Anticoagulant Overdose

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)

  • 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

Symptoms and Signs

• Hemoptysis

• Gross hematuria

• Bloody stools

• Hemorrhages into organs

• Widespread bruising

• Bleeding into joint spaces

Differential Diagnosis

• Liver disease

• Hemophilia

• Aspirin overdose

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 rivaroxaban

• 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

Diagnostic Procedures

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

Medications

Emergency and supportive measures

• Discontinue the drug at the first sign of gross bleeding

• Determine the PT

• Note: dabigatran, apixaban, betrixaban, edoxaban, and rivaroxaban do not predictably alter the PT; 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 (as high as 200 mg/day) may be required

• Vitamin K is not effective for treatment of the direct-acting oral anticoagulants

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

• Andexanet is FDA approved for reversal of the factor Xa inhibitors (apixaban, betrixaban, edoxaban, and rivaroxaban)

• The efficacy of fresh frozen plasma and clotting factor concentrates is uncertain

Follow-Up

• Serial evaluation of PT

Complications

• Bleeding

Prognosis

• Very good if no active bleeding and if close outpatient follow-up (and vitamin K treatment, if needed) is maintained (for several weeks—or longer after brodifacoum overdose)

When to Admit

• All patients with a history of superwarfarin ingestion for 2-day observation of the PT

• All patients with active bleeding