Haemostasis, thrombosis and associated therapies

Arrest of blood loss from damaged vessels

Platelets are non adhesive and circulate singly. During vessel wall injury platelets aggregate. become stabilised by fibrin and arrest bleeding from several vessels.

Nitric oxide It causes vasodilation on blood capillaries

• Damage to blood vessel • Exposure of platelets to collagen and vWF in the extracellular matrix and later exposure to thrombin • Platelets activate and adhere • Release of mediators • Vasoconstriction + aggregation of platelets • Formation of a soft platelet plug

PH = the cellular phase of haemostasis. Platelets move towards the matrix. This then sticks and is activated by binding to either collagen or vWF. This activated the platelets which then activate fibrinogen (they connect to platelets via fibrinogen attachments). Clotting pathway Initiation - activated by Tissue Factor (made when the endothelium is damaged). This takes place on TF expressing cells in tissues after blood, with its clotting factors, leaks out the blood vessel. Amplification = initiated by thrombin. and involves activation of many factors including FV, FVII, FX. It takes place on activated platelets.

Fibrin and platelets

• usually associated with artherosclerosis (plaque building up around the arteries) • form at site of vascular injury • large platelet formation

• associated with turbulent flow of blood or vascular injury following surgery/trauma • platelet component, large fibrin component • red blood cell component

The treatment is a balancing act. This is between clot formation and the risk of haemorrhage.

It is a platelet agonist, vasoconstrictor. Major component of platelet COX-1 Low dose of aspirin - irreversible inhibition of cox-1

ADP stimulation of cells This causes irreversible clot formation.