How is unfractionated heparin (UFH) given for pulmonary embolism in adults, including dosing, infusion rate, activated partial thromboplastin time (aPTT) monitoring, and adjustments for renal impairment or heparin‑induced thrombocytopenia?

Unfractionated Heparin Administration for Pulmonary Embolism

Unfractionated heparin for pulmonary embolism should be administered as an initial intravenous bolus of 80 IU/kg followed by continuous infusion at 18 IU/kg/hour, with subsequent dose adjustments based on aPTT monitoring to maintain levels at 1.5–2.5 times control (46–70 seconds). 1

Initial Dosing Protocol

Weight-Based Regimen (Preferred)

• Initial bolus: 80 IU/kg intravenous push 1
• Maintenance infusion: 18 IU/kg/hour by continuous IV infusion 1
• Target aPTT: 1.5–2.5 times control value (46–70 seconds) 1

Weight-based dosing achieves therapeutic anticoagulation faster and more reliably than fixed-dose regimens, which is critical given the high mortality of untreated PE. 1

Alternative Fixed-Dose Regimen (Less Preferred)

• Initial bolus: 5,000–10,000 IU 1
• Maintenance infusion: 1,300 IU/hour 1

The European Society of Cardiology explicitly recommends weight-adjusted dosing over fixed dosages because it provides more predictable anticoagulation. 1

aPTT Monitoring Schedule

Timing of aPTT checks is critical to prevent both recurrent thromboembolism and bleeding complications:

• First check: 4–6 hours after the initial bolus 1, 2
• After dose adjustments: 6–10 hours later 1, 2
• Once therapeutic: Daily monitoring 1, 2

Failure to achieve therapeutic aPTT (≥1.5 times control) within the first 24 hours is associated with a 25% risk of recurrent venous thromboembolism, making aggressive dose titration essential. 3

Dose Adjustment Algorithm

Use the following aPTT-based nomogram for systematic dose adjustments: 1

aPTT Result	Action Required
<35 seconds (<1.2× control)	Give 80 IU/kg bolus; increase infusion by 4 IU/kg/hour
35–45 seconds (1.2–1.5× control)	Give 40 IU/kg bolus; increase infusion by 2 IU/kg/hour
46–70 seconds (1.5–2.3× control)	No change—therapeutic range
71–90 seconds (2.3–3.0× control)	Reduce infusion by 2 IU/kg/hour
>90 seconds (>3.0× control)	Stop infusion for 1 hour, then reduce by 3 IU/kg/hour

This nomogram ensures systematic, evidence-based dose adjustments rather than arbitrary changes. 1

Transition to Oral Anticoagulation

Warfarin should be started simultaneously with heparin on day 1:

• Initial warfarin dose: 5–10 mg daily for 2 days (use 5 mg in elderly patients or those hospitalized; 10 mg in younger, otherwise healthy outpatients) 1
• Continue heparin for minimum 5 days regardless of INR 1, 4
• Discontinue heparin only when: INR ≥2.0 for at least 24 hours (preferably two consecutive measurements) 1
• Target INR: 2.0–3.0 1

The requirement for at least 5 days of heparin overlap exists because warfarin initially depletes protein C and S (anticoagulant factors) before depleting clotting factors, creating a transient prothrombotic state. 1

Special Populations and Adjustments

Renal Impairment

Unfractionated heparin is preferred over low-molecular-weight heparin in patients with severe renal failure (creatinine clearance <30 mL/min) because UFH is not renally cleared and has a short half-life that allows rapid dose adjustment. 1

Heparin-Induced Thrombocytopenia (HIT)

• Monitor platelet count at baseline and periodically during heparin therapy 1, 4
• If HIT develops, immediately discontinue all heparin products and switch to alternative anticoagulants (lepirudin, argatroban, or danaparoid) 5
• Do not use low-molecular-weight heparin as an alternative, as cross-reactivity occurs in most cases 5

Patients Requiring Primary Reperfusion

UFH is recommended over LMWH for patients in whom thrombolysis or surgical embolectomy is being considered because of its short half-life, ease of monitoring, and rapid reversal with protamine. 1

When to Initiate Heparin

Start anticoagulation immediately when PE is suspected, even before diagnostic confirmation, given the high mortality rate in untreated patients. 1, 6 The European Society of Cardiology emphasizes that in patients with high or intermediate clinical probability for PE, parenteral anticoagulation should be initiated while awaiting diagnostic test results. 1

Critical Pitfalls to Avoid

• Do not use fixed-dose heparin regimens when weight-based dosing is feasible—weight-adjusted protocols achieve therapeutic levels faster 1
• Do not stop heparin before 5 days regardless of INR, as premature discontinuation increases recurrence risk 1, 4
• Do not accept subtherapeutic aPTT values—failure to achieve aPTT ≥1.5× control is associated with 25% recurrence rate 3
• Do not delay anticoagulation while awaiting confirmatory testing in high-probability patients 1, 6
• Do not forget platelet monitoring—HIT can develop during therapy and requires immediate heparin cessation 1, 5

Alternative to UFH: Low-Molecular-Weight Heparin

While the question specifically asks about unfractionated heparin, it is important to note that LMWH or fondaparinux are actually preferred over UFH for most patients with PE because they carry lower risks of major bleeding and heparin-induced thrombocytopenia. 1 UFH remains the preferred choice only in specific situations: severe renal impairment, patients requiring thrombolysis, and those with severe obesity. 1