Heparin aldosterone inhibition

Heparin-induced hypoaldosteronism is well documented, both in patients treated with standard heparin, even at low doses, and in patients treated with low molecular weight heparin (477,478). The most important mechanism of aldosterone inhibition appears to be a reduction in both the number and affinity of angiotensin II receptors in the zona glomerulosa (477). A direct effect of heparin on aldosterone synthesis, with inhibition of conversion of corticosterone to 18-hydroxycorticosterone, has also been suggested. This effect is believed to be responsible for the hyperkalemia that can occur in heparin-treated patients with impaired renal function and particularly in patients on chronic hemodialysis (479), or with diabetes mellitus, or who are taking other potentially hyperkalemic drugs. 

Heparin acts as a catalyst for antithrombin III (AT III), increasing its activity by approximately a thousand times. Antithrombin III is a plasma enzyme that inactivates certain activated serine proteases of the coagulation cascade, most importantly activated factors II (thrombin) and X. The larger heparin species (found in unfractionated heparin) catalyzes the inactivation of activated factors II and X. In contrast, LMWH chiefly inactivates activated factor X. The final effect of both is systemic anticoagulation. Heparin also possesses inherent platelet-aggregating properties and may also induce the production of platelet-aggregating antibodies. Heparin can inhibit aldosterone synthesis. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS ANTICOAGULANTS -PARENTERAL T risk of hyperkalaemia with heparins Heparin inhibits aldosterone secretion, causing hyperkalaemia Monitor potassium levels closely... 

HEPARINS ANALESICS - NSAIDs 1. Risk of prolonged bleeding when ketorolac is co-administered with dalteparin (but not enoxaparin), and intravenous diclofenac is given with heparins 2. t risk of hyperkalaemia when ketorolac is given with heparin 1. Uncertain 2. Heparin inhibits aldosterone secretion, causing hyperkalaemia 1. Avoid co-administration 2. Monitor potassium levels closely... 

Two forms of heparin-induced thrombocytopenia (HIT) have been observed. The first (HIT I) is a transient, mild, and benign thrombocytopenia seen soon after initiation of heparin therapy (normally within 2 days) and is felt to be due to inherent plateletaggregating properties of heparin. A second, more severe form of HIT (HIT II) is typically seen later and is immune-mediated. The incidence of HIT II is estimated at 3-5%. The onset is generally 3-14 days after initiation of heparin therapy but may occur sooner with repeat exposure. HIT II may occur with any dose and type of heparin, but the frequency is highest with continuous intravenous infusions of unfractionated heparin. HIT with subsequent thrombosis is a feared complication. These thrombi can form in the venous or arterial circulation. Thrombotic complications include necrotic skin lesions, myocardial infarction, stroke, and gangrene. Hyperkalemia may be seen with heparin therapy due to aldosterone synthesis inhibition. 

The subject of the present review stems from the discoveries of A. Fischer and E. Jorpes. Fischer demonstrated that heparin binds or complexes with proteins and other bases and so modifies their biological activity. As a result, heparin is able to release or activate enzymes such as lipoprotein lipase -, to inhibit hormones such as cortisone and aldosterone , to detoxify toxic agents, and to bind histamine in body cells . Jorpes discovered that heparin is a highly sulphated polysaccharide and that it gives a specific colour reaction with dyes the metachromatic reaction. This resulted in (i) the association of heparin with the naturally occurring mucopolysaccharides ... 

Heparin is known to inhibit aldosterone synthesis. This is not considered clinically significant. However the effects on aldosterone may lead to hyperkalemia and metabolic abnormalities with long term therapy. 

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