Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

Clin Chem Lab Med. 2021 Feb 4;59(7):1323-1330. doi: 10.1515/cclm-2021-0108. Print 2021 Jun 25.


Objectives: 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.

Methods: We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls.

Results: 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.

Conclusions: 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.

Keywords: SARS-CoV-2; coagulopathy; hypercoagulability; inflammation; venous thromboembolism.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / therapeutic use*
  • COVID-19 / blood*
  • COVID-19 / complications
  • Female
  • Fondaparinux / therapeutic use
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2
  • Thrombin / analysis*
  • Thrombomodulin / analysis
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / prevention & control*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Thrombomodulin
  • Thrombin
  • Fondaparinux