Superwarfarin poisoning: challenges still remain

Abstract

Superwarfarin (long-acting anticoagulant rodenticide) poisoning should be suspected in unexplained bleeding with prolonged prothrombin time, especially in the absence of another explanation. Diagnosis and treatment of this intoxication remain a challenge as the direct analysis of superwarfarin in serum is not always possible. Therefore, toxin bioavailability remains unknown and close monitoring and treatment for long periods are required to avoid serious bleeding complications. Here, we discuss a case of suspected superwarfarin poisoning to highlight the challenges in early diagnosis and the challenges we encountered in treatment management and ensuring compliance for long periods.

Keywords: Drugs and medicines; Exposures; Haematology (incl blood transfusion); Poisoning.

Figure 1

Data from 206 days of laboratory assessments for our patient. INR, international normalised ratio; IV, intravenous posology; PO, oral posology.

Figure 2

Mechanism of action of warfarin and superwarfarins. Vitamin K hydroquinone is oxidised to vitamin K epoxide by vitamin K-dependent γ-glutamyl carboxylase, which catalyses the post-translational carboxylation of specific glutamic acid residues to γ-carboxyglutamic acid in a variety of vitamin K-dependent proteins (VKP) including coagulation factors II, VII, IX and X, and protein S and C. Superwarfarins act similar to warfarin exerting their effect by inhibiting vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1). Inhibition of VKORC1 leads to reduced bioavailability of the metabolically active reduced form of vitamin K, resulting in decreased glutamyl carboxylation of VKP necessary for the final conformational structure of the proteins. The figure was prepared by the author (GM).