Alternate Dosages for Anticoagulation Therapy in Pulmonary Embolism
For patients with pulmonary embolism, low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are the preferred first-line anticoagulants with specific dosing regimens for each medication. 1
Initial Anticoagulation Options
Low-Molecular-Weight Heparins (LMWHs)
LMWHs are administered subcutaneously and have several advantages over unfractionated heparin (UFH), including more predictable pharmacokinetics, fixed dosing, and no routine monitoring requirement.
Enoxaparin:
Dalteparin:
- 200 IU/kg once daily (maximum 18,000 IU) for first month
- 150 IU/kg once daily for months 2-6 (for cancer patients) 2
Nadroparin:
- Approved for PE treatment in some European countries 2
Tinzaparin:
- Fixed-dose subcutaneous administration once daily 4
Direct Oral Anticoagulants (DOACs)
DOACs offer fixed dosing, no routine monitoring, and fewer drug interactions compared to vitamin K antagonists.
Apixaban:
- 10 mg twice daily for 7 days, followed by
- 5 mg twice daily 1
Rivaroxaban:
- 15 mg twice daily for 21 days, followed by
- 20 mg once daily 1
Dabigatran:
- 150 mg twice daily after initial LMWH treatment 1
Edoxaban:
- 60 mg once daily
- 30 mg once daily if CrCl 30-50 mL/min or body weight <60 kg 1
Unfractionated Heparin (UFH)
UFH is preferred in specific clinical scenarios such as severe renal impairment, hemodynamic instability, or when thrombolysis is considered.
Intravenous bolus followed by continuous infusion:
- Initial dose: 80 units/kg IV bolus, followed by
- Continuous infusion: 18 units/kg/hour, adjusted to maintain aPTT 1.5-2.5 times normal 5
Intermittent IV injection:
- Initial dose: 10,000 units (undiluted or in 50-100 mL of 0.9% saline)
- Maintenance: 5,000-10,000 units every 4-6 hours 5
Subcutaneous administration:
- Initial dose: 5,000 units IV, followed by
- 10,000-20,000 units subcutaneously every 8 hours, or
- 8,000-10,000 units every 12 hours 5
Special Population Considerations
Renal Impairment
- For severe renal impairment (CrCl <30 mL/min):
- UFH is preferred, followed by vitamin K antagonists 1
- DOACs should be avoided or used with caution with dose adjustments
Pregnant Patients
- LMWH is the treatment of choice
- DOACs and vitamin K antagonists are contraindicated 1
Cancer Patients
- LMWH is recommended for at least 6 months
- Continue anticoagulation while cancer is active 1
Pediatric Patients
- Initial dose: 75-100 units/kg (IV bolus over 10 minutes)
- Maintenance dose:
- Infants: 25-30 units/kg/hour (infants <2 months have highest requirements)
- Children >1 year: 18-20 units/kg/hour 1
Transitioning Between Anticoagulants
Converting to Vitamin K Antagonists (e.g., Warfarin)
- Start warfarin at 5-10 mg (age-dependent)
- 10 mg for younger (<60 years), healthy outpatients
- 5 mg for older patients and hospitalized patients
- Continue parenteral anticoagulation for at least 5 days and until INR is 2.0-3.0 for two consecutive days 2, 5
Duration of Therapy
- Provoked PE (transient/reversible risk factors): 3 months
- Unprovoked PE or persistent risk factors: Extended therapy (>3 months)
- Recurrent PE: Indefinite anticoagulation 1
Clinical Pearls and Pitfalls
- LMWHs have been shown to be at least as effective as UFH in preventing recurrent venous thromboembolism, with a lower risk of major bleeding 2, 4
- Outpatient treatment with LMWH is safe and cost-effective for carefully selected patients who are hemodynamically stable and don't require thrombolysis 1, 6
- Regular monitoring of platelet counts, hematocrit, and occult blood in stool is recommended during heparin therapy 5
- When using UFH, dosage should be adjusted based on aPTT results (target: 1.5-2 times normal) 5
- For patients with antiphospholipid syndrome, vitamin K antagonists are preferred over DOACs 1
By following these dosing guidelines and considering patient-specific factors, clinicians can optimize anticoagulation therapy for pulmonary embolism while minimizing risks of recurrent thromboembolism and bleeding complications.