Dicumarol and other natural anticoagulants are found in sweet clover. Coumarin derivatives are used both therapeutically and as rodenticides. Warfarin (Coumadin) is used widely as a therapeutic anticoagulant but is no longer popular as a rodenticide because rats and mice have become resistant. The most common anticoagulant rodenticides available today contain long-acting “superwarfarins” such as brodifacoum, diphacinone, bromadiolone, chlorophacinone, difenacoum, pindone, and valone, which have profound and prolonged anticoagulant effects.
Mechanism of toxicity. All these compounds inhibit vitamin K 2,3-epoxide reductase and vitamin K quinone reductase, two enzymes responsible for the conversion of vitamin K to its active form, a necessary cofactor in the hepatic synthesis of coagulation factors II, VII, IX, and X. Only the synthesis of new factors is affected, and the anticoagulant effect is delayed until currently circulating factors have been degraded. Peak effects usually are not observed for 2–3 days because of the long half-lives of factors IX and X (24–60 hours).
The duration of anticoagulant effect after a single dose of
is usually 2–7 days. (See also Table II–61.)
Superwarfarin products may continue to produce significant anticoagulation for weeks to months after a single ingestion.
Toxic dose. The toxic dose is highly variable.
Generally, a single small ingestion of
(eg, 10–20 mg) will not cause serious intoxication (most warfarin-based rodenticides contain 0.05% warfarin). In contrast, chronic or repeated ingestion of even small amounts (eg, 2 mg/d) can produce significant anticoagulation. Patients with hepatic dysfunction, malnutrition, or a bleeding diathesis are at greater risk.
Superwarfarins are extremely potent and can have prolonged effects even after a single small ingestion. However, in a large study of accidental superwarfarin ingestions in children, no serious cases of anticoagulation occurred.
Multiple drug interactions are known to alter the anticoagulant effect of warfarin (see Table II–60 for examples of drug-drug interactions with warfarin).
Table II-60 Warfarin Interactions (Selected Examples) |Favorite Table|Download (.pdf)
Table II-60 Warfarin Interactions (Selected Examples)
Increased Anticoagulant Effect
Decreased Anticoagulant Effect
Nonsteroidal anti-inflammatory agents
Selective serotonin reuptake inhibitors
Clinical presentation. Excessive anticoagulation may cause ecchymoses, subconjunctival hemorrhage, bleeding gums, or evidence of internal hemorrhage (eg, hematemesis, melena, hematochezia, menorrhagia, or hematuria). The most immediately life-threatening complications are massive GI bleeding and intracranial hemorrhage.
Anticoagulant effects from warfarin may be apparent within 15 hours, but with superwarfarins, peak effects commonly are delayed for up to 2 days after ingestion.
Evidence of continuing anticoagulant effects from warfarin may persist for 5 days, whereas anticoagulation from superwarfarins may persist for several weeks, or even months.
Diagnosis is based on the history and evidence of ...