Intact endothelium prevents clotting. How?
Healthy endothelium releases
Nitric oxide
Prostacyclin
Tissue plasminogen activator
What does nitric oxide do?
Inhibits platelet activation
What does prostacyclin do?
Vasodilation
What does tissue plasminogen activator do?
Promotes fibrinolysis
Vessel damage - beginning of blood clotting
Damage exposes subendothelial collagen.
Allows von willebrand factor - binds and recruit platelets
Tissue factor is also released
2nd step - extrinsic pathway activation
Tissue factor binds factor VIIa
This complex activates factor X which changes to Xa
3rd step - platelet activation triggers intrinsic pathway
Activated platelets
Release polyphosphate
Expose negatively charged phospholipids
These support activation of intrinsic pathway factors
4th step - common pathway
Both pathways (intrinsic and common) generate factor Xa
Converts prothrombin to thrombin
Thrombin converts fibrinogen to fibrin
Fibrinogen stabilises platelet plug to create fibrin clot
What is extrinsic pathway triggered by?
Tissue factor
What is extrinsic pathway measured by?
Prothrombin time
Intrinsic pathway is triggered by?
Activated platelets
What is intrinsic pathway measured by?
Activated partial thromboplastin time
What does the common pathway start at?
Factor Xa
Where classic and alternative pathway converge
What test is used to measure conversion of fibrinogen to fibrin
Thrombin time
What does prolonged Thrombin time indicate?
Low fibrinogen or abnormal fibrinogen
how is thrombin time measured?
Thrombin is added directly to plasma
How is fibrinogen activity measured?
Fibrinogen assay
How is extrinsic pathway measured?
Prothrombin time
What does prolonged prothrombin time indicate?
Deficiency in extrinsic factors (VII)
Or Common pathway
How is prothrombin time measured?
Thromboplastin used. - contains tissue factor
What is used for monitoring warfarin (vitamin K antagonist)?
International normalised ratio
How is the intrinsic pathway measured?
Activated partial partial thromboplastin time
What does activated partial thromboplastin time activate?
Factor XII
What does prolonged Activated partial thromboplastin time indicate?
Deficiency in intrinsic factors