Blood 5: Haemostasis Flashcards
Haemostasis is comprised of 2 phases…
Haemostatic response - slowing of flow and aggregation of platelets
Secondary phase - activation of clotting cascade with fibrin formation and haemostatic plug
How does vasoconstriction occur after vessel injury?
Smooth muscles cells are depolarised by injury and contract, platelets adhere and release thromboxane and serotonin which contribute to vasoconstriction
How does vessel wall injury contribute to haemostasis?
Loss of endothelium -> exposed collagen -> platelet adhesion -> activation of intrinsic pathway
Tissue factor is released by damaged cells activating extrinsic pathway
vWF is also released promoting platelet aggregation
How does normal endothelium prevent clotting?
Endothelium is coated with glycosaminoglycans which repel platelet aggregation. Heparen sulphate accelerates inactivation of clotting factors.
Protein C activated by endothelium
Describe platelets
Cytoplasmic fragments without nucleus, survive 8-10 days.
Have a dense tubular system stores Ca2+
Cytoplasm contains actin and myosin -> allows shape change
Describe the platelet reaction with damaged endothelium to cause release reaction
Adhesion to subendothelial collagen, depends on vWF.
Adherent platelets change from discs to spiny spheres. Release reaction occurs in which platelet granules are secreted - this is Ca2+ dependent.
Describe the platelets release reactions importance in activating clotting cascade
Granules release:
- serotonin which causes vasocontriction’
- ADP + thromboxane A2 cause further platelet aggregation
- Fibrinogen helps platelets bind to each other
- Coagulation factors are activated
- Thrombin causes further aggregation
- Fibrin forms and clot is irreversible plug
What is thromboxane A2?
Prostaglandin formed from arachidonic acid via COX in platelets.
Very powerful vasoconstrictor and platelet aggregator
What is Prostacyclin?
Is a prostaglandin form from arachidonic acid via COX in endothelium.
Powerful vasodilator and platelet inhibitor
What is the difference between intrinsic and extrinsic coagulation pathways?
Intrinsic - components are all in circulating blood
Extrinsic - requires tissue factor (release from damaged endothelium) to begin clotting
What are the Vitamin K dependent clotting factors?
II, VII, IX,X
What are the fibrinogen group factors?
Fibrinogen, V, VIII, XIII
All react with thrombin and are consumed or inactivated during coagulation
What anticoagulation factors exist?
Antithrombin III - inactivates thrombin by binding to in mole:mole to form insoluble product. Also inactivates F X
Protein C and Protein S inactivate V + VII
How does fibrinolysis occur?
Fibrin is broken down by plasmin.
Plasmin is formed from plasminogen - due largely to release of tissue plasminogen activator from endothelial cells
