What is the heparin infusion protocol for treating Pulmonary Embolism (PE) with Unfractionated Heparin (UFH)?

Heparin Infusion Protocol for Pulmonary Embolism

For acute pulmonary embolism, initiate unfractionated heparin with an intravenous bolus of 80 U/kg followed by continuous infusion at 18 U/kg/hour, adjusting doses to maintain aPTT at 1.5-2.5 times control (corresponding to anti-factor Xa levels of 0.3-0.7 IU/mL). 1, 2, 3

Initial Dosing and Administration

• Administer an initial IV bolus of 80 U/kg followed immediately by continuous infusion at 18 U/kg/hour 1, 2, 3
• For a standard 68 kg patient, this translates to approximately 5,440 units bolus and 1,224 units/hour infusion 3
• Alternative dosing includes a 5,000-10,000 unit bolus followed by 1,250-1,300 U/hour infusion, though weight-based dosing achieves therapeutic levels more rapidly 1, 2, 4

Monitoring Protocol

• Check the first aPTT 4-6 hours after initiating the infusion 1, 2, 3
• Target aPTT should be 1.5-2.5 times the control value (typically 45-75 seconds), which corresponds to anti-factor Xa activity of 0.3-0.7 IU/mL 1, 5, 2
• After any dose adjustment, recheck aPTT in 6-10 hours 1
• Once therapeutic, monitor aPTT daily 1
• Recent evidence suggests anti-factor Xa monitoring may be superior to aPTT, particularly when aPTT results are unreliable, with target levels of 0.3-0.7 units/mL 5, 6, 7

Dose Adjustment Algorithm

Adjust the infusion rate based on aPTT results using the following protocol 5, 2:

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

Duration and Transition to Oral Anticoagulation

• Continue heparin for at least 5-7 days 1, 2, 8, 9
• Initiate warfarin on day 1 (same day as heparin) and overlap for minimum 5 days 1, 2, 6
• Discontinue heparin only after INR is ≥2.0 for at least 24 hours (preferably 2 consecutive days) 1, 2, 6
• Target INR for warfarin is 2.0-3.0 1, 5

Safety Monitoring

• Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia (HIT), which occurs in up to 5% of patients 2
• Periodically monitor hematocrit and check for occult blood in stool throughout therapy 3
• Failure to achieve therapeutic aPTT within the first 24 hours is associated with a 25% risk of recurrent thromboembolism 9
• A first anti-Xa level <0.3 units/mL is associated with increased mortality risk 7

Special Clinical Situations

When UFH is Preferred Over LMWH:

• Hemodynamically unstable patients or those with massive PE requiring potential thrombolysis (UFH allows rapid reversal) 6
• Severe renal impairment (CrCl <30 mL/min) due to unpredictable LMWH pharmacokinetics 1, 5, 6
• End-stage renal disease on hemodialysis (UFH has predictable clearance) 5
• Patients who may require urgent procedures 2

Thrombolysis Considerations:

• Stop heparin before administering thrombolytic therapy 1
• Resume heparin at maintenance dose (without bolus) after thrombolysis completion 1, 6
• Consider thrombolysis for patients with cardiogenic shock or persistent hypotension 5

Common Pitfalls and Caveats

• Do not use intramuscular administration due to frequent hematoma formation 3
• Avoid using LMWH in severe renal dysfunction without appropriate dose adjustment or anti-Xa monitoring 6
• Do not delay anticoagulation while awaiting confirmatory imaging in patients with high clinical suspicion 6
• Ensure proper mixing when adding heparin to IV solutions by inverting the container at least 6 times 3
• Weight-based dosing is superior to fixed dosing and achieves therapeutic anticoagulation more rapidly 2, 7
• Heparin resistance can occur due to nonspecific binding to plasma proteins (fibrinogen, factor VIII, vitronectin); consider anti-Xa monitoring in these cases 8, 4
• Achieving therapeutic anticoagulation rapidly is critical: 93% of patients should sustain therapeutic levels by 48 hours 7