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Key Features

Essentials of Diagnosis

  • Prolonged prothrombin time (PT)

General Considerations

  • 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

    • Dabigatran (direct thrombin inhibitor)

    • Rivaroxaban, apixiban, and edoxaban (factor Xa inhibitors)

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

Clinical Findings

Symptoms and Signs

  • Hemoptysis

  • Gross hematuria

  • Bloody stools

  • Hemorrhages into organs

  • Widespread bruising

  • Bleeding into joint spaces

Differential Diagnosis

  • Liver disease

  • Hemophilia

  • Aspirin overdose

Diagnosis

Laboratory Tests

  • The PT is increased within 12–24 h (peak 36–48 h) after an overdose of warfarin or superwarfarins but is not as predictably abnormal after overdose of dabigatran or rivaroxiban

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

Diagnostic Procedures

  • Obtain daily PT/INR for at least 2 days after ingestion to rule out excessive anticoagulation

Treatment

Medications

Emergency and supportive measures

  • Discontinue the drug at the first sign of gross bleeding

  • Determine the PT

  • Note: dabigatran, rivaroxiban, apixiban, and edoxaban do not predictably alter the prothrombin time; however, a normal INR suggests no significant toxicity

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

  • If the PT is elevated, give phytonadione (vitamin K1), 10–25 mg orally, and increase the dose as needed to restore the PT to normal

  • Do not treat prophylactically—wait for the evidence of anticoagulation (elevated PT)

  • 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 has been receiving anticoagulation therapy long-term for a medical indication (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 PT

  • 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

  • Vitamin K is not effective for treatment of the direct-acting oral anticoagulants dabigatran, rivaroxaban, apixiban, and edoxaban

  • Idarucizumab is approved by the FDA as a reversal agent for dagibatran

  • Andexanet is FDA approved for reversal of the factor Xa ...

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