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 of 25 units/kg to 60 minutes with 100 units/kg, and up to 150 minutes with higher doses of 400 units/kg. 1

Pharmacokinetic Properties of Unfractionated Heparin

Unfractionated heparin (UFH) exhibits complex pharmacokinetics characterized by:

• Dose-dependent half-life: The half-life increases with higher doses due to saturable clearance mechanisms
• Route-dependent bioavailability:
  • IV administration: 100% bioavailability with immediate onset of action 2
  • Subcutaneous administration: Reduced bioavailability, especially at lower doses 1

Clearance Mechanisms

Heparin is cleared through two primary mechanisms:

1. Rapid saturable clearance (zero-order process):

   • Binding to endothelial cell receptors and macrophages
   • Internalization and depolymerization
   • Predominant at therapeutic doses

2. Slower first-order elimination:

   • Primarily renal clearance
   • Less significant at standard therapeutic doses 2

Factors Affecting Heparin Half-Life

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

• Dose: Higher doses lead to disproportionately longer half-lives 1
• Age: Patients over 60 years may have higher plasma levels and longer aPTT times with standard doses 2
• Renal function: Impaired renal function can moderately prolong heparin half-life 3
• Binding proteins: Heparin binds to multiple plasma proteins (antithrombin, fibrinogen, albumin) affecting its availability 4
• Individual variability: Significant inter-patient variability in clearance and response 5

Clinical Implications

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

• Continuous infusion: Required for maintaining therapeutic anticoagulation due to short half-life
• Monitoring: Regular aPTT monitoring needed due to variable response
• Reversal: Rapid clearance allows for quick reversal of anticoagulant effect when stopped
• Dosing strategy: Weight-based dosing provides more predictable anticoagulation than fixed dosing 1

Comparison with Other Anticoagulants

In contrast to UFH, low molecular weight heparins (LMWHs) have:

• Longer half-life (3-6 hours) allowing once or twice daily dosing 1
• More predictable anticoagulant response
• Higher bioavailability after subcutaneous administration (approximately 90%)
• Less binding to plasma proteins and cells 1

Common Pitfalls

• Measurement variability: Different assay methods can yield different half-life values, ranging from 23 minutes to 2.48 hours 6
• Underdosing: Inadequate initial dosing can lead to treatment failure in VTE
• Monitoring confusion: Differentiating between concentration half-life and anticoagulant effect half-life 6
• Route of administration: Subcutaneous administration requires higher doses to achieve therapeutic effect compared to IV administration 1, 7

Understanding heparin's variable and dose-dependent half-life is essential for appropriate dosing and monitoring to ensure both efficacy and safety in clinical practice.