Anticoagulants

Anticoagulants are drugs that reduce blood clotting. By their action, they block coagulation factors, and thus coagulation itself (in layman's terms, "blood thinning" is referred to). They are mainly used for the prophylaxis of venous and intracardiac thrombosis and subsequent embolism. They are used in the laboratory as anticoagulants.

The ideal anticoagulant should:


 * be applicable p.o. parenterally;
 * have a rapid onset of action;
 * have predictable properties and therefore fixed dosing;
 * be safe;
 * have an antidote available;
 * be free from interactions with other drugs or foods.

Classification
File: Schema coagulation.png Anticoagulants can be divided into substances used in vivo (patient) and substances used in vitro (laboratory).

Furthermore, anticoagulants can be divided into direct and indirect according to their mechanism of action. Direct anticoagulants inactivate the coagulation factors themselves present in plasma, while indirect anticoagulants affect coagulation factors by reducing their production in the liver.

Direct anticoagulants
Direct anticoagulants block mainly thrombin and / or factor Xa. Thrombin is a key protein in the coagulation cascade that activates a number of coagulation factors and, in particular, catalyzes the conversion of fibrinogen to insoluble fibrin.


 * Indirect thrombin / factor Xa inhibitors act by activating the natural thrombin inhibitor - antithrombin (AT III). They are therefore dependent on the presence of endogenous inhibitors. This is how heparins, for example, work.
 * Direct thrombin / factor Xa inhibitors bind to thrombin or factor Xa and thereby block their function. These include xabans, gatrans and hirudins.

Heparin and its derivatives
link=https://www.wikiskripta.eu/w/Soubor:Heparin-2D-skeletal.png|right|thumb|Chemical formula of part of the heparin chain link=https://www.wikiskripta.eu/w/Soubor:Antikoag_nizkomol.png|right|thumb|Effects of high molecular weight and low molecular weight heparin Heparin is a mixture of acidic mucopolysaccharides commonly found in the body. Unfractionated heparin, low molecular weight and pentasaccharides are used therapeutically.

link=https://www.wikiskripta.eu/w/Soubor:Antikoag_nizkomol.png|right|thumb|Effects of high molecular weight and low molecular weight heparin Unfractionated (natural) heparin activates AT III, which irreversibly inactivates thrombin and some other coagulation factors (eg factor Xa). It has the following features:


 * does not cross the placenta and is therefore suitable for use in pregnancy;
 * has a specific antidote - protamine,

but


 * poorly absorbed, administered i.v. (in s.c. application, the effect begins after about 2 hours);
 * it has a short-term effect and has variable biodegradation, therefore APTT should be checked regularly after 6 hours;
 * may induce thrombocytopenia (immune mechanism?).

Side effects: bleeding, allergic reaction, osteoporosis (long-term use).

Low molecular weight heparins
Low molecular weight heparins (LMWH) have shorter chains formed by the breakdown of heparin. They act similarly to unfractionated heparin (but inactivate mainly factor Xa), but they are safer, have a better anticoagulant effect, fewer side effects and more favorable pharmacokinetics. Low molecular weight heparins:


 * are better absorbed, applied s.c. (mostly in the abdomen);
 * have a longer effect;
 * have a lower risk of induced thrombocytopenia;
 * does not need to be checked by APTT,

but


 * are sparingly neutralizable by protamine
 * and have prescription restrictions in renal insufficiency (GFR <50 ml / min)

In practice, enoxaparin in particular is used.

Indications: prevention and treatment of thrombosis.

Contraindications: bleeding conditions.

Must not be given i.m. due to the risk of severe muscle bleeding.

A cheaper option with similar properties is bemiparin, but there are not enough studies.

Související články

 * Prothromplex
 * Heparin
 * Warfarin
 * Fibrinolytika
 * Hemokoagulace
 * Cirkulující antikoagulancia
 * Trombóza
 * Vyšetření krvácivosti
 * Vyšetření krevní srážlivosti

Zdroj

 * BULTAS, Jan. Kurz Farmakoterapie kardiovaskulárních chorob. 3. LF UK, 2010.