Prolonged Coagulopathy Secondary to Superwarfarin Brodifacoum Rodenticide Ingestion

A 47 year old man presented to emergency room due to back pain, hematuria and persistent gum bleed for more than one week after dental procedure. He had also noted easy bruisability for the last two months. He was found to have elevated PT and PTT. On admission, his PT was >120 sec with INR > 9.9 and his PTT > 100 sec. The abnormal PT and PTT were completed corrected by the addition of normal plasma on mixing study. Factor assay showed factor II level 19%, factor VII 1.5%, factor IX 7.4%, factor × 15%, factor V 87%, factor VIII 140%, factor XI 96%, and factor XII 49%. Since he had no other medical conditions and no history of hepatic dysfunction that would cause his coagulopathy, superwarfarin toxicity was suspected. Blood toxicology screen was positive for superwarfarin compound brodifacoum. He received few units of FFP and was given a loading dose of 50 mg phytonadione (vitamin K) followed by 20 mg three times daily. His PT and INR normalized and gum bleeding and hematuria resolved. The patient was discharged from hospital. Patient denied any intentional ingestion of rat poison, any suicidal ideation or any conflicts within family. He was exposed to rodenticide at his workplace. During outpatient follow up, patient was again found to have elevated PT/INR and on questioning informed that he was taking Chinese herbal medications provided by his friends to facilitate excretion of the rat poison. Patient was advised to stop taking any alternative therapies. His phytonadione was increased to 240 mg/day for more than two months which have normalized his coagulopathy.

Human toxicity from ingestion of older rodenticides that contain warfarin is uncommon because these products contain less warfarin and the drug is rapidly metabolized. Newer derivates of warfarin (superwarfarins) brodifacoum, difethialone and difenicoum have been developed to overcome warfarin resistance. These compounds are more toxic to humans than warfarin because of their more avid binding to hepatic microsomes and longer duration of action. Brodifacoum and difenicoum are far more potent and have a much longer half-life than warfarin. The half-life of brodifacoum has been described as long as 30 days. Superwarfarins produce their anticoagulation effect by inhibiting the conversion of vitamin K1 2,3 epoxide to vitamin K1. This reaction is coupled to the carboxylation reaction required to produce the active form of prothrombin and the other vitamin K dependent clotting factors. There is increase in the vitamin K epoxide to vitamin K ratio and severely decreased activity of vitamin K dependent clotting factors. The duration of coagulation disturbance can be from few weeks to as long as few months. As illustrated by our patient, the treatment of superwarfarin posioning requires large doses of phytonadione, ranging from 50 – 800 mg/day administered for several months. Our patient has required daily 240 mg of phytonadione over two months to normalize his coagulopathy.

No relevant conflicts of interest to declare.