What are the management options for bleeding due to heparin (Heparin) therapy?

Management of Heparin-Induced Bleeding

For bleeding due to heparin therapy, immediately stop all heparin and administer protamine sulfate at a dose of 1 mg per 100 units of heparin, with no more than 50 mg given slowly over any 10-minute period. 1

Immediate Assessment and Action

Stop heparin immediately when bleeding occurs, regardless of severity 2. The urgency of reversal depends on bleeding severity:

• Minor bleeding (e.g., oozing from IV sites, mild epistaxis): Simply discontinuing heparin is usually sufficient 2
• Major bleeding (e.g., hematemesis, melena, intracranial hemorrhage): Requires protamine sulfate reversal 2

Protamine Sulfate Reversal Protocol

Dosing calculation: 1

• Each 1 mg of protamine sulfate neutralizes approximately 100 USP units of heparin
• Maximum dose: 50 mg per 10-minute period
• The required protamine dose decreases over time as heparin is metabolized (heparin half-life approximately 30 minutes after IV injection)

Administration considerations: 1

• Give by slow IV infusion only
• Have resuscitation equipment immediately available—protamine can cause fatal anaphylactoid reactions
• Monitor closely during and after administration

Important limitation: Protamine fully neutralizes unfractionated heparin's anti-factor IIa activity but only partially neutralizes low molecular weight heparin's anti-factor Xa activity 2

Risk of Rebound Thrombosis

Weigh the thrombotic risk carefully before administering protamine 2. Reversal of anticoagulation carries risk of rebound thrombotic phenomena, particularly in patients with:

• Acute coronary syndromes 2
• Recent thromboembolism 2
• Mechanical heart valves 2

The decision to reverse must balance bleeding severity against the patient's underlying thrombotic risk on an individual basis 2.

Distinguishing HIT from Simple Bleeding

Critical pitfall: Do not confuse heparin-induced bleeding with heparin-induced thrombocytopenia (HIT), which requires completely different management 2, 3:

• Simple bleeding: Platelet count normal or mildly decreased, no thrombosis, responds to heparin cessation ± protamine 4
• HIT: Platelet count drops ≥50% from baseline (typically 5-10 days after heparin exposure), paradoxical thrombosis risk, requires immediate switch to non-heparin anticoagulant (argatroban, bivalirudin) 2, 3

If HIT is suspected (thrombocytopenia + thrombosis), calculate 4Ts score and switch to alternative anticoagulation immediately—do NOT simply stop anticoagulation 2, 3

Supportive Measures

For major bleeding: 2

• Transfuse packed red blood cells as needed for hemodynamic support
• Consider fresh frozen plasma if coagulopathy present
• Avoid platelet transfusions unless concurrent HIT is ruled out (platelets worsen HIT-related thrombosis) 3

Restarting Anticoagulation After Bleeding

Timing depends on thrombotic risk: 2

• High thrombotic risk (mechanical valve, recent VTE within 3 months, CHA₂DS₂-VASc ≥4): Consider bridging with IV unfractionated heparin once bleeding controlled, as its short half-life allows rapid reversal if rebleeding occurs 2
• Lower thrombotic risk: Temporary interruption acceptable until bleeding source addressed 2
• Consider switching to alternative anticoagulant (DOAC, warfarin) if supratherapeutic heparin dosing caused bleeding 2

Prevention of Future Bleeding

Monitoring strategies: 5, 6

• Continuous IV infusion causes less bleeding than intermittent boluses in high-risk patients 5
• Patients >60 years (especially women) require lower heparin doses 1
• Retroperitoneal bleeding risk increases with higher heparin levels measured by chromogenic substrate assay 6