Haemostasis Flashcards
What is haemostasis?
process whereby haemorrhage (bleeding) following vascular injury is arrested.
What does haemostasis depend on?
blood vessel wall,
circulating platelets
coagulation factors
How does an intact cell wall prevent haemostasis through endothelial cells?(4)
Prostacyclin: - this causes vasodilation and inhibits platelet aggregation
Antithrombin & Protein C activator: - both inhibit coagulation
Tissue plasminogen activator: activates fibrinolysis
Von Willebrand
factor (vWF), which can bind platelets
What are the membrane receptors found in the membrane of platelets?
GPIa/IIb complex & GPVI which are receptors for collagen
Glycoproteins (GPIb & IIb/IIIa allows attachment of platelets to vWF, then to endothelium.
What is vasoconstriction?
Immediate vasoconstriction of the injured vessel and reflex constriction of adjacent small arteries and arterioles - responsible for an initial slowing of blood flow to the area of injury
reduced blood flow allows contact activation of platelets and coagulation factors
Describe platelet plug formation
- subendothelial collagen is exposed.
- von Willebrand Factor (vWF) is released causing the platelets to change form and adhere to the subendothelial collagen via GPIa/IIb.
- which activates it.
- platelets change their shape from a disc to a more rounded form and they release the contents of their granules (platelet release reaction),
- the most important content of which is ADP. The platelets are also stimulated to produce the prostaglandin, thromboxane A 2 , from arachidonic acid derived from the cell membrane.
- The release of ADP and thromboxane A 2 causes an interaction of other platelets with the adherent platelets and with each other (secondary platelet aggregation), thus leading to the formation of a platelet plug
Describe the coagulation cascade(5)
Extrinsic pathway
- Coagulation begins when tissue factor activated on the surface of injured cells binds and activate factor VII
- Recruitment of other clotting factors and activation of platelets (amplification). Factor 7 activates Factor 10 which turns prothrombin to thrombin
- Huge burst of thrombin from activated platelets change fibrinogen into fibrin (propagation).
- Intrinsic pathway activated by tissue damage and extrinsic pathway activated by surface contact.
- Each reaction requires phospholipid and specific co-factors, and calcium to bind them.
How is coagulation regulated? (3)
Anti-thrombin - an important inhibitor of terminal proteins of cascade especially FXa and thrombin (Heparin potentiates its action markedly)
- Protein C and S.- Protein C is vit K-dependent and inactivates the cofactors of Va and VIIIa, and stimulates fibrinolysis. Protein S acts as cofactor for C.
- Tissue Factor pathway inhibitor (TFPI) - inactivates factor Xa and then the TFPI/FXa complex inhibits FVIIa
What is fibrinolysis?(3)
Fibrinolysis (like coagulation) is a normal haemostatic response to vascular injury.
is the enzymatic breakdown of fibrin in blood clots
fibrin is degraded by plasmin
Describe the steps of fibrinolysis
- Plasminogen (precursor) is activated by tissue plasminogen activator (t-PA).
- Produces plasmin, an enzyme which metabolises clots.
- Fibrin degradation products (FDP), such as D dimers from the degradation of cross-linked fibrin, are produced.
What is thrombosis?(3)
the pathological process whereby platelets and fibrin interact with the vessel wall to form a haemostatic plug to cause vascular obstruction
may be arterial, causing ischaemia
or venous, leading to stasis
What can thrombosis lead to?(4)
underlies ischaemic heart, cerebrovascular and peripheral vascular diseases, venous occlusion and pulmonary embolism.
How can defective haemostasis arise?(3)
A vascular disorder
Thrombocytopenia or a disorder of platelet function
Defective blood coagulation
Summarise the screening tests
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
Thrombin (clotting) time (TT)
What is Prothrombin Time (PT) ?(2)
measures factors VII, X, V, prothrombin (II) and fibrinogen
Tissue thromboplastin (a brain extract) or [synthetic] tissue factor with lipids and calcium is added to citrated plasma