The mechanisms involved to stop bleeding are known as hemostasis. This includes four processes:
- Platelet plug formation
- Coagulation/Clot formation
- Clot becomes fibrous, remains as such, or dissolves
The injury is repaired, limiting blood loss and maintaining the patency of vessels.
This process can go the pathological way either leading to:
- Increased bleeding tendency
- Thromboembolic phenomenon
The blood fluidity is maintained by four factors:
- Circulation –continuous motion. Stasis may lead to coagulation disorders
- Smooth endothelial lining of blood vessels and negatively charged glycocalyx
- Naturally occurring anticoagulants and thrombolytics:
- Thrombomodulin binds endothelial vessels
- Binds thrombin and inactivates it
- Activates natural anticoagulant, protein C
- Presence of antithrombin III in blood, which inactivates many of the clotting factors II, IX, X, XI and XII and to some extent VII.
- Tissue plasminogen activator, released in endothelial injury, acts on plasminogen converting it to plasmin. Plasmin acts on fibrin and breaks it, thus having thrombolytic activity.
Endogenous anticoagulants include:
- Protein C –proteolysis of Va
- Protein S –proteolysis of VIII a
Blood coagulation is maintained by clotting factors, inactive proteins present in the blood, which are activated in cascade manner.
Drugs preventing clotting (pathological thrombosis) by reducing coagubility of blood, are called anticoagulants.
Thrombus is inappropriate activation of haemostatic mechanisms.
Arterial –main component platelet, fibrin less (anti-platelets preferred)
Venous –main component fibrin, platelet less (anti-coagulants preferred)
Process of fibrin digestion by plasmin.
Plasminogen and plasmin have special kringles that bind exposed lysines or fibrin clot.
Inhibition of fibrinolysis
Endothelial cells synthesize and release plasminogen activator inhibitor (PA-1) which inhibits tissue plasminogen activator. Alpha 2 antiplasmin in blood binds to non-clot bound proteins, inactivating them.
Treatment of clotting abnormalities
- Drugs that interfere with clotting of blood
- Drugs that interfere with platelet aggregation
- If thrombosis, fibrinolytics
According to Use
Used In Vitro
2. Ca+2 complexing agents / Ca+2 chelators
a. Na+ / K citrate
b. Na+ / K+ oxalate
c. EDTA (ethylenediamine tetra-acetic acid)
Used In Vivo
According to route of administration
1. Indirect Thrombin inhibitors
1. Vitamin K antagonists
a. Coumarin derivatives
b. Indandione derivatives