What is the recommended initial dose of unfractionated heparin for an adult with acute pulmonary embolism?

Unfractionated Heparin Dosing for Acute Pulmonary Embolism

For an adult with acute pulmonary embolism requiring unfractionated heparin, administer an initial intravenous bolus of 80 units/kg followed by a continuous infusion of 18 units/kg/hour, with dose adjustments based on aPTT monitoring to maintain a target of 1.5–2.5 times the control value. 1, 2, 3

Initial Dosing Protocol

• The bolus dose is 80 units/kg IV push, immediately followed by the maintenance infusion 1, 2
• The maintenance infusion rate is 18 units/kg/hour as continuous IV infusion 1, 2
• For patients over 70 kg, cap the initial bolus at 4,000 units and the infusion at 1,000 units/hour to prevent excessive anticoagulation 2
• The FDA-approved regimen for therapeutic anticoagulation lists 20,000–40,000 units per 24 hours (approximately 833–1,667 units/hour) as an alternative continuous infusion approach, though weight-based dosing achieves therapeutic levels more rapidly 3

Monitoring Requirements

• Obtain the first aPTT 4–6 hours after starting the infusion 1, 2
• Target aPTT should be 1.5–2.5 times the control value (approximately 50–70 seconds), which corresponds to anti-Factor Xa levels of 0.3–0.7 IU/mL 1, 2
• Repeat aPTT every 4–6 hours until stable in the therapeutic range, then daily 2
• Failure to achieve an aPTT >1.5 times control is associated with a 25% risk of recurrent venous thromboembolism, making adequate initial dosing critical 4

Dose Adjustment Algorithm

• Adjust the infusion rate based on aPTT results using a standardized protocol 1
• If aPTT remains subtherapeutic, administer additional bolus doses and increase the infusion rate according to established nomograms 1
• Continue monitoring aPTT every 4–6 hours after each dose adjustment until consistently therapeutic 2

Duration and Transition to Oral Anticoagulation

• Continue unfractionated heparin for at least 5–7 days 1
• Initiate oral anticoagulant (warfarin) on day 1 or as soon as possible, overlapping with heparin for at least 4–5 days 1, 3
• Discontinue heparin only after the INR has been ≥2.0 for at least 24 hours 1

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 receiving UFH 1
• Monitor hematocrit and test for occult blood in stool throughout therapy 3
• Major bleeding risk is present but comparable to LMWH when properly dosed 5, 6

When to Choose UFH Over LMWH

Important context: Low-molecular-weight heparin is superior to UFH for most stable PE patients, reducing mortality and major bleeding 7, 5. However, UFH is specifically indicated in these scenarios:

• Hemodynamic instability (shock or hypotension requiring possible thrombolysis or embolectomy) because UFH can be rapidly reversed with protamine 7
• Severe renal impairment (creatinine clearance <30 mL/min) because LMWH accumulates and increases bleeding risk 2, 7
• When thrombolysis is being considered or planned, to permit immediate reversal if needed 7
• Severe obesity where LMWH pharmacokinetics become unpredictable 7

Common Pitfalls to Avoid

• Using fixed-dose rather than weight-based dosing delays achievement of therapeutic anticoagulation and increases recurrence risk 1
• Failing to obtain the first aPTT at 4–6 hours may result in prolonged subtherapeutic anticoagulation 1, 2
• Discontinuing heparin before adequate oral anticoagulation (INR ≥2.0 for 24 hours) creates a gap in anticoagulation 1
• Not monitoring for HIT between days 4–14 can miss this life-threatening complication 1
• Using UFH in stable patients without specific contraindications to LMWH exposes them to higher mortality and bleeding risk compared to LMWH 7, 5