Haemostasis
Definition
Physiological response to cessation of
bleeding and maintenance of vascular integrity
by formation of thrombus (platelets plus +fibrin clot)
Components
Phases
Coagulation cascade
Anticoagulant system
Assessment
Platelets
von Willebrands Factor (vWF)
Vascular endothelium
Soluble plasma proteins
Primary - platelet plug
Vascular injury exposes subendothelial factors (TF, collagen, fibronectin, vWF)
Platelets adhere and are activated
Platelets express surface proteins (e.g. GP IIb-IIIa)
Platelets release granules containing pro-coag factors
Fibrinogen binds to GP IIb-IIIa on platelet surface causing platelet aggregation
Secondary - fibrin clot
Coagulation cascade activated, thrombin generated
Thrombin cleaves fibrinogen to insoluble fibrin
Platelets and fibrin crosslinked by FXIII for stable thrombus
RBCs also become enmeshed in clot
Intrinsic pathway (platelet activation - 12, 11, 9, 10)
FXII - FXIIa
FXIIa activates FXI - FXIa
FXIa activates FIX - FIXa
FIX activates FX - FXa, forms prothrombinase complex
Common pathway (FXa onward - 5, 10, 2, 1, 8)
Prothrombinase cleaves prothrombin to thrombin (FIIa)
Thrombin cleaves fibrinogen to insoluble fibrin to form stable clot
Extrinsic pathway (tissue damage - TF, 7, 10)
Vessel wall damage esposes TF in vessel walls and endothelium
TF activates FVII (FVIIa)
FVIIa activates FX (FXa), forms prothrombinase complex (FXa-FVa)
Protein C
Vitamin K-dependent protein
Activated by thrombin activating thrombomodulin
Inactivates FVa and FVIIa (extrinsic pathway)
Protein S
Cofactor for thrombmodulin in protein C activation
Antithrombin (AT)
Inhibits all activated coag enzymes
Particularly FIIa and FXa (common pathway)
Tissue factor pathway inhibitor
Forms complex with TF, FVIIa and FXa (extrinsic pathway)
Extrinsic pathway
Activity measured by prothrombin time (PT)
Intrinsic pathway
Activity measured by activated partial thromboplastin time (aPTT)
Intrinsic pathway
(platelet contact with damaged endothelium)
Extrinsic pathway
(trauma releases tissue factors)
Damaged endothelium
Trauma (TF)
XII
XIIa
XI
XIa
IX
IXa
VII
VIIa
XII
XIIa
XII
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II (prothrombin)
IIa (thrombin)
I (fibrinogen)
Ia (fibrin)
V
Va
XIII
XIIIa
Crosslinked fibrin clot