What is the recommended treatment for pulmonary embolism using heparin (unfractionated heparin) or low molecular weight heparin (LMWH)?

Treatment of Pulmonary Embolism with Heparin: LMWH vs Unfractionated Heparin

Either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) is appropriate for the initial treatment of pulmonary embolism (PE), with LMWH preferred in most cases due to its more predictable pharmacokinetics and lower risk of complications. 1

Risk Stratification and Initial Approach

Before selecting the anticoagulant, risk stratification is essential:

1. High-risk PE (with hemodynamic instability/shock)

   • UFH is recommended as the initial anticoagulant 1
   • Initial bolus: 80 units/kg or 5,000-10,000 IU 2
   • Maintenance: 18 units/kg/hour or 1,300 IU/hour 2
   • Target: APTT 1.5-2.5 times control (45-75 seconds) 2

2. Non-high-risk PE (hemodynamically stable)

   • LMWH or fondaparinux is preferred 1
   • LMWH dosing: 1 mg/kg every 12 hours SC or 1.5 mg/kg once daily SC 2

Advantages of LMWH over UFH

LMWH is preferred over UFH for most patients with PE because:

• Lower risk of major bleeding 1, 3
• Lower risk of heparin-induced thrombocytopenia (HIT) 1
• More predictable pharmacokinetics - quickly and consistently therapeutic 1
• No need for routine monitoring of anti-Xa levels 1
• Potential for outpatient management in selected low-risk patients 1

When to Use UFH Instead of LMWH

UFH should be used instead of LMWH in specific situations:

1. Patients with high-risk PE requiring thrombolysis or embolectomy 1
2. Severe renal dysfunction (CrCl <30 mL/min) 1, 2
3. Severe obesity 1
4. Hemodynamic instability requiring vasopressors 1

Monitoring and Adjustment of UFH

When using UFH:

• Check APTT in 4-6 hours after initial bolus 2
• After any dose change, check APTT in 6-10 hours 2
• Once therapeutic, check APTT daily 2
• Many patients on UFH are subtherapeutic or supratherapeutic 1, 4
  • Only 22% of APTT values within therapeutic range in one study 4
  • 44% above and 33% below therapeutic range 4

Duration of Initial Parenteral Anticoagulation

• Continue parenteral anticoagulation for at least 5 days 2
• Overlap with vitamin K antagonist (warfarin) until INR ≥2.0 for at least 24 hours 2
• If transitioning to a DOAC (direct oral anticoagulant), parenteral anticoagulation may be shorter or not needed depending on the specific DOAC 1, 2

Common Pitfalls and Caveats

1. Delayed therapeutic anticoagulation: UFH often takes longer to reach therapeutic levels (average 594 minutes in one study) 4

2. Excessive volume loading: Cautious volume optimization (<500 mL over 15-30 min) is recommended as aggressive volume expansion may worsen RV function 1

3. Inappropriate use of UFH: Using UFH in patients who would benefit more from LMWH increases risk of complications 4

4. Monitoring failures: Inadequate APTT monitoring leads to suboptimal therapy 4

5. Special populations:

   • Pregnancy: LMWH is preferred as it doesn't cross the placenta 1, 2
   • Cancer: LMWH is traditionally preferred for at least 6 months, though newer DOACs (apixaban, edoxaban, rivaroxaban) are now considered effective alternatives 2, 3

Conclusion for Clinical Practice

For most patients with PE, LMWH provides a more predictable anticoagulant effect with fewer complications compared to UFH. However, UFH remains the anticoagulant of choice for high-risk PE patients with hemodynamic instability, those requiring thrombolysis, and those with severe renal dysfunction. The decision between LMWH and UFH should be guided by patient characteristics, clinical presentation, and planned interventions.