## Introduction
Haemostasis is the process of forming clots in the wall of damaged vessels and preventing blood loss while maintaining blood in a fluid state within the vascular system.
## Site
Ruptured blood vessels
## Events
Whenever a vessel is severed or ruptured, haemostasis is achieved by the following mechanisms; Vasoconstriction Platelet aggregation & plug formation Coagulation (formation of blood clot) Clot retraction and repair Fibrinolysis
### Vasoconstriction
When the blood vessels are cut; The endothelium is damaged and the collagen is exposed The platelets adhere to this collagen and get activated The activated platelets secrete serotonin and other vasoconstrictor substances which cause constriction of the blood vessels
### Platelet plug formation (primary haemostasis)
The platelets get adhered to the collagen of ruptured blood vessel (and to a protein called *von willebrand factor*) and secrete ADP and thromboxane A2 These two substances attract more platelets and activates them All these platelets aggregate together and form a loose temporary platelet plug which closes the vessel and prevents further blood loss
### Coagulation (secondary haemostasis)
Involves;
* Formation of prothrombin activator
* Extrinsic pathway (abt 30 secs)
* Intrinsic pathway (4-6 mins)
* Conversion of prothrombin into thrombin
* Conversion of fibrinogen into fibrin
* Polymerization of fibrin monomers
* Polymerized fibrin strands form a meshwork on aggregated platelets and blood cells forming the blood clot sealing the damage in the vessel.
* Factor XIII tightens the clot
### Clot retraction and repair
Platelets contract causing the blood clot to retract expelling serum and pulling the edges of the broken blood vessels together enhancing repair of the damage Platelets also secrete Platelet Derived Growth Factor (PDGF) and Vascular Endothelial Growth Factors (VEGF) that enhance the healing process
### Fibrinolysis
Thrombomodulin-thrombin complex activates protein C
Activated protein C (APC) inactivates factor V & VIII in the presence of protein S APC also inactivates t-PA inhibitor Plasminogen is activated to plasmin by t-PA
Plasmin digests fibrin fibers causing lysis of unnecessary blood clot By this time, injured vessels have already healed
## Regulation
The following substances regulate haemostasis
* Serotonin
* ADP
* Thromboxane A2
* HMW Kinogen
* Kallikrien
* Platelet Factor-3 (PF-3)
* Calcium
* Thrombin
* Platelets
* Platelet Derived Growth Factor (PDGF)
* Vascular Endothelial Growth Factors (VEGF)
* Tissue Plasminogen Activator (t-PA)
* Urokinase plasminogen activator (u-PA)
## Prevention Of Blood Clotting
In a normal blood vessel, the following factors contribute to prevention of blood clot formation;
* Smoothness of the endothelial cell surface – prevents the activation of the intrinsic clotting system
* A layer of glycocalyx on the endothelium which repels clotting factors and platelets
* Nitric Oxide (NO) – inhibits platelet aggregation
* Prostacyclin (PGI2) – inhibits platelet aggregation
* Thrombomodulin (binds thrombin) – slowing the clothing process by removing thrombin.
Thrombomodulin-thrombin complex further activates protein C
Protein C – Inactivates Factors V & VIII
Anti-thrombin III – Inactivates Factors II, IX & V
Heparin – binds with anti-thrombin III, enhancing its effects. Inactivates Factors IX, X, XI & XII
## Regulation
The following substances regulate hemostasis:
* Serotonin
* ADP
* Thromboxane A2
* HMW Kinogen
* Kallikrein
* Platelet Factor-3 (PF-3)
* Calcium
* Thrombin
* Platelets
* Platelet Derived Growth Factor (PDGF)
* Vascular Endothelial Growth Factors (VEGF)
* Tissue Plasminogen Activator (t-PA)
* Urokinase plasminogen activator (u-PA)
## Prevention Of Blood Clotting
In a normal blood vessel, the following factors contribute to prevention of blood clot formation:
* Smoothness of the endothelial cell surface
* A layer of glycocalyx on the endothelium
* Nitric Oxide (NO)
* Prostacyclin (PGI2)
* Thrombomodulin
* Protein C
* Anti-thrombin III
* Heparin
## Clinical Correlates
The following conditions can disrupt the delicate balance of hemostasis and lead to clotting disorders:
* Vitamin K deficiency
* Haemophilia A (classic haemophilia)
* Haemophilia B (Christmas disease)
* Thrombophilia
* Thrombocytopaenia
* Von Willebrand disease
These disorders can lead to serious complications such as:
* Embolism
* Pulmonary embolism
* Ischemia
* Necrosis and infarction
* Myocardial infarction
* Stroke
