Impact of the COVID-19 pandemic on England's national prescriptions of oral vitamin K antagonist (VKA) and direct-acting oral anticoagulants (DOACs): an interrupted time series analysis (January 2019-February 2021).

BACKGROUND: Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing. OBJECTIVE: To investigate DOAC prescription trends in England's community settings during the complete first wave of COVID-19 pandemic. METHODS: Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point. RESULTS: A 19% increase in mean DOAC's accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items, p = 0.008). The pre-existing upward trend in DOAC prescriptions slowed during the period (-427,000 items, p = 0.007). Apixaban was the most frequently used DOAC and had the largest step-change in March 2020 (+5 million items, p = 0.010). The mean monthly combined cost of DOACs and warfarin was higher during the period. DOAC prescription trends were consistent across England's regions. Conclusion: The overall oral anticoagulants use in this period was lower than expected, indicating a medical needs gap, possibly due to adherence issues. The potential clinical and logistical consequences warrant further study to identify contributing factors and mitigate avoidable risks.

Thromboelastography utilization for dabigatran reversal in a patient with acute kidney injury.

PURPOSE: This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury. SUMMARY: An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient's renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved. CONCLUSION: Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.

Direct oral anticoagulant plasma levels' striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents: The Cremona experience.

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.