What is the half-life of heparin (unfractionated heparin) injectable in a patient with normal renal function?

Half-Life of Injectable Unfractionated Heparin

The half-life of unfractionated heparin is dose-dependent and nonlinear, ranging from approximately 30 minutes at low doses (25 units/kg IV bolus) to 60 minutes at standard therapeutic doses (100 units/kg IV bolus), and up to 150 minutes at high doses (400 units/kg IV bolus) in patients with normal renal function. 1, 2

Dose-Dependent Pharmacokinetics

The half-life increases disproportionately with dose due to heparin's complex clearance mechanisms:

• At 25 units/kg IV bolus: approximately 30 minutes 1, 2
• At 100 units/kg IV bolus: approximately 60 minutes 1, 2
• At 400 units/kg IV bolus: up to 150 minutes 1, 2

The FDA label simplifies this for clinical reversal purposes, stating that heparin may be assumed to have a half-life of about 30 minutes after intravenous injection when calculating protamine doses. 3

Mechanism of Nonlinear Clearance

Heparin is cleared through two distinct pathways: a rapid saturable mechanism (predominant at therapeutic doses) and a slower first-order renal mechanism. 1, 2

• The rapid saturable phase involves binding to endothelial cell receptors and macrophages, where heparin is internalized and depolymerized 1
• At therapeutic doses, the saturable mechanism handles the majority of clearance, causing the nonlinear pharmacokinetics 1, 2
• This means doubling the heparin dose more than doubles both the intensity and duration of anticoagulant effect 1, 2

Clinical Implications for Normal Renal Function

The American College of Chest Physicians recommends monitoring aPTT during therapeutic anticoagulation due to the variable and dose-dependent half-life of unfractionated heparin. 2

• The complex kinetics render the anticoagulant response unpredictable, with significant inter-patient variability 1
• Heparin binds to multiple plasma proteins beyond antithrombin, reducing bioavailability and contributing to variable responses 1

Important Caveats

While renal function has minimal impact on heparin clearance in normal kidneys (since the saturable mechanism predominates), severe renal impairment can moderately prolong the half-life. Research shows heparin concentration half-life increases from 74.7 minutes in normal patients to 97.8-118.6 minutes in uremic patients, though this effect is modest compared to the dose-dependent variability. 4

Hepatic dysfunction significantly affects heparin metabolism, with cirrhotic patients showing mean half-lives of 117.8 minutes compared to 74.0 minutes in normal patients, as the liver appears to metabolize heparin-antithrombin complexes. 5