Haemostasis Flashcards
What is haemostasis and what interactions are involved?
Haemostasis is a process whereby haemorrhage following vascular injury is arrested
This depends on closely linked interaction between:
Blood vessel wall
Circulating platelets
Coagulation factors
Response needs to be tightly controlled to prevent extensive clots developing and to be able to break down such clots once damage is repaired
How do vessel walls prevent haemostasis?
The intact vessel wall prevents haemostasis
Endothelial cells produce:
Prostacyclin- this causes vasodilation and inhibits platelet aggregation
Antithrombin & Protein C activator- both inhibit coagulation
Tissue plasminogen activator- activates fibrinolysis
What are platelets?
They are large disc-shaped with large surface area top absorb coagulation factors
Have membrane receptor agonists such as:
GPIa/llb complex & GPVI which are receptors for collagen
Glycoproteins (GPlb &llb/lla allows attachment of platelets to vWF which in turn is attached to the endothelium
How does vasoconstriction happen?
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 are of injury
Reduced blood flow allows contact activation of platelets and coagulation factors
How does the haemostatic pug form?
Following an injury, subendothelial collagen is exposed
von Willebrand Factor (vWF) is released causing the platelets to change form and adhere to the subendothelial collagen
After platelet adhesion, the subendothelial collagen binds to the receptors on the platelet which activates it
Activated platelet releases a number of important cytokines and chemical mediators from its granules
These include ADP, vWF, thromboxane A2, serotonin and coagulation factors
ADP promotes platelet aggregation to form primary haemostatic plug
Thromboxane A2 is also produced to potentiate aggregation
How does coagulation happen?
Thromboxane A2 also performs vasoconstrictor activities
Activated platelets accelerates coagulation process by providing membrane phospholipid
Proteins for coagulation cascade for proenzymes (serine proteases) and pro-factors
The cascade is divided on the basis of lab test into intrinsic, extrinsic and common pathways
Coagulation begins when tissue factor activated on the surface of injured cells binds and activate factor VII
What is the platelet reaction and the primary haemostatic plug formation?
Additional platelets from the circulating blood are drawn to the area of injury
Continuing platelet aggregation promotes the growth of the haemostatic plug which soon covers the exposed connective tissue
Unstable primary haemostatic plug produced by these platelet reactions in the 1st minute or so following injury- usually sufficient to provide temporary control of bleeding
What is the coagulation cascade?
Biochemical reactions of coagulation
Convert soluble fibrinogen into a meshwork of insoluble fibrin
Tightly regulated orchestration of coagulation factors, cofactors and inhibitors which result in the controlled formation of the pivotal enzyme thrombin which initiates fibrin formation
How is coagulation regulated?
Unchecked, blood coagulation would lead to dangerous occlusion of blood vessels (thrombosis)
Coagulation is modulated by 3 major inhibitory systems of inactivation of thrombin and other facotrs by other circulation inhibitors:
Anti-thrombin- an important inhibitor of terminal proteins of cascade especially Fxa and thrombin (Heparin potentiates its action markedly)
Proteins C and S- proteins C is vitamin K-dependent and inactivates the cofactors of Va and VIIIa and stimulates fibrinolysis.
Protein S acts as a cofactor for C
Tissue factor pathway inhibitor (TFPI)- inactivates factor Xa and then the TFPI/Fxa complex inhibits FVIIa
What is fibrinolysis?
Fibrinolysis, like coagulation, is a normal haemostatic response to vascular injury
It is the enzymatic breakdown of fibrin in blood clots
Fibrin is degraded by plasmin
Main functions are:
Clot limiting mechanism
Repair and healing mechanism
What is thrombosis?
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
How and why do we test for haemostatic function?
Defective haemostasis with abnormal bleeding may result from:
A vascular disorder
Thrombocytopenia or a disorder of platelet function
Defective blood coagulation
Simple tests are employed to assess the platelet, vessel wall and coagulation component of haemostasis
E.g. blood count and blood film examination, screening tests of blood coagulation, individual coagulation factor assays, assay of von Willebrand factor
Name some screening tests used to diagnose coagulation disorders?
Prothrombin Time (PT):
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
Activated Partial Thromboplastin Time (APTT)
Measures factors VII, IX, XI and XII in addition to factors X, V, prothrombin (II) and fibrinogen
Three substances- phospholipid, a surface activator (e.g. kaolin) and calcium are added to citrated plasma
Thrombin (clotting) time (TT):
Sensitive to a deficiency of fibrinogen or inhibition of thrombin
Diluted bovine thrombin is added to citrated plasma
What are the principles of clotting tests?
Incubate plasma with reagents necessary for coagulation Phospholipid, cofactors Trigger or activator Calcium Measure time taken to form fibrin clot
