Anticoagulant 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, 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 (prothrombin time [PT], international normalized ratio, partial thromboplastin time [PTT]) and these tests are of limited use

• Specialized coagulation studies including the HEMOCLOT^TM thrombin inhibitor and ecarin clotting time and the anti-factor Xa assays may be helpful but are not widely available

• The PT is increased within 12–24 hours (peak 36–48 hours) 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 PT)

  • 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, 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