Background
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.
Methods
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.
Results
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.
Conclusion
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.
The association between coronavirus disease 2019 (COVID-19) pneumonia and venous thrombotic disorders is still unclear. We assessed the association between COVID-19 infection-related pneumonia and proximal deep-vein thrombosis (DVT) in a cohort of patients admitted to our hospital during the European outbreak in the front line of Cremona, Lombardy. In a single-center cross-sectional study, all patients hospitalized for more than 5 days in Internal Medicine Department with confirmed COVID-19 pneumonia received 2-point compressive ultrasound assessment (CUS) of the leg vein system during a single day. Ninety-four percent of patients received enoxaparin as standard pharmacological prophylaxis for venous thromboembolism. The presence of DVT was defined as incompressibility of popliteal or common femoral vein. Out of 121 patients with COVID-19 pneumonia (mean age 71.8, 66.3% males) hospitalized on March 31st, 70 stayed in hospital for over 5 days and 66 of them underwent CUS of deep venous system of the legs. The presence of asymptomatic DVT was found in 9 patients (13.6%). No symptomatic DVT was found. Patients with DVT showed mean age = 75.7 years, mean D-dimer levels = 4.02 ng/ml and all of them received enoxaparin for thromboprophylaxis, except one. Computed tomography pulmonary angiogram confirmed pulmonary embolism in five patients. One every seven patients with COVID-19-related pneumonia, hospitalized for more than 5 days, had asymptomatic proximal DVT and half of them had confirmed PE despite standard pharmacological thromboprophylaxis. This observational study suggests the need of an active surveillance through CUS in patients hospitalized with acute SARS-COV-2 and underline the need of a more intense thromboprophylaxis.
Oral anticoagulant therapy is recommended for the prevention and treatment of venous thromboembolism and to prevent stroke in non-valvular atrial fibrillation. Until a few years ago, vitamin K antagonists were the only drugs available, but direct oral anticoagulants have recently been introduced into clinical practice for the same clinical indications. Unlike the situation with VKAs, fixed-dose administration was proposed for DOACs, without the necessity for routine laboratory monitoring. However, in clinical practice a high inter-variability in DOAC plasma levels, independently of the type of drug and patient characteristics, was observed and the importance of measuring DOAC anticoagulant activity to support treatment decisions has therefore been recognized. We describe two clinical cases in order to highlight the role and importance of dabigatran-specific measurements to guide patient management in case of major complications.LEARNING POINTDirect oral anticoagulants (DOACs) have been used in clinical practice at fixed doses without laboratory monitoring.However, the importance of measuring DOAC anticoagulant activity to support treatment decisions, particularly in emergency conditions, has been recognized.The clinical value of DOAC measurement is highlighted in the two described cases where the anticoagulation level was taken into consideration when deciding on treatment.
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