Anesthesia Department, Hospital Clinic de Barcelona, Barcelona, Spain.
Hemostasis Department, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain.
J Thromb Thrombolysis. 2021 Feb;51(2):308-312. doi: 10.1007/s11239-020-02226-0. Epub 2020 Jul 15.
COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054-62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test.
Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection.
Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 10/L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score.
In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.
与 COVID-19 相关的凝血功能障碍与 D-二聚体水平升高有关，与高死亡率相关（Fei Z 等人，《中国武汉成人 COVID-19 住院患者的临床过程和死亡率的危险因素：一项回顾性队列研究》，柳叶刀（伦敦）395(10229):1054-62, 2020）。虽然 D-二聚体被认为是弥散性血管内凝血的标志物，但旋转血栓弹性测定（ROTEM）也可检测纤维蛋白溶解（Wright FL 等人，《严重 COVID-19 感染中纤维蛋白溶解功能关闭与血栓栓塞事件相关》，美国外科医师学会杂志（2020 年）。可从 https://pubmed.ncbi.nlm.nih.gov/32422349/ [引用日期 2020 年 6 月 14 日]获取；Schmitt FCF 等人，《脓毒症休克中早期发生急性纤维蛋白溶解功能关闭，与发病率和死亡率增加相关：一项观察性试点研究的结果》，《国际重症监护医学杂志》9(1):19, 2019）。我们描述了重症 COVID-19 患者的 ROTEM 图谱，并将其与标准实验室凝血试验进行了比较。
在伦理委员会批准（HCB/2020/0371）后，前瞻性纳入确诊为 COVID-19 并入住 ICU 的成年患者。所有患者均接受静脉血栓栓塞预防治疗；排除正在接受抗凝治疗的患者。在入住 ICU 后 24-48 小时同时进行标准实验室凝血试验和 ROTEM。在采集样本时计算序贯器官衰竭评估（SOFA）、弥散性血管内凝血（DIC）和脓毒症诱导的凝血障碍（SIC）评分。
共纳入 19 例患者，中位 SOFA 评分为 4（2-6），DIC 评分为 1（0-3），SIC 评分为 1.8（0.9）。中位纤维蛋白原、D-二聚体和血小板计数分别为 6.2（4.8-7.6 g/L）、1000（600-4200 ng/ml）和 236（136-364×10/L）。EXTEM 和 FIBTEM 检测中凝块硬度均高于正常值，而凝块溶解减少。ROTEM 或 D-二聚体参数与 SOFA 评分之间无显著相关性。
在 COVID-19 患者中，尽管 D-二聚体水平升高呈悖论性，但 ROTEM 模式表现为高凝状态伴纤维蛋白溶解能力降低。我们建议，在 COVID-19 患者中，肺部可能是 D-二聚体的主要来源，同时存在全身低纤维蛋白溶解状态。这一假设应通过未来的研究加以证实。
