Heparins low-molecular

A further development of classical heparin is fractionated heparin with chain lengths corresponding to a molecular weight of 4000 to 6000 D. This heparin is called low-molecular-weight (LMW) heparin. These are fractions or fragments of heparin from pig intestinal mucosa or bovine lung.
The individual low-molecular-weight heparins differ in their molecular size and activity, so that there is a separate dosage regulation for each low-molecular-weight heparin. NMW heparins are obtained enzymatically from unfractionated heparin with heparinase or by cleavage with isocyanyl nitrite.
In contrast to non-fractionated heparin, the low-molecular-weight heparins bind only to antithrombin III via the pentasaccharide structures and thus act predominantly by inhibiting factor Xa. The molecules of unfractionated heparin contain only 8-14 monosaccharides, so that the effect of low-molecular-weight heparins on antithrombin is significantly lower than that of unfractionated heparins. The ratio of antifactor Xa to antifactor IIa is 2-4:1 for low-molecular-weight heparin and 1:1 for unfractionated heparin.

Low molecular weight heparins, similar to unfractionated heparin, stimulate endothelial heparan synthesis and release TFPI from the endothelium. Compared to heparin, the bioavailability is significantly higher, at approx. 90%. Heparins are not placental and can be given in both forms, unfractionated and fractionated, during pregnancy.

In clinical application, especially in postoperative prophylaxis or in the therapy of venous thrombosis, the fractionated and unfractionated heparins are identical in their effect. However, the low-molecular-weight heparins only need to be administered once a day in comparison to the high-molecular-weight ones. The main advantage of low-molecular-weight heparin is that HIT-2 occurs significantly less frequently. Higher doses of heparin are generally required in feverish conditions than at normal body temperature.
Protamine acts as an antidote for heparin therapy. To neutralize 100 units of heparin, 1 mg protamine is needed. Antagonists of heparin are polylysine and platelet factor 4. The risk of bleeding under heparin therapy is 4-6%. Allergies are extremely rare.

Heparin is practically not absorbed in the intestine and is therefore administered subcutaneously. Its bioavailability is 30%.
The monitoring of the therapy with low-molecular-weight heparin is carried out by the anti-F-Xa test or by the Pefakit test (PiCT = prothrombinase-included clotting time). This is a coagulometric test. Another possibility is the use of chromogenic substrates, whereby the substrate is usually associated with p-nitroaniline. The enzymatically released dye is measured photochemically.

Low molecular weight heparins (overview)

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