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From Greek: hepar - liver
German: Heparin

1 Definition

Heparin is defined as a group of endogenuous glycosaminoglycans which have an inhibitory effect on the coagulation cascade and, then, are put to therapeutical use as anticoagulants.

2 Structure

Heparin molecules consist of usually unbranched chains of sulphated saccharid blocks that above all contain glucosamine, glucuronic acid and iduronic acid. They are characterized by different molecular weights between 4,000 and 50,000 Dalton. The average weight of heparin is 16,000.

Due to the many carboxyl and sulphate rests in the molecule, heparin is highly negatively charged. Thatís why it forms complexes with alkaline proteins under physiological conditions, eg. With its antagonist protamine.

3 Prevalence

In animal organisms, heparin is foremost present together with histamine in the metachromatic vesicles of mast cell, from where it is secreted in the course of inflammatory reactions amongst others.

4 Function

Heparin binds to various antithrombin molecules, especially antithrombin III, the resulting complex is called immediate inhibitor. It is able to bind the clotting factors II, IX, X and XII, and thereby to prevent their effects.

Moreover, the heparin-antithrombin-complex also inhibits the protease kallikrein and the effect of the membrane attack complex of the complement system.

5 Pharmacology

Heparin has two forms of use in medical therapy, as high-molecular and low-molecular preparation. Frequently, it is isolated from the lungs or intestines of cattle or pigs, and modified if necessary.

The administration of heparin serves the prophylaxis and therapy of coagulation disorders, especially of thrombosis and embolisms.

5.1 High-molecular heparin

High-molecular of unfractioned heparins (UFH) are extracted from animal tissues (above all intestinal pig mucosa), and they have an average molecular mass of 16,000 Dalton. You have to monitor therapy with high-molecular heparins closely by determining coagulation lab values (eg. PTT) in the blood.

Due to its short half-life period, unfractioned heparin is administered for continuous intravenous therapy via a perfusor system (so-called complete heparinization). For prophylaxis, it is applied by s.c. injections three times a day. This is often called low-dose heparinization. Unfractioned heparin is foremost applied in patients with kidney failure.

An overdose of heparin can be antagonized by antagonists such as protamine.

5.2 Fractioned heparin

In contrast to high-molecular heparin, fractioned low-molecular heparin (LMH or LMWH) is fractioned down to an average molecular weight of app. 5,000 Dalton after its isolation from the tissue. It takes effect as a fragment especially by blocking the activated clotting factor X (FXa, Stuart-Prower-Factor).

In contrast to high-molecular heparins, therapy with low-molecular heparin does not have to be monitored closely. PTT is not suitable for controlling therapy, since low-molecular heparins do extend PTT just a little, or not at all. You can control therapy by measuring anti-factor Xa-activity. Protamine also serves as antidote against LMH. Aside from its easier handling (s.c. Injection), higher bioavailability, and longer half-life period, the risk for the development of HIT under LMH therapy is significantly lower.

6 Side effects

The administration of heparin usually is well tolerated and is applied for the treatment of most hospital patients for prophylaxis of thrombosis. Occasionally, heparin-induced thrombocytopaenia (type I or II) occurs. This is potentially lethal. Especially the high-molecular heparin causes a decrease of the platelet count in 5% of cases, whereas this same phenomenon occurs in less than 1% of cases in treatment with fractioned heparin.

Further side effects of heparin therapy comprise an elevated bleeding tendency, hair loss, and, in long-time application, osteoporosis.

In case there are severe side effects, sometimes treatment with another anticoagulants is an option, eg. with hirudin or coumarine derivatives.

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