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 an IV bolus of 25 units/kg to 60 minutes with 100 units/kg, and up to 150 minutes with 400 units/kg. 1

Pharmacokinetics of Unfractionated Heparin

Unfractionated heparin (UFH) demonstrates complex pharmacokinetics with several important characteristics:

Dose-Dependent Half-Life

• The half-life increases disproportionately with increasing doses due to its complex clearance mechanisms:
  • At low doses (25 units/kg IV): ~30 minutes
  • At moderate doses (100 units/kg IV): ~60 minutes
  • At high doses (400 units/kg IV): ~150 minutes 1

Clearance Mechanisms

Heparin is cleared through two primary mechanisms:

1. Rapid saturable phase:

   • Involves binding to endothelial cell receptors and macrophages
   • Heparin is internalized and depolymerized
   • This is the predominant clearance mechanism at therapeutic doses

2. Slower non-saturable phase:

   • Primarily renal clearance
   • First-order elimination kinetics 1

Distribution

• After entering the bloodstream, heparin binds to:
  • Antithrombin (its primary target)
  • Other plasma proteins (fibrinogen, albumin, etc.)
  • Endothelial cells and macrophages
  • Von Willebrand factor 1
• Volume of distribution is generally limited to plasma volume 2

Clinical Implications

Monitoring and Dosing

• The non-linear pharmacokinetics of heparin necessitate careful monitoring
• Therapeutic dosing requires consideration of the dose-dependent half-life
• Weight-based dosing protocols are more effective than fixed-dose regimens 1

Special Populations

• Elderly patients (>60 years): May have higher plasma levels and longer aPTTs compared to younger patients with similar dosing 3
• Renal impairment: May have moderately prolonged heparin half-life 4

Common Pitfalls

• Failure to recognize dose-dependency: The same dose of heparin may produce different effects as clearance mechanisms become saturated
• Inadequate initial dosing: Subtherapeutic initial dosing is associated with higher rates of recurrent thromboembolism 1
• Monitoring confusion: Different methods of measuring heparin effect (anti-Xa activity vs. aPTT) may yield different apparent half-lives 5

Comparison with Low Molecular Weight Heparins

Unlike unfractionated heparin, LMWHs have:

• Longer half-lives (3-6 hours)
• More predictable dose-response
• Primarily renal clearance
• Dose-independent elimination 1

The complex pharmacokinetics of unfractionated heparin make its clinical use more challenging than LMWHs, but its short half-life can be advantageous in situations requiring rapid reversal of anticoagulation.