As long as antiviral agents are necessary for treating severe coronavirus disease 2019 (COVID-19) respiratory syndrome (SARS-CoV-2), replacing direct oral anticoagulants (DOACs) with alternative parenteral antithrombotic strategies may help to prevent bleeding complications, according to research published in the Journal of Thrombosis and Haemostasis.

Researchers in Italy noted that some patients hospitalized for severe COVID-19 infection were already being treated with DOACs including dabigatran, apixaban, rivaroxaban, and edoxaban; however, these treatments may have unintended interactions with antiviral agents used against COVID-19, including increased DOAC plasma levels, which in turn increase the risk for hemorrhage. In addition, metabolic alterations linked to severe COVID-19 may lead to thrombotic events and uncontrolled bleeding.

The authors compared hospitalization C-trough DOAC plasma levels with those measured at a thrombosis center before hospitalization at Cremona Hospital in northern Italy.

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Of the 1039 patients with COVID-19 who were eligible for antiviral therapy and who were admitted to the hospital between February 22, 2020, and March 15, 2020, for SARS-CoV-2, 32 patients were already receiving a DOAC. Twenty of these patients discontinued the DOAC based on physician decision. Of the 12 patients (8 men; mean age, 80 years) who continued DOAC treatment, 5 patients were receiving apixaban, 3 were receiving rivaroxaban, 3 were receiving edoxaban, and 1 was receiving dabigatran. Half of these patients were receiving low-dose DOAC.

On average, C-trough levels were 6.14 times greater during hospitalization than beforehand, with an increase range of 65.2% in a 74 year old man receiving apixaban to 3056.2% in a 77 year old man receiving rivaroxaban.

“In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge,” the authors concluded.

Reference

Testa S, Prandoni P, Paoletti O, et al. Direct oral anticoagulant plasma levels’ striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents. The Cremona experience [published online April 23, 2020]. J Thromb Haemost. doi: 10.1111/jth.14871