edoxaban and Coronavirus-Infections

Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization.. All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization.. Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period.. DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. 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.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antithrombins; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Dabigatran; Darunavir; Drug Interactions; Drug Monitoring; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Italy; Lopinavir; Male; Pandemics; Patient Safety; Pneumonia, Viral; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Thiazoles

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first reported in Wuhan, China in December 2019, and is ongoing pandemic. While a majority of patients with SARS-CoV-2 infection shows asymptomatic or mild disease, hospitalized patients can develop critical condition, such as pneumonia, sepsis, and respiratory failure. Some cases deteriorate into sever systemic disease and multiorgan failure. Many patients of severe COVID-19 show hypercoagulable state and complicate with venous thromboembolism and atrial thrombosis. We herein reported a case of COVID-19 who developed cerebral venous thrombosis (CVT) co-incidence with pulmonary thromboembolism (PTE). A 56-year-old Japanese man was presented with fever and malaise and diagnosed with COVID-19. He was treated with ciclesonide and azithromycin, but his respiratory condition deteriorated. Thus, systemic corticosteroids and favipiravir were initiated and these treatments resulted in afebrile state, improving malaise and respiratory failure. However, he suddenly developed severe headache and vomiting with increased concentration of D-dimer. Brain CT and MRI showed typical images of CVT in the left transvers sinus and CT pulmonary angiography showed PE. Administration of unfractionated heparin followed by edoxaban treatment reduced the levels of D-dimer and improved his clinical presentation and thrombosis. Monitoring coagulopathy is important in COVID-19 patients and in case of venous thromboembolism, including cerebral venous system, appropriate anticoagulant therapy should be initiated.

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pyridines; SARS-CoV-2; Thiazoles; Tomography, X-Ray Computed; Venous Thrombosis