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

Dose-Dependent Half-Life

• At therapeutic doses, the average half-life is typically between 60-90 minutes 1, 2
• The FDA label confirms that plasma half-life ranges from 0.5 to 2 hours and is dose-dependent 2
• Studies have shown specific half-life measurements:
  • 63 ± 15 minutes when measured by plasma heparin activity 3
  • 84 ± 71.5 minutes when measured using activated partial thromboplastin time (APTT) 3

Clearance Mechanisms

Heparin undergoes biphasic clearance through two primary mechanisms 2:

1. Rapid saturable clearance: Zero-order process due to binding to proteins, endothelial cells, and macrophages
2. Slower first-order elimination: Less dominant at therapeutic doses

Distribution

• Heparin is highly bound to antithrombin, fibrinogens, globulins, serum proteases, and lipoproteins 2
• Volume of distribution is limited to plasma volume (approximately 0.07 L/kg) 2, 4

Factors Affecting Heparin Half-Life

Patient-Specific Factors

• Age: Patients over 60 years may have higher plasma levels and longer aPTTs compared to younger patients 2
• Renal function: Impaired renal function can moderately prolong heparin half-life (up to 118.6 minutes in nephrectomized patients vs. 74.7 minutes in normal subjects) 5
• Pulmonary embolism: May significantly shorten heparin half-life 3

Measurement Method

The method used to measure heparin activity affects the calculated half-life:

• Chemical neutralization methods yield different values than coagulation-based tests 6
• Values for clearance and volume of distribution based on chemical neutralization are approximately 1.5-2.0 times higher than those based on coagulation tests 6

Clinical Implications

• The short half-life necessitates continuous infusion for maintaining therapeutic anticoagulation 1
• Rapid clearance allows for quick reversal of anticoagulant effect when stopped 1
• Regular monitoring is essential due to variable patient response 1
• Weight-based dosing provides more predictable anticoagulation than fixed dosing 1

Comparison with Other Anticoagulants

• Low Molecular Weight Heparins: Have longer half-lives (3-6 hours), allowing for once or twice daily dosing 1
• Direct Thrombin Inhibitors: Argatroban has a half-life of approximately 50 minutes but may be prolonged in patients with hepatic dysfunction 7, 8
• Bivalirudin: Has a short half-life of 15-30 minutes 7

The short half-life of unfractionated heparin makes it particularly useful in situations requiring rapid anticoagulation with the ability to quickly reverse effects, such as during surgical procedures or in patients at high bleeding risk.