Combating clots in COVID-19

A hematologist recently provided her expert advice on preventing venous thromboembolism in patients hospitalized with COVID-19 in an interview with ACP Hospitalist.


One of the many perils faced by patients who are seriously ill with COVID-19 is the risk of venous thromboembolism (VTE). Patients who are admitted to the ICU in particular seem to have a dramatically elevated likelihood of clots, according to recent studies, such as those published earlier this month in Thrombosis Research and the Journal of Thrombosis and Haemostasis.

To learn more about this risk and how to mitigate it, ACP Hospitalist recently contacted Mary Cushman, MD, FACP, a hematologist at the University of Vermont Medical Center in Burlington and coauthor of a COVID-19 resource from the American Society of Hematology (ASH).

Q: What do we know so far about VTE risk in patients with COVID-19?

A: In patients with severe COVID-19 disease admitted to the hospital, the risk of VTE is increased. It has been suggested this might be as high as 25% in ICU patients but definitive studies are not available.

Q: What related testing/screening is appropriate in hospitalized patients?

A: We are recommending here at the University of Vermont Medical Center that D-dimer be checked in all patients on admission and that this be watched every day or two until patients stabilize. Careful monitoring for signs or symptoms of VTE is needed, and this should be addressed on admission and daily.

Q: Does COVID-19 require any modifications to VTE prophylaxis protocols that hospitalists need to know?

A: Every COVID-infected inpatient should be treated with pharmacologic VTE prophylaxis unless there is a contraindication. We at the University of Vermont use platelet count less than 30,000 [cells/µL] or recent active bleeding or high bleeding risk as a criterion to not give this in COVID-19. In that case, we use mechanical prophylaxis with intermittent pneumatic compression. Some institutions use weight-adjusted pharmacological prophylaxis with higher dose than normal for obese patients or severely obese patients, but there is no strong evidence for doing this in medical inpatients, even outside of COVID-19, so it cannot be broadly recommended.

Q: If everyone's getting prophylaxis, what should be done for patients with evidence of heightened risk (e.g., elevated D-dimer)?

A: The D-dimer elevation is part of the thrombo-inflammation that is happening in these patients, so using D-dimer the way we are used to, to think about VTE diagnosis, is problematic. In the course of the patient care, if the D-dimer rises rapidly, then care should be taken to address any symptoms of VTE with diagnostic tests if feasible. In the absence of ability to do diagnostic imaging, patients could be treated for VTE empirically if necessary, with the hope that they would be followed up with appropriate imaging at a time when they are not infectious and that can be done.

Q: What forms of prophylaxis are best? Is there any role for direct oral anticoagulants (DOACs)?

A: A resource on the ASH website suggests standard dosing of low-molecular-weight heparin (LMWH) on medical wards. This can be given once daily to minimize patient contact associated with unfractionated heparin injections twice daily, which is also a standard practice for medical inpatients. There is no role for DOACs because these aren't recommended for inpatient VTE prophylaxis, as they don't work any better than LMWH and have a higher bleeding risk, according to the American Society of Hematology guideline (published in 2018 in Blood Advances). In the ICU, there are a variety of thrombosis prevention protocols out there, some of which use higher doses for more aggressiveness. These are empiric and haven't been studied.

Q: Any other advice for hospitalists on this issue?

A: There is a great recent consensus paper people can refer to, published by JACC on April 15, and endorsed by several societies. Most specialty societies, including the American Society of Hematology, are also posting information on their sites.

Q: Is there ongoing research in this area? Will we learn more about it soon?

A: There are clinical trials being launched that apply different forms or doses of anticoagulants. I strongly recommend as many patients as possible be enrolled in clinical trials wherever possible. I am working to start such a multicenter randomized controlled trial, RAPID COVID COAG, and we welcome inquiries from interested sites.