Duration of Heparin's Anticoagulant Effect
The anticoagulant effect of intravenous heparin lasts approximately 60-90 minutes after discontinuation, with a half-life of 60-90 minutes, while subcutaneous heparin's effect is delayed by 1-2 hours and peaks at 3 hours after administration. 1
Pharmacokinetics of Heparin
Intravenous Administration
- Half-life: 60-90 minutes (varies with dose)
- At low doses (25 units/kg): ~30 minutes
- At standard therapeutic doses (100 units/kg): ~60 minutes
- At high doses (400 units/kg): ~150 minutes 1
- Onset of action: Immediate
- Duration of effect: Effects diminish within 60-90 minutes after stopping infusion
Subcutaneous Administration
- Onset of action: Delayed for 1-2 hours
- Peak effect: Occurs approximately 3 hours after injection
- Bioavailability:
- Low doses (5,000 units q12h): Reduced plasma recovery
- High therapeutic doses (>35,000 units/24h): Almost complete plasma recovery 1
Factors Affecting Heparin Duration
Clearance Mechanisms
Heparin is cleared through two primary mechanisms:
Rapid saturable mechanism:
- Binding to endothelial cell receptors and macrophages
- Dose-dependent and predominant at therapeutic doses
- Results in depolymerization of the heparin molecule
Slower first-order mechanism:
- Primarily renal clearance
- Becomes more important at very high doses 1
Patient-Specific Factors
- Pulmonary embolism: Significantly shortened half-life (demonstrated in studies showing half-life of ~63 minutes in most patients vs. significantly shorter in those with PE) 2
- Weight: Affects volume of distribution and clearance
- Renal function: Impacts the slower clearance mechanism
- Binding proteins: Variable levels of heparin-binding proteins affect anticoagulant response 1
Clinical Implications
Monitoring Requirements
- First aPTT measurement: 6 hours after bolus dose
- Subsequent monitoring:
Transitioning Between Anticoagulants
- When transitioning to oral anticoagulants:
- Allow at least 5 hours after the last IV heparin dose before drawing blood for prothrombin time
- Allow 24 hours after the last subcutaneous dose 4
- Overlap with warfarin for 4-5 days until INR is therapeutic (2.0-3.0) for 2 consecutive days 3
Common Pitfalls
- Inadequate monitoring: Failure to achieve therapeutic aPTT within 24 hours is associated with increased risk of recurrent thromboembolism
- Rebound effect: Abrupt discontinuation may lead to rebound hypercoagulability in some patients
- Variable response: Inter-individual variations in heparin clearance and response necessitate individualized monitoring
- Drug interactions: Medications like nitroglycerin can decrease aPTT with subsequent rebound upon discontinuation 4
Remember that the pharmacokinetics of heparin are nonlinear at therapeutic doses, with both intensity and duration of effect rising disproportionately with increasing doses due to the saturable clearance mechanism 1.