View source for Antithrombotics

{{Drugclass
|title =
|ATC = B01 Antithrombotic agents
|indications = test
|prototype = [[acetylsalicylic acid]], [[warfarin]], [[heparin]], [[rivaroxaban]]
|param4 = 
|param5 = 
}}

'''Antithrombotics''' are a [[drug class]] that reduce the formation of [[thrombosis|thrombi]] ("blood clots") in the [[circulatory system]].

== Definition ==

== Background ==
The physiological process of '''[[hemostasis]]''' (Greek, ''haima'', "blood" + ''stasis'', "to halt") prevents blood loss when a vessel is damaged. Hemostasis happens by four mechanisms:

* '''Vascular constriction''': smooth muscle in vessel wall contracts.
* '''Thrombocyte aggregation''' ('''primary hemostasis'''): thrombocytes (platelets) clump together and make a platelet plug. This is the part of hemostasis that '''antiplatelet drugs''' inhibit.
* '''Blood coagulation''' ('''secondary hemostasis'''): substances from several sources (damaged vascular wall, platelets, blood proteins) initiate a complex process ('''coagulation cascade''') that results in a complex of activated substances called ''prothrombin activator''. Protrombin activator in turn catalyzes conversion of prothrombin to thrombin. Thrombin converts fibrinogen to fibrin fibers that traps the platelet plug, blood cells and plasma to form the end result of coagulation: a '''thrombus''' (sometimes called '''blood clot''', but technically a thrombus refers to the ''in vivo'' process, and clot to ''in vitro'' event). Coagulation is sometimes called '''clotting'''. '''Anticoagulants''' act by preventing fibrin formation.
* After thrombus formation, the thrombus can either be invaded by fibroblasts ('''fibrous organization''') or dissolve (via '''fibrinolysis''').

Factors that promote coagulation process are '''prothrombotic''', and those that oppose it are '''antithrombotic'''. An excess of procoagulant factors, and a lack of anticoagulant factors, leads to thrombosis; conversely, an excess of anticoagulant factors, or a loss of procoagulant factors, leads to bleeding. Coagulation has certain steps that catalyze themselves further (positive feedback), but in a homeostatic state the coagulation process is kept local, otherwise it would quickly coagulate all blood in the circulation. A "hemostatic" plug in non-bleeding vasculature is called '''thrombosis''' ("hemostasis in the wrong place"). Underlying the formation of thromboses is three mechanisms, sometimes called '''Virchow's triad''':

* '''Endothelial injury''': roughened endothelial surface of a vessel can initiate the clotting process, e.g. in [[atherosclerosis]], infection, trauma, biomaterial implants (e.g., artificial heart valves).
* '''Stasis''': blood clots more frequently when it flows slowly through vessels, since procoagulants (including thrombin) accumulate, e.g. [[atrial fibrillation]], [[heart failure]], immobility when driving, flying, in surgery.
* '''Hypercoagulability''': changes to the blood's composition, e.g. in deficiencies in antithrombin III, protein C or S; coagulation factor V Leiden mutation; [[cancer]], hormonal contraceptives, obesity, dehydration.

There are two types of thrombi: red and white.

{| class="wikitable" 
|-
! 
! Red thrombus
! White thrombus
|-
| Blood vessel
| Venous
| Arterial
|-
| Location
| Normal vessels, generally deep legs of vein and cerebral sinus.
| Coronary and cerebral circulation. Often superimposed on atheroma.
|-
| Composition
| Erytrocytes in fibrin mesh, erytrocytes give reddish appearance.
| Platelets, give grey-white appearance.
|-
| Mechanism
| Low-pressure system. Stasis, hypocoagulability.
| High-pressure system. Turbulent blood flow.
|-
| Diseases
| DVT, LE, AF
| MI, stroke
|-
| Treatment
| Anticoagulant drugs
| Antiplatelet drugs
|}

The '''[[coagulation cascade]]''' is central to blood coagulation. To understand anticoagulants, the coagulation cascade must be understood.
Coagulation works by a number of subsequent reactions, where inactive coagulation ''factors'' (mostly enzyme precursors) are activated and catalyze the next reaction in the cascade. The final goal of coagulation, as described above, is the formation of fibrin. Each coagulation factor (''F'') is indicated by Roman numerals, and the active factors are denoted by "''a''".
The classical way of considering the coagulation cascade is that there are two pathways that lead to fibrin formation:

* '''Extrinsic pathway''' ('''tissue factor pathway''') know as the ''extrinsic'' pathway because tissue factor, which is necessary to initiate the pathway, is not normally present in the blood and thus extrinsic to it, must be added. FXII &rarr; FXI &rarr; FIX &rarr; FVIIIa &rarr; FX.
* '''Intrinsic pathway''' ('''contact activation pathway'''): the necessary element, thrombin (FIII), is present in (and thus ''intrinsic'' to) the blood. FVII &rarr; FX.

Both pathways lead to the '''final common pathway''': FXa &rarr; FV &rarr; prothrombin (FII) &rarr; thrombin (FIIa) &rarr; fibrinogen (FI) &rarr; fibrin (FIa) &rarr; cross-linked fibrin clot.

== Antithrombotic drug types ==
Antithrombotics can be divided into three groups:
* '''Antiplatelet drugs'''
* '''Anticoagulant drugs'''
* '''Thrombolytic drugs'''

=== Antiplatelet drugs ===

=== Anticoagulant drugs ===

== Functional assessment ==
=== Common ===
PT, aPTT.

=== Specialized ===
Multiplate, ROTEM/TEG, thrombodynamics.

== History ==

[[Category:Pharmacology]]