Blood Coagulation Flashcards
Blood coagulation define :
Process by which blood changes from a liquid to a gel, forming a blood clot
Heamostasis define
Process enables the cessation of bleeding in response to vascular injury
Prevents blood loss + enables tissue repair
Thrombosis define:
Blood clots are formed when they are not needed; limit/ block blood flow (normally in vein)
Blood clot=thrombus
Embolism define:
When a thrombus breaks loose and travels from one location in the body to another: blood clot=embolism
Haemostasis steps
Blood vessel injury
Primary haemostasis =vasoconstriction + platelet plug formation
Secondary haemostasis = stable clot formation : coagulation cascade activation
Fibrinolysis/tertiary haemostasis = vessel repair and dissolution of clot
Primary haemostasis what happens simplified:
Vasoconstriction- reduces blood flow therefore reduces blood loss
Platelet plug formation- involving platelet adhesion, activation, aggregation
Steps in platelet plug formation:
Platelet adhesion
Platelet activation
Platelet aggregation
Platelet life span:
7-10 days
150,000-400,000 platelets per micro litre of blood
Platelet plug formation: adhesion explain
Breach of endothelial cells = exposure of collagen
vWF (von Willebrand factor) binds to collagen
GPIb-V-IX binds to vWF immobilised on collagen
GPVI and GPIa/IIa (a2B1) binds to exposed collagen
Platelet plug formation: Activation
Platelets change shape
Release vWF,fibrinogen,ADP, TXA2
ADP( binds to P2Y12 receptors on platelets) and TXA2 bind to TXA2 receptors on platelets ; both activating GPIIb/IIIa
Platelet plug formation: aggregation
Activation of GPIIb/IIIa receptor
GPIIb/IIIa binds to fibrinogen
GPIIb/IIIa vWF
=Bridges between platelets / aggregation
Coagulation factors : what does a mean? X to Xa
X= inactive precursor
Xa= active
Secondary haemostasis simplified
Stable clot formation; coagulation cascade activation- end result is the activation of thrombin which :
- converts fibrinogen to fibrin
- induces more platelet recruitment and activation
Pathways in coagulation cascade
Extrinsic / Tissue factor pathway
Intrinsic / Contact pathway
Common pathway
coagulation cascade: Extrinsic / Tissue factor pathway what happens?
Activated by ‘extrinsic’ factors- exposure of endothelial TF following injury
III (Tissue factor) interacts with factor VII to activate= VIIIa to activate factor X to Xa = extrinsic tenase complex
factor VII to activate= VIIIa needs?
Vitamin K
And tissue factor (III) -when in blood
coagulation cascade:Intrinsic/ Contact pathway what happens?
Activated by ‘intrinsic’ factors present in blood
Factor XII —> XIIa which activates factor XI to XIa which activates IX to IXa
Then intrinsic tenase complex
Intrinsic tenase complex
Factor XIa activates IX (to IXa) which combines with VIIa to activate Factor X —> Xa
Extrinsic tease complex
III (Tissue factor) interacts with factor VII to activate= VIIIa to activate factor X to Xa
Prothrombinase complex
Factor Xa , Va and Calcium bind together
Prothrombinase complex activates?
Prothrombin (factor II ) into thrombin (factor IIa)
coagulation cascade:Common pathway what happens?
May result after the activation of factor X at the end of either pathway.
Prothrombinase complex formed = activates prothrombin (factor II) into thrombin (factor IIa).
Thrombin (IIa) activates factor I (fibrinogen) to Ia (fibrin). Which binds to XIIIa to form cross-linked fibres
Factor IIa (thrombin) can also bind to? (Despite factor I)
PPAR receptor on platelets —> platelet activation/aggregation
Important brakes on the coagulation cascade
Look notes
Fibrinolysis
To break down fibrin
Tertiary haemostasis
Fibrinolysis
Thrombolysis
Tissue plasminogen Activator factor (t-PA) -PRODUCED BY ENDOTHELIAL CELLS
Convert plasminogen to plasmin
Factor Ia(fibrin) converted to fibrin degradation products
Haemostatic balance
Equilibrium between pro-coagulant/pro-thrombothic and anticoagulant /anti- thrombothic factors
Pro-thrombin factors and anti-thrombotic factors
Pro-thrombin factors: increase in coagulation, platelets or decrease in Fibrinolysis
anti-thrombotic factors: decrease in coagulation, platelets or increase in Fibrinolysis
Haemostasis disbalance when there is more anti-thrombotic factors leads to?
Bleeding
Haemostasis disbalance when there is more pro-thrombotic factors leads to?
Thrombosis
Arterial thrombus vs venous thrombus
Arterial thrombus- white; large platelet component
Venous thrombus- red; large fibrin component and rbcS
Factors contributing to thrombosis
Described in Virchow’s triad
Hypercoagulability + vascular damage + circulatory stasis
If you have all 3= high risk at developing a thrombus
What serious medical problems caused by clots?
Venous thromboembolism (VTE)
-deep vein thrombosis
-pulmonary embolism
Heart attack from atherosclerosis
Stroke from atrial fibrillation
