Haemostasis Flashcards
Primary Haemostasis Steps
Activation of platelets
Platelets bind to exposed collagen in sub endothelium of damaged vessels
Formation of platelet plug
Limits bleeding immediately
Secondary Haemostasis Steps
Enzymatic activation of coagulation factors to produce fibrin to stabilise plug
Gradually stable plug dissolved by fibrinolysis
2 Requirements for Haemostasis
Signal amplification
Feedback inhibition
Blood Clot Formation
Damaged blood vessel
Coagulation system activated
Vessel constricts
Activated platelets adhere to damaged blood vessel and each other to form platelet plug. RBCs trapped
Fibrin produced, binds to & stabilises plug
Factors in Intrinsic Coagulation Cascade
FXII
FXI
FIX
(FVIII)
Factors in Extrinsic Coagulation Cascade
FIII
FVII
Factors in Common Coagulation Cascade
FX
Prothrombin -> Thrombin
Fibrinogen -> Fibrin
Initiation Phase
Blood vessel injury exposes tissue fluid to blood
Tissue fluid binds FVIIa
TF/VIIa activates FIX & FX
Slow generation of thrombin
Amplification Phase
FIXa & FXa activate FVIII & FV on platelet surface
Amplifies thrombin generation
Thrombin converts fibrinogen -> fibrin
FXIIIa crosslinks fibrin fibres
Tissue Factor Pathway Inhibitor (TFPI)
FXa binds TFPI
FXa/TFPI binds TF/FVIIa
4º complex inhibits FXa & FVIIa activity
Initiation phase ends
Cascade Theory
predicts serious bleeding if early factors deficient but FXII deficiency = no bleeding and FXI deficiency = mild bleeding
Current Model
Activation exclusively through extrinsic pathway, triggered by tissue factor exposure to blood. Intrinsic pathway amplifies initial activation
Multiprotein complexes require:
Activated serine protease - FIXa or FXa
Cofactor - FVIIIa or FV
Ca2+ ions - released by platelets
-vely charged PL surface
Formation of complex increases activity of serine protease by ______
x50
Tenase Complex
FVIIIa binds to PL surface on platelets
FIXa binds to cofactor FVIIIa at platelet surface
Sustained FXa production
