Urgent Oral Anticoagulant Reversal

Oral anticoagulants are used for the prevention of stroke in atrial fibrillation (AF) as well as for the prevention and treatment of venous thromboembolism (VTE). Available oral anticoagulants include vitamin K antagonists (VKA; warfarin) and novel/non-VKA oral anticoagulants (NOACs; dabigatran, rivaroxaban, apixaban). The anticoagulant effect of warfarin is monitored using the international normalized ratio (INR) and can be reversed using vitamin K and coagulation factor replacement (plasma, prothrombin complex concentrates [PCC]).

NOACs have advantages over warfarin, including lack of need for routine monitoring, rapid onset of action, short half-lives and fewer drug interactions. Clinical experience regarding laboratory testing and reversal of anticoagulant effect is still being accumulated. Clinical evidence regarding use of non-specific hemostatic agents (PCC, activated PCC, recombinant factor VIIa [rVIIa]) is lacking in patients who are bleeding.  Idarucizumab, a specific reversal agent for dabigatran is now available in Canada for patients who are bleeding or require an urgent surgery or procedure.

Clinicians have questions about optimal management of clinically significant bleeding related to NOAC use. This CAEP Note serves as a guide for clinicians to optimally manage bleeding events or in urgent procedures in anticoagulated patients.

 


 

Definitions

Severe/Life-threatening bleeding – Intracranial hemorrhage, critical site (e.g. retroperitoneal, intra-spinal, intra-ocular, intra-articular), actual or impending hemodynamic compromise (e.g. massive GI bleed), clinically overt bleeding with hemoglobin decrease ≥20 g/L or administration of ≥2 units RBCs

Moderate bleeding – hemodynamically stable gastrointestinal bleeding, uncontrolled posterior epistaxis

Minor bleeding – subconjunctival hemorrhage, small bruising/lacerations, dental bleeding, anterior epistaxis, hemorrhoidal bleeding

Emergency surgery/procedure – <12 h (e.g. intracranial bleed, ruptured viscus, cardiac tamponade)

Urgent surgery/procedure – 12-24 h (e.g. hip fracture repair, acute cholecystitis)

 

Authors

Anil Chopra MD FRCP DABEM
Head and Medical Director, Emergency Medicine University Health Network Division Director
Emergency Medicine Associate Professor, Department of Medicine University of Toronto
Executive Member, Thrombosis Canada

Deborah Siegal MD MSc FRCPC
Clinical Scholar, Division of Hematology and Thromboembolism, McMaster University
CIHR Research Fellow

Mark Mensour MD CCFP EM ANAES FCFP
Associate Professor Northern Ontario School of Medicine
Canadian Association of Emergency Physicians Continuing Professional Development Chair
Emergency Medicine and Anaesthesiology Muskoka Algonquin Healthcare

SEVERE/LIFE-THREATENING BLEEDING

Examples: intracranial hemorrhage (ICH), active bleeding into a critical site (e.g. retroperitoneal, intra-spinal, intra-articular), major bleeding with or at risk for hemodynamic compromise (e.g. massive gastrointestinal [GI] bleed), bleeding associated with decrease in haemoglobin (Hb) ≥ 20 g/L, transfusion of ≥ 2 units of red blood cells (RBCs)

Initial Management

  1. Stabilize Patient
    1. NPO, intravenous access, intravenous isotonic fluids, monitors
  2. Identify site of bleeding and whether anticoagulant-related
  3. Apply local hemostatic measures (e.g. compression to bleeding site)
  4. Investigations
    1. ECG
    2. CT head without contrast STAT for suspected ICH
    3. Labs
      1. CBCaPTTINR, Group+Screen, creatinine
      2. NOAC Specific Assays (where available)
        Rivaroxaban-calibrated anti-Xa activity assay

MODERATE BLEEDING

Examples: hemodynamically stable gastrointestinal bleeding, uncontrolled posterior epistaxis, gross hematuria

Initial Management

  1. Assess patient stability
    1. NPO, intravenous access, intravenous isotonic fluids, monitors
  2. Identify site of bleeding and whether anticoagulant-related
  3. Apply local hemostatic measures (e.g. compression to bleeding site, clean and repair of laceration)
  4. Investigations
    1. ECG
    2. Labs
      1. CBCaPTTINR, Group+Screen, creatinine
      2. NOAC Specific Assays (where available)
        Rivaroxaban-calibrated anti-Xa activity assay
        Apixaban-calibrated anti-Xa activity assay

MINOR BLEEDING

Examples: subconjunctival hemorrhage, small bruises/lacerations, dental bleeding, anterior epistaxis, hemorrhoidal bleeding

Initial Management

  1. Identify site of bleeding and whether anticoagulant-related
  2. Apply local hemostatic measures (e.g. compression to bleeding site, clean and repair of laceration)
  3. Optional Investigations
    1. Labs
      1. CBC to ensure stability of hemoglobin and platelet count
      2. Creatinine to assess renal function (especially for dabigatran)
      3. INR for patients receiving warfarin
  4. Continue anticoagulant therapy
  5. Review the following
    1. Indication for anticoagulation, dose and frequency TC Tool
    2. Additional medications that interfere with haemostasis (e.g. antiplatelet therapies, non-steroidal anti-inflammatory drugs [NSAIDs])

URGENT INVASIVE PROCEDURE

Examples: lumbar puncture, chest tube insertion, paracentesis, thoracentesis

Initial Management

  1. Defer elective procedures if patient receiving anticoagulant therapy
    Periop Tool
  2. Assess for presence of anticoagulant
    1. INR for patients receiving warfarin
    2. NOAC specific assays (where available)
      Rivaroxaban-calibrated anti-Xa activity assay
      Apixaban-calibrated anti-Xa activity assay
      Dabigatran- Dilute thrombin time (Hemoclot®, ecarin clotting time)

      1. If NOAC-specific assays are unavailable use timing of last dose, half-life, and creatinine to determine likely presence of drug. Routine coagulation tests (e.g. INRaPTT) may not reliably detect clinically significant NOAC drug levels.

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