What is the half-life of heparin (unfractionated heparin)?

Half-Life of Unfractionated Heparin

The half-life of unfractionated heparin is dose-dependent, ranging from approximately 30 minutes after a low IV bolus dose (25 units/kg) to 60 minutes with a moderate dose (100 units/kg) and up to 150 minutes with a high dose (400 units/kg). 1

Pharmacokinetic Properties

Unfractionated heparin (UFH) demonstrates complex pharmacokinetics that significantly impact its clinical use:

• Dose-dependent clearance: Heparin is cleared through two mechanisms:

  1. A rapid saturable mechanism involving binding to endothelial cell receptors and macrophages
  2. A slower first-order mechanism that is primarily renal

• Non-linear kinetics: At therapeutic doses, the rapid saturable mechanism predominates, resulting in non-linear pharmacokinetics where both intensity and duration of effect increase disproportionately with dose 1

• Bioavailability factors:

  • IV administration: 100% bioavailability with immediate peak concentration and onset of action 2
  • Subcutaneous administration: Reduced bioavailability at lower doses, but nearly complete at high therapeutic doses (>35,000 units/24h) 1

Factors Affecting Heparin Half-Life

Several factors can influence heparin's half-life and anticoagulant effect:

• Plasma protein binding: Heparin binds to various plasma proteins besides antithrombin, reducing its anticoagulant activity and contributing to variability in response 1

• Endothelial binding: Binding to endothelial cells and macrophages further complicates pharmacokinetics 1

• Patient factors:

  • Age: Patients over 60 years may have higher plasma levels and longer aPTT times compared to younger patients 2
  • Disease state: Patients with pulmonary embolism may have significantly shortened heparin half-life 3

Clinical Implications

The variable half-life of heparin has important clinical implications:

• Monitoring requirements: Due to its unpredictable effect and variable half-life, UFH typically requires monitoring via aPTT or ACT, especially at therapeutic doses 1

• Dosing considerations:

  • For VTE treatment: Weight-based dosing (80 units/kg bolus followed by 18 units/kg/h infusion) is recommended 1
  • For acute coronary syndromes: Lower doses are recommended (60-70 units/kg bolus, maximum 5,000 units) 1, 4

• Reversal properties: The relatively short half-life of heparin is advantageous in situations where rapid reversal of anticoagulation may be needed 1

Comparison to Other Anticoagulants

In contrast to UFH's short half-life:

• Low molecular weight heparins (LMWHs) have longer half-lives of 3-6 hours after subcutaneous injection 1
• Fondaparinux has a half-life of 15-20 hours 1

The short half-life of unfractionated heparin makes it particularly useful in situations requiring rapid onset and offset of anticoagulation, such as procedures or in patients with high bleeding risk.