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For further information, see CMDT Part 38-19: Anticoagulants Overdose

Key Features

  • Warfarin and related compounds (including ingredients of many commercial rodenticides) inhibit the normal clotting system by blocking hepatic synthesis of vitamin K–dependent clotting factors

  • Half-life of the "superwarfarins" (such as brodifacoum, difenacoum and related compounds) used as rodenticides can be weeks or longer

  • Direct-acting oral anticoagulants (DOACs)

    • Dabigatran (direct thrombin inhibitor)

    • Apixaban, betrixaban, edoxaban, and rivaroxaban (factor Xa inhibitors)

    • Some of these, especially dabigatran, are largely eliminated by the kidney and may accumulate in patients with kidney disease

Clinical Findings

  • Hemoptysis

  • Gross hematuria

  • Bloody stools

  • Hemorrhages into organs

  • Widespread bruising

  • Bleeding into joint spaces

Diagnosis

  • DOACs do not predictably alter routine coagulation studies (PT, PTT 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

  • The PT is increased within 12–24 h (peak 36–48 h) after an overdose of warfarin or superwarfarins

  • After ingestion of brodifacoum, difenacoum, and related rodenticides (even after a single dose), inhibition of clotting factor synthesis may persist for several weeks or even months

Treatment

Emergency and supportive measures

  • Discontinue the drug at the first sign of gross bleeding

  • Determine the PT

Activated charcoal

  • Administer activated charcoal, 60–100 g orally or via gastric tube, mixed in aqueous slurry if the patient has ingested an acute overdose

Specific treatment

  • Warfarin

    • In cases of warfarin and "superwarfarin" overdose, do not treat prophylactically with vitamin K—wait for evidence of anticoagulation (elevated prothrombin time)

    • Vitamin K

      • Doses as high as 200 mg/day have been required after ingestion of "superwarfarins"

      • Smaller doses (1 mg orally) should be given to patients who receive long-term anticoagulation who cannot discontinue the medication; fresh-frozen plasma may be required in addition; titrate to the desired prothrombin time

      • Repeated administration of large doses of vitamin K as well as prolonged observation (over weeks) may be required if the patient has ingested brodifacoum or a related superwarfarin

    • 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

  • DOACs

    • Vitamin K does not reverse the anticoagulant effects of the DOACs

    • Idarucizumab is FDA-approved 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 (PCC) or activated prothrombin complex concentrates (APCC) for reversal of factor Xa inhibitors

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