Managing Bleeding on Anticoagulants

Bleeding on an anticoagulant is managed by stopping the drug, local control, resuscitation, reversal when bleeding is major or life-threatening, and a plan to treat the cause. Match the reversal agent to the drug and the time of the last dose.

Severity. Minor: no intervention beyond local pressure. Clinically relevant: needs medical review or a delay in the next dose. Major: haemoglobin fall of 20 g/L or more, transfusion of 2 units or more, critical site (intracranial, spinal, retroperitoneal, intraocular, pericardial, intra-articular), or haemodynamic instability.

Initial steps. Stop the anticoagulant, apply pressure, protect the airway, give fluids and blood products as needed, and send blood for full blood count, creatinine, INR, aPTT, fibrinogen and anti-Xa (where available) and a group and crossmatch.

• Tranexamic acid 1 g intravenously over 10 minutes then 1 g over 8 hours for major bleeding (avoid in upper urinary tract bleeding and with a recent clot).
• Warfarin: phytomenadione (vitamin K) 5 to 10 mg by slow intravenous injection, with 4-factor prothrombin complex concentrate by INR: 2.0 to 3.9 give 25 units/kg; 4.0 to 5.9 give 35 units/kg; 6.0 or more give 50 units/kg (maximum 5000 units). If concentrate is not available, fresh frozen plasma 15 mL/kg.
• Dabigatran: idarucizumab 5 g intravenously (two doses of 2.5 g in 50 mL, each over 5 to 10 minutes, given within 15 minutes of each other). If unavailable, prothrombin complex concentrate 50 units/kg, and haemodialysis. Activated charcoal 50 g if the last dose was within 2 hours.
• Apixaban, rivaroxaban, edoxaban: andexanet alfa (low dose 400 mg bolus at 30 mg/min then 4 mg/min for up to 120 minutes; high dose 800 mg bolus then 8 mg/min for up to 120 minutes, chosen by drug, dose and time since last dose), or prothrombin complex concentrate 50 units/kg (maximum 5000 units). Activated charcoal 50 g if the last dose was within 2 to 4 hours.
• Unfractionated heparin: protamine sulphate 1 mg for each 100 units given in the last 2 to 3 hours (maximum 50 mg), slowly over 10 minutes.
• Enoxaparin: protamine 1 mg for each 1 mg of enoxaparin given within 8 hours, and 0.5 mg for each 1 mg if 8 to 12 hours; a second dose of 0.5 mg for each 1 mg if bleeding continues. Partial reversal only.
• Fondaparinux: no antidote; prothrombin complex concentrate or activated factor VII under specialist advice.
• Transfusion: red cells for haemoglobin under 70 g/L (under 80 g/L with cardiac disease); platelets if under 50 x 10^9/L in major bleeding; fibrinogen replacement if under 1.5 g/L.

Intracranial haemorrhage. Reverse immediately regardless of INR, aim for systolic blood pressure 140 mmHg, and involve neurosurgery.

Gastrointestinal bleeding. Endoscopy within 24 hours, proton pump inhibitor (pantoprazole 80 mg intravenously then 40 mg twice daily or by infusion), and reverse only for life-threatening bleeding.

Kidney impairment. Prolonged drug effect; dialysis may remove dabigatran but not the factor Xa inhibitors.

Special groups. Pregnant women bleeding on heparin need protamine and obstetric review. In East Africa, prothrombin complex concentrate, idarucizumab and andexanet alfa are often unavailable, so vitamin K, fresh frozen plasma, tranexamic acid, early surgery or endoscopy and rapid transfusion are the main tools.

Monitoring. Repeat INR 30 minutes after concentrate and at 6 and 24 hours, repeat full blood count every 6 hours, and monitor haemodynamics and urine output. Watch for thrombosis after reversal.

Referral and escalation. Call critical care, surgery or endoscopy, and haematology for major bleeding, haemodynamic instability, intracranial bleeding or lack of response to reversal.

Stopping. Keep the anticoagulant stopped until bleeding has been controlled and a restart decision has been made with the specialist.