What are warfarin and superwarfarin toxicity?

Updated: Jan 19, 2018
  • Author: Kent R Olson, MD, FACEP; Chief Editor: David Vearrier, MD, MPH  more...
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Answer

Overdose of the oral anticoagulant warfarin (Coumadin), or drug interactions with warfarin, can lead to toxicity. Similarly, toxicity can result from exposure to superwarfarins, which are long-acting anticoagulants used in rodenticides. [1, 2] (See Etiology and Prognosis.)

In the early 20th century, bis-hydroxycoumarin was discovered after livestock had eaten spoiled sweet clover and died of a hemorrhagic disease. Today, coumarin derivatives are used therapeutically as anticoagulants and commercially as rodenticides.

Warfarin is the most common oral anticoagulant in current use. Broad-ranging applications, such as in the treatment of patients with mechanical heart valves, chronic atrial fibrillation, deep venous thrombosis, pulmonary embolism, and dilated cardiomyopathy, have led to widespread exposure to this drug. (See Etiology and Epidemiology.) [3]

Additionally, although warfarin is no longer used primarily as a rodenticide, several long-acting coumarin derivatives (the so-called superwarfarin anticoagulants, such as brodifacoum, diphenadione, chlorophacinone, and bromadiolone) are used for this purpose and can produce profound and prolonged anticoagulation. Common commercial products containing superwarfarins include D-con Mouse Prufe I and II, Ramik, and Talon-G.

Blood levels of warfarin are neither readily available nor helpful. The anticoagulant effect is best quantified by baseline and daily repeated measurement of the prothrombin time (PT) and the International Normalized Ratio (INR), which may not be elevated until 1-2 days postingestion. (See Workup).

In the absence of serious or life-threatening hemorrhage, treatment with oral vitamin Kis recommended. Significant superwarfarin poisoning may require many weeks of vitamin K1 therapy. Active, serious hemorrhage should be treated with four-factor prothrombin complex concentrate (PCC), if available. Recombinant factor VIIa (rFVIIa) may be considered if PCC is not available. If neither PCC nor rFVIIa is not available, fresh frozen plasma may be administered instead. (See Treatment and Medication.) 


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