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在 COVID-19 患者中同时存在高 D 二聚体和低整体纤维蛋白溶解:这是怎么回事?

High D dimers and low global fibrinolysis coexist in COVID19 patients: what is going on in there?

机构信息

Anesthesia Department, Hospital Clinic de Barcelona, Barcelona, Spain.

Hemostasis Department, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain.

出版信息

J Thromb Thrombolysis. 2021 Feb;51(2):308-312. doi: 10.1007/s11239-020-02226-0. Epub 2020 Jul 15.

Abstract

BACKGROUD

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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