Unfractionated Heparin Binding to Proteins

Protein Binding Properties of UFH

Unfractionated heparin (UFH) binds extensively to plasma proteins, blood cells, and endothelial cells, which contributes to its variable anticoagulant response and pharmacokinetic profile, as noted by the American Heart Association 1, 2
This protein binding contributes to the variable anticoagulant response observed among patients with thromboembolic disorders and can lead to the laboratory phenomenon known as "heparin resistance", according to the American College of Cardiology 3
UFH also binds to von Willebrand factor, which inhibits von Willebrand factor-dependent platelet function, as reported by the American College of Cardiology 3

UFH is a heterogeneous mixture of polysaccharide chains with molecular weights ranging from 5,000 to 30,000 Daltons, as described by the American Heart Association 1, 2
The remaining two-thirds of UFH molecules bind to other plasma proteins and cellular components, as noted by the American Heart Association 4

The extensive protein binding of UFH results in variable anticoagulant response requiring laboratory monitoring, as recommended by the American College of Cardiology 2
UFH clearance occurs through two mechanisms: a rapid saturable mechanism involving binding to endothelial cells and macrophages, and a slower, first-order mechanism that is primarily renal, as reported by the American College of Cardiology 3
Reduced bioavailability when administered subcutaneously is also a consequence of protein binding, as noted by the American Heart Association 4

LMWHs exhibit decreased binding to plasma proteins and endothelial cells compared to UFH, resulting in a more predictable dose-response relationship, as described by the American College of Cardiology 1, 2
This reduced protein binding of LMWHs results in longer half-life allowing once or twice daily dosing, as recommended by the American Heart Association 2
Less need for laboratory monitoring is also a benefit of LMWHs due to their reduced protein binding, as noted by the American College of Cardiology 5

When administering UFH, clinicians should be aware that initial doses may have reduced effect due to protein binding, as reported by the American College of Cardiology 3
Therapeutic effect can be variable between patients due to differences in protein binding, as noted by the American Heart Association 4
Laboratory monitoring (typically aPTT or anti-factor Xa) is essential to ensure therapeutic anticoagulation, as recommended by the American Society of Anesthesiologists 6
Dosing adjustments are often necessary to maintain therapeutic levels, as described by the American College of Cardiology 2