Initial Anticoagulation for Acute Pulmonary Embolism
For hemodynamically stable patients with acute PE, initiate low-molecular-weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH), while for hemodynamically unstable patients, use UFH immediately. 1
Risk Stratification Determines Heparin Choice
High-Risk (Massive) PE with Hemodynamic Instability
- Start UFH immediately in patients with systolic blood pressure <90 mmHg or cardiogenic shock 1, 2
- UFH is preferred because fondaparinux has not been tested in hemodynamically unstable patients 3
- Administer systemic thrombolysis immediately (rtPA 100 mg over 2 hours) alongside anticoagulation 4, 2
- If thrombolysis is contraindicated or fails, proceed to surgical pulmonary embolectomy 1, 2
Common pitfall: Do not use rivaroxaban or other NOACs in acute PE requiring thrombolysis or pulmonary embolectomy, as the FDA label specifically contraindicates their use in hemodynamically unstable patients 5
Intermediate-Risk and Low-Risk PE (Hemodynamically Stable)
- Prefer LMWH or fondaparinux over UFH as the initial parenteral anticoagulant 1
- Fondaparinux is explicitly recommended over UFH for most intermediate- or low-risk PE patients 3
- LMWH demonstrates comparable efficacy to UFH with potentially lower recurrent thromboembolism rates (13% vs 44% in one study) 6
Specific Dosing Regimens
LMWH (Enoxaparin)
- Administer 1 mg/kg subcutaneously twice daily 7
- No routine monitoring required 7, 6
- Research shows major bleeding rates of 3% with LMWH versus 8% with UFH 6
Fondaparinux
- Weight-adjusted fixed dosing: 3
- <50 kg: 5.0 mg subcutaneously once daily
- 50-100 kg: 7.5 mg subcutaneously once daily
100 kg: 10.0 mg subcutaneously once daily
- Major bleeding rate 1.3% (comparable to UFH at 1.1%) 3
- No platelet monitoring required 3
UFH (When Indicated)
- Bolus: 70-100 units/kg IV 8
- Continuous infusion: 15-25 units/kg/hour 8
- Target aPTT 1.5-2.0 times control (not the older 1.5-2.5 times) 8
Renal Function Considerations
Severe Renal Impairment
- Fondaparinux is absolutely contraindicated if creatinine clearance <20 mL/min 3
- Consider alternative anticoagulation if CrCl <30 mL/min 3
- Assess renal function before initiating fondaparinux given renal clearance 3
- UFH becomes the preferred option in severe renal failure as it is not renally cleared 1
Absolute Contraindications to Anticoagulation
When anticoagulation is contraindicated (e.g., active intracranial hemorrhage), consider temporary vena cava filter placement to bridge the period until anticoagulation becomes safe 9
Transition to Oral Anticoagulation
NOAC Preference
- NOACs are preferred over vitamin K antagonists when transitioning to oral therapy 1
- Rivaroxaban can be started immediately without parenteral overlap in stable patients 5
- Do not use NOACs if severe renal impairment (CrCl <30 mL/min), antiphospholipid antibody syndrome, pregnancy, or lactation 1
VKA Approach (When NOACs Contraindicated)
- Begin warfarin on day 1 or 2 of heparin therapy 8
- Continue parenteral anticoagulation for ≥5 days and until INR 2.0-3.0 for 2 consecutive days 4
- Warfarin dosing: 10 mg daily in younger patients (<60 years), ≤5 mg in older patients 4
- Target INR 2.0-3.0 (reduced from older 2.5-3.5 range) 8
Duration of Anticoagulation
- Minimum 3 months for all PE patients 1
- Discontinue after 3 months if first PE provoked by major transient/reversible risk factor 1, 2
- Continue indefinitely for unprovoked PE or recurrent VTE 1, 2
- Lifelong warfarin (not NOACs) for antiphospholipid antibody syndrome 2
Special Populations
Cancer Patients
- LMWH is superior to NOACs and should be continued indefinitely while cancer is active 2