Department of Medicine, General Medicine and Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy.
Department of Medicine, Anaesthesia and Intensive Care Unit, Padova University Hospital, Padova, Italy.
Clin Chem Lab Med. 2021 Feb 4;59(7):1323-1330. doi: 10.1515/cclm-2021-0108. Print 2021 Jun 25.
Thrombin generation (TG) with and without thrombomodulin (TM) was evaluated in COVID-19 patients with different disease severity and thromboprophylaxis regimen, in order to understand the prothrombotic profile.
We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls.
Eighty-nine patients were included (mean age 60.4±16.1 years, 68.5% male); 33.7% admitted to ICU. Twenty-four patients (26.9%) were enrolled before thromboprophylaxis administration; 45 patients (50.6%) received standard and 20 (22.5%) intermediate sub-therapeutic dose thromboprophylaxis. Overall, patients with COVID-19 showed a TG profile comparable to that of healthy subjects (i.e. comparable peak height, endogenous thrombin potential [ETP] with and without TM). The only exception was lag time and time to peak, prolonged in COVID-19 patients vs. controls. MD patients showed a similar TG profile to healthy controls, and ICU patients showed significantly decrease ETP (p=0.030) compared to MD. As for thromboprophylaxis, TG profile was significantly increased in COVID-19 patients without thromboprophylaxis vs. controls and vs. those with thromboprophylaxis. In this latter group, ETP inhibition was significantly decreased (p=0.0003) and positively correlated with anti-Xa activity (r=0.49, p=0.0017). However, patients with thromboprophylaxis had similar TG profile vs. controls. Intermediate dose thromboprophylaxis more effectively inhibited TG in severe COVID-19 patients by increasing ETP inhibition via ETP with TM reduction vs. standard dose.
COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.
评估 COVID-19 患者在不同疾病严重程度和血栓预防方案下凝血酶生成（TG）和无血栓调节蛋白（TM）的情况，以了解其促血栓形成的特征。
我们连续纳入了确诊为 COVID-19 的住院于内科（MD）或重症监护病房（ICU）的患者，并纳入了 54 名健康对照者。
共纳入 89 名患者（平均年龄 60.4±16.1 岁，68.5%为男性）；33.7%的患者收入 ICU。24 名患者（26.9%）在开始血栓预防治疗前入组；45 名患者（50.6%）接受标准剂量和 20 名患者（22.5%）接受中剂量亚治疗剂量血栓预防治疗。总体而言，COVID-19 患者的 TG 谱与健康对照者相似（即峰值高度、有 TM 和无 TM 的内源性凝血酶潜能 [ETP]相似）。唯一的例外是Lag 时间和达到峰值时间，COVID-19 患者比对照组延长。MD 患者的 TG 谱与健康对照组相似，而 ICU 患者的 ETP 明显降低（p=0.030）。至于血栓预防治疗，未接受血栓预防治疗的 COVID-19 患者的 TG 谱与对照组和接受血栓预防治疗的患者相比明显增加。在后一组中，ETP 抑制显著降低（p=0.0003），并与抗-Xa 活性呈正相关（r=0.49，p=0.0017）。然而，接受血栓预防治疗的患者与对照组的 TG 谱相似。中剂量血栓预防治疗通过增加 ETP 抑制（通过 TM 减少的 ETP）更有效地抑制了重症 COVID-19 患者的 TG。
COVID-19 患者在诊断时表现出增加的 TG。标准血栓预防治疗将 TG 降低至健康对照组水平。中剂量亚治疗剂量血栓预防治疗通过减少 ETP 抑制（通过 TM 减少的 ETP）更有效地抑制了 TG。
