Unexpected acute pulmonary embolism in an old COVID-19 patient with warfarin overdose: a case report

Maxime Coutrot; Maxime Delrue; Bérangère S Joly; Virginie Siguret

doi:10.1093/ehjcr/ytab206

Unexpected acute pulmonary embolism in an old COVID-19 patient with warfarin overdose: a case report

Eur Heart J Case Rep. 2021 Jun 5;5(6):ytab206. doi: 10.1093/ehjcr/ytab206. eCollection 2021 Jun.

Authors

Maxime Coutrot^{1

2

3}, Maxime Delrue^{4

5}, Bérangère S Joly^{4

5}, Virginie Siguret^{4

6}

Affiliations

¹ Department of Anaesthesiology, Critical Care Medicine and Burn Unit, AP-HP, Saint Louis and Lariboisière University Hospitals, 1 Avenue Claude Vellefaux, 75010 Paris, France.
² INSERM UMR-S 942, 41 boulevard de la Chapelle, 75475 Paris Cedex 10, Lariboisière Hospital, Paris, France.
³ FHU PROMICE, 2 Rue Ambroise Paré, 75010 Paris‌, France.
⁴ Service d'hématologie biologique, Hôpital Lariboisière, 2rue Ambroise Pare ´,75010 Paris, Université de Paris, Paris, France.
⁵ EA 3518, Institut de Recherche Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, Université de Paris, Paris, France.
⁶ INSERM UMR-S 1140 Innovations thérapeutiques en Hémostase, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 Paris CEDEX 06, Université de Paris, Paris, France.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 disease is strongly associated with a high incidence of thrombotic events. Anticoagulation could be a cornerstone in successfully managing severe forms of coronavirus disease 2019 (COVID-19). However, optimal anticoagulant dosing in elderly patients is challenging because of high risk of both thrombosis and bleeding.

Case summary: We present here the case of an 89-year-old patient receiving warfarin for atrial fibrillation and valvular heart disease, admitted to the intensive care unit for respiratory failure due to COVID-19. The patient presented with a severe epistaxis associated with warfarin overdose [international normalized ratio (INR) > 10]. After a successful initial reversal using vitamin K per os, INR values greatly fluctuated up to 10, requiring repeated administrations of vitamin K. Despite starting low-molecular-weight heparin therapy at therapeutic dose as soon as INR value was below 2.0, the patient further developed an acute bilateral and proximal pulmonary embolism concomitantly with a sharp D-dimer increase. The combination of azithromycin intake, a known inhibitor of CYP2C9, with the presence of CYP2C9*2 and -1639G>A VKORC1, two variants associated with warfarin hypersensitivity, have likely contributed to explain the warfarin overdose and the difficulty to reverse warfarin effect in this patient.

Discussion: This case report illustrates the complexity of COVID-19 pathophysiology and its management for physicians, especially in patients receiving vitamin K antagonists (VKAs). Infection, concurrent medication use, and pharmacogenetic factors involved in VKA metabolism and pharmacodynamics may lead to a loss of control of anticoagulation. Pulmonary embolism should still be considered in COVID-19 patients even with effective or overdosed anticoagulant therapy.

Keywords: COVID-19; Case report; D-dimer; Overdose; Pulmonary embolism; Warfarin.

Publication types

Case Reports