Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université de Paris, Paris, France.
Eur Rev Med Pharmacol Sci. 2020 Sep;24(17):9161-9168. doi: 10.26355/eurrev_202009_22866.
Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE).
We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis.
Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001].
Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.
COVID-19 可使患者易发生血栓形成，但其潜在机制仍不完全清楚。我们旨在研究危重症 COVID-19 患者中促凝因子与天然抗凝抑制剂之间的平衡，并评估止血参数在识别静脉血栓栓塞事件（VTE）风险患者中的作用。
我们进行了一项观察性研究，使用下肢超声（92%的患者）、计算机断层扫描肺动脉造影（6%）和两者（2%）定义 VTE 为深静脉血栓形成或肺栓塞。我们进行了全面的止血分析。
2020 年 3 月 11 日至 5 月 5 日期间，共纳入 92 例连续接受机械通气的 COVID-19 患者（年龄 62 岁[53-69]（中位数[25-75 百分位数]）；M/F 性别比为 2.5；体重指数 28 kg/m2[25-32]；既往高血压（52%）和糖尿病（30%））。入住重症监护病房（ICU）后，患者接受预防性（74%）或治疗性（26%）抗凝治疗。40 例（43%）患者诊断为 VTE。患者表现出炎症和促血栓形成的特征，包括明显升高的血浆纤维蛋白原（7.7 g/L[6.1-8.6]）、D-二聚体（3360 ng/mL[1668-7575]）、因子 V（166 IU/dL[136-195]）和因子 VIII 活性（294 IU/dL[223-362]）。我们发现抗凝蛋白 C 的活性和显色活性显著不一致，同时伴有蛋白 S 活性轻度降低。血浆 D-二聚体>3300 ng/mL 预测 VTE 存在的敏感性为 78%（95%置信区间[95%CI]，62-89），特异性为 69%（95%CI，55-81），阳性预测值为 66%（95%CI，51-79），阴性预测值为 80%（95%CI，65-90）[ROC 曲线下面积，0.779（95%CI，0.681-0.859），p=0.0001]。
机械通气的 COVID-19 患者表现为因子 V/VIII 活性明显增加与蛋白 C/S 途径耗竭之间的失衡。血浆 D-二聚体可能是床边怀疑 VTE 的有用生物标志物。
