将其发现与临床结局相关联。我们还前瞻性地纳入了 51 名入住 ICU 的 COVID-19 患者。在第 1、3-4 天和 7-8 天，使用血小板功能检测、旋转血栓弹性测定（ROTEM）、体内和体外凝血酶生成以及血栓溶解试验检查血样。在 30 天期间记录了血栓形成、出血和死亡率的数据。原发性止血与健康对照组相当，但 COVID-19 患者的 ROTEM 凝血时间比健康对照组长，最大血栓硬度比健康对照组高。体外凝血酶生成与健康对照组相似，而体内凝血酶生成标志物、凝血酶-抗凝血酶复合物（TAT 复合物）和凝血酶原片段 1+2（F1+2）在 ICU COVID-19 患者中高于健康对照组。所有时间点均存在纤溶受损。与未发生血栓形成的患者相比，发生血栓形成（ = 16）的患者中 TAT 复合物和 F1+2 水平明显更高。总之，只有少数先前的研究在 COVID-19 ICU 患者中应用了动态止血检测，但未能揭示与血栓形成发展之间的明确关联。在 ICU COVID-19 患者中，我们确认了正常的血小板聚集，而体内凝血酶生成增加，纤溶减少。血栓形成可能是由体内凝血酶形成增加引起的。
