Heparin

Mucopolysaccharide formed in mast cells that inhibits blood clotting and promotes fibrinolysis. Herapin potentiates the effect of antithrombin.

Rosenberg was able to clarify the mode of action of heparin in 1973. Heparin binds to lysine residues of antithrombin III (ATIII) to form the heparin-AT complex. This leads to a conformational change in the active centre of AT-III. As a result, antithrombin III is converted from a slow-acting to a fast-acting inhibitor of the coagulation factors and the AT-III effect is multiplied thousandfold. Heparin dissociates after this action of the heparin-AT complex and becomes active again.
The heparin-AT complex inhibits thrombin and factor Xa.

Furthermore, the heparin-AT complex inhibits the serine proteases by inhibiting their proteolytic activity and thus the blood coagulation cascade of the intrisic system.

Another effect of high molecular weight heparin is the inhibition of platelet function and vasodilation. On the other hand, the platelets inhibit the anticoagulant effect of heparin by binding factor Xa, which is thus protected from the heparin-AT-III complex, and by secreting heparin-neutralizing platelet factor 4
.Other anticoagulant effects of heparin are its effects on endothelial cells. Here, unfractionated and low-molecular-weight heparin activates the synthesis of the anticoagulant, heparin-like heparan sulfate and stimulates the release of the tissue factor pathway inhibitor (TFPI).

Furthermore, heparin enhances fibrinolytic activity by stimulating the release of t-PA (tissue plasminogen activator) from the endothelium. Heparin binds to plasma and platelet proteins such as platelet factor 4, fibronectin, thrombospondin, complement and beta-thromboglobulin.
In addition, heparin has a number of functions that are not directly related to clotting. For example, it acts on a lipoprotein lipase in the endothelium and intervenes in triglyceride metabolism.

In the defence against allergic and anaphylactic conditions, it is detectable in high concentrations in mast cells and is released from these in allergic reactions, thus exercising a protective function for the organism.
Heparin antagonizes the toxicity of substances that release histamine. Heparin is broken down by a heparinase that is detectable in the liver and kidney.

Therapeutic application is heparin as a fast-acting anticoagulant for the prevention and treatment of thromboses and embolisms. Commercially available are heparins with a molecular weight between 4,000 daltons (low molecular weight heparin; fractionated) and 50,000 daltons (high molecular weight heparin; non-fractionated) for s.c. and i.v. injection. Antagonist for heparins is e.g. protamine hydrochloride. S.u. heparins, systemic, see below Heparins, topical, see below Heparinoids, systemic, see below Heparinoids, topical.

• Bleeding (dose-dependent general bleeding risk)
• Reversible increase of transaminases (often in 60% of cases)
• Allergic reactions (see below heparin allergy)
• Hypersensitivity reactions (urticaria, rhinitis, conjunctivitis, bronchospasm)
• thrombocytopenia
• diffuse hair loss
• (Localized) skin necroses (rare; especially occurring 5-9 days after the start of therapy at the injection sites of subcutaneous injections).
• Osteoporosis (especially with long-term use).

Essaven® Gel, Venalot® Liniment, Venoplant® Gel

The monitoring of therapy with unfractionated heparin is performed by the thrombin time or by the activated partial thrombin time (aPTT).