Half-Life of Unfractionated Heparin
The half-life of unfractionated heparin is dose-dependent and nonlinear, ranging from approximately 30 minutes after a low-dose IV bolus (25 units/kg) to 60 minutes with a standard bolus (100 units/kg), and up to 150 minutes with high-dose administration (400 units/kg). 1
Pharmacokinetic Characteristics
The complex clearance kinetics of heparin make its half-life highly variable and dependent on the administered dose:
- At 25 units/kg IV bolus: Half-life is approximately 30 minutes 1
- At 100 units/kg IV bolus: Half-life extends to approximately 60 minutes 1
- At 400 units/kg IV bolus: Half-life can reach 150 minutes 1
The FDA-approved labeling confirms this dose-dependent plasma half-life ranges from 0.5 to 2 hours 2.
Mechanism of Nonlinear Clearance
Heparin undergoes biphasic clearance through two distinct mechanisms 1, 2:
- Rapid saturable mechanism (zero-order): Binding to endothelial cell receptors and macrophages, where heparin is internalized and depolymerized—this pathway predominates at therapeutic doses 1
- Slower first-order mechanism: Primarily renal clearance, which becomes more relevant at lower doses 1
This dual clearance pathway renders the anticoagulant response nonlinear at therapeutic doses, with both intensity and duration of effect rising disproportionately with increasing dose 1.
Clinical Implications
The dose-dependent half-life has important practical consequences:
- Immediate onset: Peak plasma concentration and anticoagulant effect occur immediately after IV administration 2
- Unpredictable duration: The variable half-life contributes to the need for activated partial thromboplastin time (aPTT) monitoring during therapeutic anticoagulation 1
- Geriatric considerations: Patients over 60 years may have higher plasma levels and longer aPTTs compared to younger patients receiving similar doses 2
Important Caveats
The effective biological half-life increases nonlinearly with dose, meaning doubling the heparin dose more than doubles the duration of anticoagulant effect 1. This nonlinear pharmacokinetic profile explains why heparin requires careful dose titration and monitoring, unlike low-molecular-weight heparins which have predictable, linear pharmacokinetics with half-lives of 3-4 hours regardless of dose 3, 4, 5.