Ranucci Marco, Sitzia Clementina, Baryshnikova Ekaterina, Di Dedda Umberto, Cardani Rosanna, Martelli Fabio, Corsi Romanelli Massimiliano
Department of Cardiovascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, I-20097 San Donato Milanese, Milan, Italy.
Department of Biomedical Sciences for Health, Chair of Clinical Pathology, University of Milan, I-20133 Milan, Italy.
J Clin Med. 2020 Oct 28;9(11):3487. doi: 10.3390/jcm9113487.
Coronavirus Disease 2019 (COVID-19)-associated coagulopathy is characterized by a prothrombotic state not yet comprehensively studied. We investigated the coagulation pattern of patients with COVID-19 acute respiratory distress syndrome (ARDS), comparing patients who survived to those who did not. In this prospective cohort study on 20 COVID-19 ARDS patients, the following biomarkers were measured: thrombin generation (prothrombin fragment 1 + 2 (PF 1 + 2)), fibrinolysis activation (tissue plasminogen activator (tPA)) and inhibition (plasminogen activator inhibitor 2 (PAI-2)), fibrin synthesis (fibrinopeptide A) and fibrinolysis magnitude (plasmin-antiplasmin complex (PAP) and D-dimers). Measurements were done upon intensive care unit (ICU) admission and after 10-14 days. There was increased thrombin generation; modest or null release of t-PA; and increased levels of PAI-2, fibrinopeptide A, PAP and D-dimers. At baseline, nonsurvivors had a significantly ( = 0.014) higher PAI-2/PAP ratio than survivors (109, interquartile range (IQR) 18.1-216, vs. 8.7, IQR 2.9-12.6). At follow-up, thrombin generation was significantly ( = 0.025) reduced in survivors (PF 1 + 2 from 396 pg/mL, IQR 185-585 to 237 pg/mL, IQR 120-393), whereas it increased in nonsurvivors. Fibrinolysis inhibition at follow-up remained stable in survivors and increased in nonsurvivors, leading to a significant ( = 0.026) difference in PAI-2 levels (161 pg/mL, IQR 50-334, vs. 1088 pg/mL, IQR 177-1565). Severe patterns of COVID-19 ARDS are characterized by a thrombin burst and the consequent coagulation activation. Mechanisms of fibrinolysis regulation appear unbalanced toward fibrinolysis inhibition. This pattern ameliorates in survivors, whereas it worsens in nonsurvivors.
2019冠状病毒病（COVID-19）相关凝血病的特征是处于一种尚未得到全面研究的血栓前状态。我们调查了COVID-19急性呼吸窘迫综合征（ARDS）患者的凝血模式，比较了存活患者和未存活患者。在这项针对20例COVID-19 ARDS患者的前瞻性队列研究中，测量了以下生物标志物：凝血酶生成（凝血酶原片段1 + 2（PF 1 + 2））、纤溶激活（组织纤溶酶原激活物（tPA））和抑制（纤溶酶原激活物抑制剂2（PAI-2））、纤维蛋白合成（纤维蛋白肽A）以及纤溶程度（纤溶酶-抗纤溶酶复合物（PAP）和D-二聚体）。在重症监护病房（ICU）入院时及10 - 14天后进行测量。结果显示凝血酶生成增加；t-PA释放适度或无释放；PAI-2、纤维蛋白肽A、PAP和D-二聚体水平升高。基线时，非存活者的PAI-2/PAP比值显著（ = 0.014）高于存活者（109，四分位间距（IQR）18.1 - 216，对比8.7，IQR 2.9 - 12.6）。随访时，存活者的凝血酶生成显著（ = 0.025）降低（PF 1 + 2从396 pg/mL，IQR 185 - 585降至237 pg/mL，IQR 120 - 393），而非存活者则升高。存活者随访时的纤溶抑制保持稳定，非存活者则升高，导致PAI-2水平出现显著（ = 0.026）差异（161 pg/mL，IQR 50 - 334，对比1088 pg/mL，IQR 177 - 1565）。COVID-19 ARDS的严重模式以凝血酶爆发及随之的凝血激活为特征。纤溶调节机制似乎在纤溶抑制方向失衡。这种模式在存活者中改善，而在非存活者中恶化。
