PO05 - Challenges with warfarin management in COVID-19 patients

Background: The coronavirus disease (COVID-19) has been associated with biochemical abnormalities in coagulation such as mild prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), elevations in D-dimer and fibrinogen resulting in increased incidences of venous thromboembolism reported whereas in Singapore, arterial thrombosis was noted in post COVID-19 infected migrant workers.

Aims: We would like to present two case reports of mild COVID-19 infection, their associated coagulation abnormalities and challenges with warfarin management during admission.

Methods: Clinical observation and presentation of two case reports.

Results: In the absence of severe COVID-19 infection, interacting medications or significant liver dysfunction, INR increased to 3.5 and 4.2, respectively, at day 12 of infection for the 2 cases, and remained elevated for 4 to 5 days despite warfarin omission. aPTT was also noted to be elevated. Anti-phospholipid (aPL) antibodies such as lupus anticoagulant (LAC) was not detected in Case 2. This decreased the likelihood of falsely elevated INR due to presence of transient LAC.
Warfarin sensitivity, calculated by dividing INR by average daily dose of warfarin, was increased in both cases when comparing prior to admission (PTA) and at discharge. Both cases had warfarin sensitivity increasing from 1.10 PTA to 1.28 at discharge and from 0.43 PTA to 0.6 upon discharge, respectively. No clinically significant thromboembolism or bleeding manifestations requiring intervention or blood product transfusion were required in both cases.

Conclusion(s): We recommend that close INR monitoring with warfarin titration is required for patients with COVID-19 infection. If monitoring and titration of warfarin is anticipated to be difficult, alternative therapeutic options such as low molecular weight heparin (LMWH) therapy can be considered in the absence of contraindications. Close follow up is recommended upon discharge with anticipation that warfarin dose need to be up-titrated back to baseline maintenance doses once patients have recovered from COVID-19 infection.