Warfarin and related compounds (including ingredients of many commercial rodenticides, the so-called superwarfarins such as brodifacoum, difenacoum, and related compounds) inhibit the normal clotting system by blocking hepatic synthesis of vitamin K–dependent clotting factors. After ingestion of “superwarfarins,” inhibition of clotting factor synthesis may persist for several weeks or even months after a single dose. Direct-acting oral anticoagulants (DOACs) include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors apixiban, betrixaban, edoxaban, and rivaroxaban. Some of these, especially dabigatran, are largely eliminated by the kidney and may accumulate in patients with kidney dysfunction.
Excessive anticoagulation may cause hemoptysis, gross hematuria, bloody stools, hemorrhages into organs, widespread bruising, and bleeding into joint spaces.
A. Emergency and Supportive Measures
Discontinue the drug at the first sign of gross bleeding, and determine the prothrombin time (international normalized ratio, INR). The prothrombin time is increased within 12–24 hours (peak 36–48 hours) after overdose of warfarin or “superwarfarins.” Note: DOACs (dabigatran, apixiban, betrixaban, edoxaban, and rivaroxaban) do not predictably alter routine coagulation studies (prothrombin time, partial thromboplastin time, and INR), and these tests are of limited use. Specialized coagulation studies including the hemaclot and ecarin clotting assay and the anti-factor Xa activity may be helpful but are not widely available.
If the patient has ingested an acute overdose, administer activated charcoal.
In cases of warfarin and “superwarfarin” overdose, do not treat prophylactically with vitamin K—wait for evidence of anticoagulation (elevated prothrombin time). See Table 14–21 for the management of INR above therapeutic range. Doses of vitamin K as high as 200 mg/day have been required after ingestion of “superwarfarins.” Give fresh-frozen plasma, prothrombin complex concentrate, or activated factor VII as needed to rapidly correct the coagulation factor deficit if there is serious bleeding. If the patient is chronically anticoagulated and has strong medical indications for being maintained in that status (eg, prosthetic heart valve), give much smaller doses of vitamin K (1 mg orally) and fresh-frozen plasma (or both) to titrate to the desired prothrombin time. If the patient has ingested brodifacoum or a related superwarfarin, prolonged observation (over weeks) and repeated administration of large doses of vitamin K may be required.
2. Direct-acting oral anticoagulants
Vitamin K does not reverse the anticoagulant effects of the DOACs. Idarucizumab has been approved by the FDA for reversal of the thrombin inhibitor dabigatran; andexanet is approved for reversal of the factor Xa inhibitors apixaban, edoxaban, betrixaban, and rivaroxaban. If specific reversal agents are unavailable, evidence supports the use of prothrombin complex concentrates or activated prothrombin complex concentrates for reversal of factor Xa inhibitors.
et al. Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum. Am J Hematol. 2019;94:697.