Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 38-19: Anticoagulants Overdose + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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 Download Section PDF Listen +++ +++ 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 + Treatment Download Section PDF Listen +++ +++ 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 + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +Berling I et al. Warfarin poisoning with delayed rebound toxicity. J Emerg Med. 2017 Feb;52(2):194–6. [PubMed: 27838137] + +Cuker A et al. Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum. Am J Hematol. 2019 Jun;94(6):697–709. [PubMed: 30916798] + +Dobesh PP et al. Antidotes for reversal of direct oral anticoagulants. Pharmacol Ther. 2019 Dec;204:107405. [PubMed: 31521696] + +Levine M et al. Assessing bleeding risk in patients with intentional overdoses of novel antiplatelet and anticoagulant medications. Ann Emerg Med. 2018 Mar;71(3):273–8. [PubMed: 29032872] + +Pollack CV Jr et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Aug 6;373(6):511–20. [PubMed: 26095746] + +Siegal DM et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015 Dec 17; 373(25):2413–24. [PubMed: 26559317] + +Zhang XY et al. Reversal of direct oral anticoagulants. Br J Hosp Med (Lond). 2017 Mar 2;78(3):165–9. [PubMed: 28277769]