What are the dosing recommendations for Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH) in patients with high-risk and moderate-risk Pulmonary Embolism (PE)?

Anticoagulation Dosing for High-Risk and Moderate-Risk Pulmonary Embolism

High-Risk PE (Hemodynamically Unstable)

For high-risk PE presenting with shock or hypotension, initiate unfractionated heparin (UFH) immediately with a weight-adjusted IV bolus of 80 U/kg followed by continuous infusion at 18 U/kg/hour. 1, 2, 3

UFH Dosing Protocol for High-Risk PE

• Initial bolus: 80 U/kg IV push 1, 2, 3
• Continuous infusion: 18 U/kg/hour 1, 2, 3
• Target aPTT: 1.5-2.5 times control (corresponding to anti-Xa 0.3-0.7 IU/mL) 1, 2, 3
• First aPTT check: 4-6 hours after initiation, then every 4 hours until stable 2, 3

aPTT-Based Dose Adjustment Algorithm

aPTT Result	Action
<35 sec (<1.2× normal)	80 U/kg bolus; increase rate by 4 U/kg/h [4]
35-45 sec (1.2-1.5× normal)	40 U/kg bolus; increase rate by 2 U/kg/h [4]
46-70 sec (1.5-2.3× normal)	No change [4]
71-90 sec (2.3-3.0× normal)	Decrease rate by 2 U/kg/h [4]
>90 sec (>3.0× normal)	Stop infusion for 1 hour, then decrease rate by 3 U/kg/h [4]

Rationale for UFH in High-Risk PE

• UFH is preferred over LMWH in high-risk PE because it allows rapid reversal with protamine if thrombolysis or surgical embolectomy becomes necessary 1, 2
• UFH has predictable clearance and can be monitored reliably in hemodynamically unstable patients 2, 4
• Systemic thrombolytic therapy is recommended for high-risk PE and requires UFH as the anticoagulant of choice 1

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Intermediate-Risk and Low-Risk PE (Hemodynamically Stable)

For intermediate-risk and low-risk PE, LMWH or fondaparinux is recommended over UFH for most patients. 1, 2

LMWH Dosing Options

Enoxaparin:

• 1 mg/kg subcutaneously every 12 hours (preferred for most patients) 1, 3
• Alternative: 1.5 mg/kg subcutaneously once daily 1
• For BMI ≥40 kg/m²: 0.8 mg/kg subcutaneously every 12 hours 1

Dalteparin:

• 200 U/kg subcutaneously once daily 1
• After 30 days, may reduce to 150 U/kg once daily 1

Tinzaparin:

• 175 U/kg subcutaneously once daily 2, 5

Fondaparinux Dosing (Weight-Based)

• <50 kg: 5 mg subcutaneously once daily 1
• 50-100 kg: 7.5 mg subcutaneously once daily 1
• >100 kg: 10 mg subcutaneously once daily 1

UFH Alternative for Intermediate/Low-Risk PE (When LMWH Contraindicated)

If LMWH cannot be used (severe renal impairment with CrCl <30 mL/min, severe obesity, or need for rapid reversibility):

Intravenous UFH:

• 80 U/kg bolus followed by 18 U/kg/hour infusion 1, 3
• Target aPTT 1.5-2.5 times control 1, 2

Subcutaneous UFH (unmonitored):

• Initial dose: 333 U/kg subcutaneously 1
• Maintenance: 250 U/kg subcutaneously every 12 hours 1

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Special Populations and Considerations

Severe Renal Impairment (CrCl <30 mL/min)

• UFH is preferred over LMWH due to risk of bioaccumulation 1, 2, 4
• Use IV UFH with standard weight-based dosing (80 U/kg bolus, 18 U/kg/hour) 2, 4, 3
• If LMWH must be used with CrCl 15-30 mL/min, use adapted dosing with anti-Xa monitoring 1

Cancer Patients

• LMWH is preferred over UFH for initial treatment 1, 6
• Enoxaparin 1 mg/kg every 12 hours or dalteparin 200 U/kg once daily 1
• Continue LMWH for at least 3-6 months (not just bridging to oral anticoagulation) 1, 6

Pregnancy

• LMWH is the anticoagulant of choice (DOACs and warfarin are contraindicated) 1
• Enoxaparin 1 mg/kg every 12 hours with anti-Xa monitoring 2
• Target anti-Xa levels: 0.6-1.0 IU/mL for twice-daily dosing 2

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Duration of Parenteral Anticoagulation

• Continue parenteral anticoagulation for at least 5 days 1, 2, 3
• Overlap with warfarin until INR 2.0-3.0 for at least 2 consecutive days 1, 3
• For DOACs (rivaroxaban, apixaban), parenteral anticoagulation may not be needed as these can be started immediately 1

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Monitoring Requirements

For UFH:

• aPTT every 4-6 hours initially, then daily once stable 2, 3
• Platelet count every 2-3 days to monitor for heparin-induced thrombocytopenia 1, 4
• Hematocrit and occult blood in stool periodically 3

For LMWH:

• Routine anti-Xa monitoring is NOT required for most patients 1, 2
• Consider anti-Xa monitoring in: severe renal impairment, pregnancy, extremes of body weight, or bleeding complications 2
• Target anti-Xa: 0.6-1.0 IU/mL (4 hours post-dose for twice-daily dosing) 2

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Common Pitfalls to Avoid

• Do not use LMWH in high-risk PE requiring potential thrombolysis – UFH allows rapid reversal 1, 2
• Do not use LMWH without dose adjustment in severe renal impairment (CrCl <30 mL/min) – risk of accumulation and bleeding 1, 2
• Do not delay anticoagulation while awaiting confirmatory imaging in high clinical probability PE – start immediately 1
• Do not underdose UFH – failure to achieve aPTT >1.5× control within 24 hours is associated with 25% recurrence rate 7
• Do not give intramuscular injections to patients on therapeutic anticoagulation – high risk of hematoma 3