Anticoagulation Therapy with Heparin

Pharmacokinetics

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, 2
Half-life of intravenous heparin varies with dose: ~30 minutes at low doses (25 units/kg), ~60 minutes at standard therapeutic doses (100 units/kg), and ~150 minutes at high doses (400 units/kg) 2
Bioavailability of subcutaneous heparin is reduced at low doses (5,000 units q12h) but almost complete at high therapeutic doses (>35,000 units/24h) 1, 3
Heparin is cleared through two primary mechanisms: a rapid saturable mechanism and a slower first-order mechanism, with the latter being primarily renal clearance 2, 3

First aPTT measurement should be taken 6 hours after bolus dose, with subsequent monitoring every 4-6 hours after dose changes and daily once stable 1, 4
When transitioning to oral anticoagulants, allow at least 5 hours after the last IV heparin dose before drawing blood for prothrombin time 4
Overlap with warfarin for 4-5 days until INR is therapeutic (2.0-3.0) for 2 consecutive days 4

Inadequate monitoring can lead to increased risk of recurrent thromboembolism, and variable response to heparin necessitates individualized monitoring 4
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 2, 3