Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12466-12479. doi: 10.26355/eurrev_202012_24043.
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated.
Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days.
At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02).
SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.
严重急性呼吸综合征冠状病毒(SARS-CoV-2)感染可能导致纤维蛋白溶解受损的高凝状态。我们进行了一项单中心观察性研究,旨在分析伴有标准实验室和粘弹性测试的重症监护病房(ICU)COVID-19 患者的凝血模式。研究了感染发作时和全身抗凝治疗 7 天后是否存在凝血障碍。
2020 年 2 月 29 日至 3 月 30 日期间,意大利一家大学医院的 ICU 收治了 40 例连续 SARS-CoV-2 患者,他们符合急性呼吸窘迫综合征标准。他们接受了全剂量抗凝治疗,包括皮下注射依诺肝素 0.5mg·kg-1 ,每日两次;皮下注射未分馏肝素 7500 单位,每日三次;或低强度肝素输注。入院时和 7 天后测量血栓弹性图(TEG)和实验室参数。
基线时,患者表现出纤维蛋白原活性升高[rTEG-Ang 80.5°(78.7 至 81.5);TEG-ACT 78.5sec(69.2 至 87.9)]和最大血凝块强度振幅增加[FF-MA 42.2mm(30.9 至 49.2)]。凝血酶生成的酶相时间无变化[CKH-K 和 CKH-R,分别为 1.1min(0.85 至 1.3)和 6.6min(5.2 至 7.5)]。在所有研究人群中,均观察到 30 分钟时的凝块溶解不足(LY30)。标准凝血参数在生理范围内:[INR 1.09(1.01 至 1.20),aPTT 34.5sec(29.7 至 42.2),抗凝血酶 97.5%(89.5 至 115)]。然而,血浆纤维蛋白原[512.5mg·dl-1(303.5 至 605)]和 D-二聚体水平[1752.5ng·ml-1(698.5 至 4434.5)]持续高于参考范围。全剂量抗凝治疗 7 天后,平均 TEG 参数与基线时无差异(rTEG-Ang p=0.13,TEG-ACT p=0.58,FF-MA p=0.24,CK-R p=0.19,CKH-R p=0.35),并观察到白细胞计数、血小板计数和 D-二聚体持续增加(白细胞计数 p<0.01,中性粒细胞计数 p=0.02,淋巴细胞计数 p<0.01,血小板计数 p=0.13<0.01,D-二聚体水平 p=0.02)。
急性呼吸窘迫综合征的 SARS-CoV-2 患者表现出纤维蛋白原活性升高、D-二聚体水平升高和最大血凝块强度增加。血小板计数、纤维蛋白原和标准凝血试验不能提示弥散性血管内凝血。尽管进行了全剂量抗凝治疗,但 7 天后血栓弹性图异常仍持续存在。