What are the treatment guidelines for pulmonary embolism using heparin (unfractionated heparin) versus warfarin?

Pulmonary Embolism Treatment: Heparin vs Warfarin

Direct Answer

Both unfractionated heparin (UFH) and warfarin are essential components of pulmonary embolism treatment, but they serve different sequential roles: UFH (or LMWH) provides immediate anticoagulation for at least 5 days, followed by warfarin for long-term therapy, with mandatory overlap until INR reaches 2.0-3.0 for at least 2 consecutive days. 1

Initial Anticoagulation Strategy

Heparin as First-Line Therapy

• Immediate parenteral anticoagulation with heparin is mandatory because rapid anticoagulation can only be achieved with parenteral agents, not oral warfarin alone. 1
• A landmark study from the 1960s demonstrated that starting with warfarin alone (without heparin) resulted in a three-fold higher rate of recurrent VTE compared to initial heparin followed by warfarin. 1
• Anticoagulation should begin immediately in patients with suspected PE while awaiting diagnostic confirmation, given the high mortality in untreated patients. 1

Choice Between UFH and LMWH

For hemodynamically stable patients:

• Low-molecular-weight heparin (LMWH) is preferred over UFH due to more predictable pharmacokinetics, simpler fixed dosing, and lower risk of heparin-induced thrombocytopenia (HIT). 2, 3
• Approved LMWH regimens include enoxaparin 1.0 mg/kg every 12 hours or 1.5 mg/kg once daily, and tinzaparin 175 U/kg once daily. 1, 3
• Research confirms LMWH is at least as effective and safe as UFH for acute PE treatment. 4

For high-risk PE (shock or hypotension):

• Intravenous UFH is mandatory as the preferred initial anticoagulant, since LMWH and direct oral anticoagulants have not been tested in hemodynamically unstable patients. 1, 3, 5
• UFH allows for rapid reversal if thrombolysis becomes necessary. 3

For severe renal impairment:

• UFH is preferred over LMWH when creatinine clearance is <30 mL/min due to risk of LMWH bioaccumulation. 3

UFH Dosing Protocol

Initial Dosing

• Weight-based dosing is superior to fixed dosing for achieving therapeutic anticoagulation rapidly. 2
• Start with 80 U/kg IV bolus followed by 18 U/kg/hour continuous infusion. 1, 2, 3

Monitoring and Adjustment

• Check first aPTT 4-6 hours after starting infusion. 2, 3
• Target aPTT: 1.5-2.5 times control value (corresponding to heparin levels of 0.3-0.7 IU/mL by anti-factor Xa assay). 1, 2, 3
• Adjust doses according to the following algorithm: 1
  • aPTT <35 seconds (<1.2× control): Give 80 U/kg bolus; increase infusion by 4 U/kg/h
  • aPTT 35-45 seconds (1.2-1.5× control): Give 40 U/kg bolus; increase infusion by 2 U/kg/h
  • aPTT 46-70 seconds (1.5-2.3× control): No change (therapeutic range)
  • aPTT 71-90 seconds (2.3-3.0× control): Reduce infusion by 2 U/kg/h
  • aPTT >90 seconds (>3.0× control): Stop infusion for 1 hour, then reduce by 3 U/kg/h

HIT Monitoring

• Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia, which occurs in up to 5% of patients receiving UFH. 2

Transition to Warfarin

Timing and Overlap

• Start warfarin on the same day as heparin (day 1), not after heparin is stopped. 1, 3
• Continue parenteral heparin (UFH or LMWH) for at least 5 days minimum. 1, 2
• Do not stop heparin until INR is 2.0-3.0 for at least 2 consecutive days (some sources specify at least 24 hours at therapeutic INR). 1, 2, 3

Warfarin Dosing

• Start warfarin at 5 mg in older patients (>60 years) or those at bleeding risk; 7.5-10 mg may be used in younger, otherwise healthy outpatients. 1
• Lower starting doses (5 mg) are associated with less excessive anticoagulation compared to 10 mg in hospitalized patients. 1

Target INR

• Maintain INR between 2.0-3.0 (target 2.5). 6, 7

Duration of Anticoagulation

• Minimum 3 months for first episode of PE secondary to transient/reversible risk factor. 6, 7
• 6-12 months for first episode of idiopathic (unprovoked) PE. 6
• Long-term anticoagulation decisions beyond 3 months should be based on risk/benefit analysis considering recurrence risk versus bleeding risk. 7

Critical Pitfalls to Avoid

• Never start warfarin alone without heparin overlap – this increases recurrent VTE risk three-fold. 1
• Never stop heparin prematurely before achieving therapeutic INR for 2 consecutive days – this leaves a gap in anticoagulation coverage. 1, 3
• Never use LMWH in severe renal impairment (CrCl <30 mL/min) without switching to UFH or appropriate dose adjustment. 3, 5
• Never use LMWH in hemodynamically unstable patients – UFH is mandatory in shock/hypotension. 1, 3, 5
• Never fail to adjust UFH dosing based on aPTT – subtherapeutic anticoagulation increases recurrence risk. 3