What is the recommended heparin (unfractionated heparin) infusion protocol after thrombolysis in patients with pulmonary embolism?

Heparin Infusion Protocol After Thrombolysis in Pulmonary Embolism

After thrombolytic therapy for pulmonary embolism, initiate unfractionated heparin at 18 U/kg/hour (approximately 1,280 IU/hour for a 70 kg patient) as a continuous infusion WITHOUT a bolus dose, but only after the aPTT falls below twice the upper limit of normal. 1

Critical Timing: When to Start Heparin

Do not start heparin immediately after completing thrombolysis. 1 This is a common and dangerous pitfall that significantly increases bleeding risk without providing additional benefit. 1

• Wait until the aPTT is less than 2 times the upper limit of normal before initiating the heparin infusion. 1
• This delay allows the systemic fibrinolytic state from thrombolysis to resolve, reducing hemorrhagic complications. 1

Initial Dosing Protocol

• Start at 18 U/kg/hour (approximately 1,280 IU/hour for a 70 kg patient) as a continuous intravenous infusion. 1
• Do NOT give a bolus dose when transitioning from thrombolysis to heparin. 1
• Target aPTT: 1.5-2.3 times control (46-70 seconds). 1

Dose Adjustment Algorithm

Check aPTT approximately every 4 hours initially, then at appropriate intervals once stable. 2 Adjust the infusion rate based on the following protocol:

• aPTT <35 seconds (<1.2× control): Give 80 U/kg bolus; increase infusion by 4 U/kg/hour 1
• aPTT 35-45 seconds (1.2-1.5× control): Give 40 U/kg bolus; increase infusion by 2 U/kg/hour 1
• aPTT 46-70 seconds (1.5-2.3× control): No change—this is the therapeutic range 1
• aPTT 71-90 seconds (2.3-3.0× control): Decrease infusion by 2 U/kg/hour 1
• aPTT >90 seconds (>3.0× control): Stop infusion for 1 hour, then decrease by 3 U/kg/hour 1

Mandatory Monitoring Requirements

• Check aPTT every 4 hours during initiation, then at appropriate intervals once stable. 2
• Monitor platelet count every 2-3 days to detect heparin-induced thrombocytopenia. 1
• Monitor hematocrit and test for occult blood in stool throughout therapy. 2

Duration and Transition to Oral Anticoagulation

Continue heparin for at least 5 days AND until INR ≥2.0 for at least 24 hours on two consecutive measurements. 1, 3

• Start warfarin simultaneously with heparin initiation at 5-10 mg daily. 1, 3
• Target INR: 2.0-3.0 throughout treatment. 1, 3
• Do not discontinue heparin until both the 5-day minimum duration is met AND the INR has been therapeutic (2.0-3.0) for at least 24-48 hours. 3

Special Considerations for High-Risk PE

Intravenous unfractionated heparin is mandatory (not low molecular weight heparin) for patients with hemodynamic instability (shock or hypotension) who received thrombolysis. 1

Bleeding Risk and Complications

• Major bleeding occurs in approximately 2% of appropriately anticoagulated patients. 1
• This risk increases to 10% in high-risk patients. 1
• The delayed initiation protocol (waiting for aPTT normalization) and avoidance of bolus dosing are specifically designed to minimize this risk after thrombolysis. 1

Common Pitfalls to Avoid

• Never start heparin immediately after thrombolysis completion—this dramatically increases bleeding risk. 1
• Never give a bolus dose when transitioning from thrombolysis to heparin—the continuous infusion alone is sufficient. 1
• Never discontinue heparin before meeting BOTH criteria: minimum 5 days AND therapeutic INR for 24-48 hours, as premature discontinuation increases recurrent thromboembolism risk. 3
• Failure to achieve adequate anticoagulation (aPTT >1.5 times control) is associated with a 25% risk of recurrent venous thromboembolism. 4