From the Guidelines
Unfractionated heparin is primarily cleared by the reticuloendothelial system in the liver, not by the kidneys, with only a small proportion, approximately 10-20%, being excreted renally. This is supported by the most recent and highest quality study, which highlights the importance of considering the pharmacokinetics of anticoagulants in patients with renal impairment 1. The hepatic clearance of unfractionated heparin occurs through a saturable, dose-dependent mechanism involving binding to endothelial cells, macrophages, and proteins, where it is depolymerized and metabolized.
Some key points to consider when using unfractionated heparin include:
- The liver is the primary site of heparin biotransformation, making it a preferred choice in patients with severe renal impairment or kidney failure 2, 1
- Unfractionated heparin requires more frequent monitoring through activated partial thromboplastin time (aPTT) due to its variable pharmacokinetics 3, 1
- In contrast, low molecular weight heparins (LMWHs) like enoxaparin are significantly eliminated by the kidneys (40-60%) and require dose adjustments in renal impairment 4
The non-renal clearance pathway of unfractionated heparin makes its dosing more predictable in renal dysfunction. However, it is essential to carefully select treatment methods that balance efficacy and safety, especially in patients with cancer 1. Overall, the use of unfractionated heparin should be guided by its pharmacokinetic properties and the individual patient's clinical characteristics.
From the FDA Drug Label
Heparin is mainly cleared from the circulation by liver and reticuloendothelial cells mediated uptake into extravascular space Heparin undergoes biphasic clearance, a) rapid saturable clearance (zero order process due to binding to proteins, endothelial cells and macrophage) and b) slower first order elimination.
No, unfractionated heparin is not primarily renally excreted. The drug label indicates that heparin is mainly cleared from the circulation by the liver and reticuloendothelial cells, with no direct mention of renal excretion as a primary mechanism of elimination 5.
From the Research
Unfractionated Heparin Excretion
- Unfractionated heparin is removed from the blood via two mechanisms: saturable and non-saturable 6
- The non-saturable mechanism represents renal excretion, which contributes to the clearance of unfractionated heparin, especially at higher doses 6
- However, unfractionated heparin generally does not require dose adjustment with renal dysfunction, according to some studies 7, 8
- It is worth noting that the pharmacokinetic properties of unfractionated heparin can be unpredictable, and its use in patients with severe renal impairment may require close monitoring 8, 9
Comparison with Low-Molecular-Weight Heparin
- Low-molecular-weight heparins are mainly removed by non-saturable renal excretion, which can lead to bioaccumulation in patients with renal insufficiency 9, 6
- In contrast, unfractionated heparin has a more complex clearance mechanism, involving both saturable and non-saturable pathways 6
- Some studies suggest that low-molecular-weight heparins, such as tinzaparin, may be easier to manage than unfractionated heparin in patients with severe renal impairment 10