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Anticoagulation in COVID-19

Updated: Oct 7, 2022

Anticoagulation in COVID-19

The overall prevalence of VTE in patients with COVID‐19 was estimated at 14.1% (95% CI, 11.6‐16.9) based on 66 studies in a systematic review and meta-analysis [1]. When stratified by the performance of ultrasound screening for VTE. the prevalence was 40.3% (95% CI, 27.0‐54.3) in those who were screened and 9.5% (95% CI, 7.5‐11.7) in those who were not screened.

There are more than 75 ongoing trials investigating the effect of aspirin, anticoagulation, and fibrinolytic therapy on COVID-19 patients in different doses and settings. Of those, only few have been published so far. These studies have been summarized in a presentation that you can downloaded from this link (for members only).

The initial results of the RECOVERY trial (not published yet) showed that there is no mortality benefit of adding aspirin to the management of patients with severe COVID-19 who were admitted to the hospital or the intensive care unit. A mortality rate of 17% was noticed in each group.

Despite the wide use of direct oral anticoagulants (DOAC) in the outpatient setting as well as the hospitalized patients, no trials have been published as of September 2, 2021. It is certainly logical to consider these agents for selected patients, however, no specific recommendations can be made till results of these trials are showing safety and efficacy. The ACTIV 4b trial is planned to recruit around 7000 patients investigating the effect of low dose and therapeutic dose of apixaban on COVID-19 patients.

The INSPIRATION trial revealed that the intermediate dose anticoagulation with Low Molecular Weight Heparin (LMWH) has no effect on the composite outcome of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days in patients admitted to the intensive care unit [2].

The ATTACC investigators in a study published in the NEJM revealed that in the moderately ill patients, therapeutic-dose heparin or LMWH appeared to increase the probability of survival until hospital discharge with a reduced need for organ support. However, more major bleeding occurred with heparin or LMWH than with thromboprophylaxis [3]. In the critical care setting, same investigators revealed that therapeutic-dose heparin or LMWH did not improve the primary outcome of days without organ support in the critically ill patients and was associated with more major bleeding complications than usual-care prophylaxis [4].

In conclusion, It seems that selected group of patients may benefit of full anticoagulation but has to start early enough before organ damage occurs. Individualized and risk-adjusted approach is advised until more evidence of clear benefit is available.



  1. Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis. Res Pract Thromb Haemost. 2020 Sep 25;4(7):1178–91. doi: 10.1002/rth2.12439. Epub ahead of print. PMID: 33043231; PMCID: PMC7537137.

  2. INSPIRATION Investigators. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Apr 27;325(16):1620-1630. doi: 10.1001/jama.2021.4152. PMID: 33734299; PMCID: PMC7974835.

  3. ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):790-802. doi: 10.1056/NEJMoa2105911. Epub 2021 Aug 4. PMID: 34351721; PMCID: PMC8362594.

  4. REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Aug 26;385(9):777-789. doi: 10.1056/NEJMoa2103417. Epub 2021 Aug 4. PMID: 34351722; PMCID: PMC8362592.


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