What is the recommended heparin (unfractionated heparin) dosing regimen for the treatment of thrombus?

Heparin Dosing for Thrombus Treatment

For treatment of venous thromboembolism, initiate unfractionated heparin with an intravenous bolus of 80 units/kg followed by a continuous infusion of 18 units/kg/hour, targeting an aPTT of 1.5-2.5 times control (typically 46-70 seconds). 1, 2, 3

Initial Dosing Protocol

Weight-based dosing is mandatory as it significantly reduces recurrent thromboembolism compared to fixed-dose regimens. 2, 4

• Bolus dose: 80 units/kg IV push 1, 2, 3
• Initial infusion rate: 18 units/kg/hour as continuous IV infusion 1, 2, 3
• Target aPTT: 1.5-2.5 times control value (typically 46-70 seconds), corresponding to anti-Xa levels of 0.3-0.7 IU/mL 1, 2

The American College of Chest Physicians and European Society of Cardiology both endorse this weight-based approach as superior to fixed dosing. 1, 2

Monitoring and Dose Adjustments

First aPTT measurement should occur 4-6 hours after the initial bolus, with subsequent monitoring after each dose change and daily once therapeutic. 1, 2, 3

Use the following standardized adjustment protocol based on aPTT results: 1

• aPTT < 35 seconds (< 1.2 × control): Give 80 units/kg bolus, increase infusion by 4 units/kg/hour 1
• aPTT 35-45 seconds (1.2-1.5 × control): Give 40 units/kg bolus, increase infusion by 2 units/kg/hour 1
• aPTT 46-70 seconds (1.5-2.3 × control): No change - therapeutic range 1
• aPTT 71-90 seconds (2.3-3.0 × control): Decrease infusion by 2 units/kg/hour 1
• aPTT > 90 seconds (> 3.0 × control): Stop infusion for 1 hour, then decrease infusion by 3 units/kg/hour 1

Achieving therapeutic aPTT within 24 hours is critical - failure to do so is associated with 25% recurrence rate versus 2% when therapeutic levels are reached early. 2, 4, 5

Duration and Transition to Oral Anticoagulation

• Continue heparin for minimum 5 days regardless of INR 1, 2, 3
• Overlap with warfarin for at least 4-5 days 1, 2, 5
• Discontinue heparin only when INR ≥ 2.0 for at least 24 hours 1, 2, 3

The European Society of Cardiology emphasizes that starting warfarin alone without heparin results in three-fold higher recurrent VTE rates. 1

Alternative Fixed-Dose Regimen

When patient weight is unavailable, the FDA-approved alternative is: 3

• Initial bolus: 5,000 units IV
• Continuous infusion: At least 32,000 units/24 hours (minimum 1,333 units/hour)

However, this fixed-dose approach is inferior to weight-based dosing and should only be used when weight cannot be obtained. 2, 4

Special Populations

Morbidly Obese Patients (> 150 kg)

Standard weight-based protocols with maximum dose caps can cause dangerous delays in achieving therapeutic anticoagulation. 6 Consider using adjusted body weight: dosing weight = IBW + 0.3(ABW - IBW) or IBW + 0.4(ABW - IBW) rather than capping doses. 6

Severe Renal Impairment (CrCl < 30 mL/min)

Unfractionated heparin is preferred over low-molecular-weight heparin as it does not accumulate with renal dysfunction. 1, 4

Heparin Resistance

If requiring ≥ 35,000 units/day to maintain therapeutic aPTT, switch monitoring to anti-Xa levels (target 0.3-0.7 IU/mL) rather than aPTT. 4

Critical Safety Considerations

Monitor platelet counts every 2-3 days from day 4 through day 14 to detect heparin-induced thrombocytopenia (HIT), which occurs in up to 5% of patients. 4, 3 History of HIT is an absolute contraindication to unfractionated heparin - use argatroban, bivalirudin, or fondaparinux instead. 4, 3

Active bleeding is an absolute contraindication except in disseminated intravascular coagulation. 3

Common Pitfalls to Avoid

• Using fixed doses instead of weight-based dosing leads to significantly higher recurrence rates 2, 4
• Failing to achieve therapeutic aPTT within 24 hours increases both mortality and recurrence 2, 4
• Discontinuing heparin before adequate warfarin overlap (INR ≥ 2.0 for 24 hours) causes treatment failure 2, 3
• Not validating your institution's aPTT reagent against anti-Xa levels can result in incorrect therapeutic ranges 4
• Capping maximum doses in obese patients without using adjusted body weight formulas delays therapeutic anticoagulation 6
• Ignoring warfarin's effect on aPTT - warfarin directly prolongs aPTT by approximately 20 seconds for each 1.0 increase in INR, which can lead to inappropriate heparin dose reductions during overlap therapy 7