lecture 7 - coagulation Flashcards
What are the 3 pathways of the coagulation cascade?
Intrinsic, Extrinsic, Common
What activates the intrinsic pathway of the coagulation cascade?
Collagen exposure (contact activation)
What activates the extrinsic pathway of the coagulation cascade?
Tissue Factor (which binds to Factor VII)
Which factors are involved in the intrinsic pathway of the coagulation cascade?
Factors XII, XI, IX, VIII
Which factors are involved in the extrinsic pathway of the coagulation cascade?
Factor VII
Which factors are involved in the common pathway of the coagulation cascade?
Factors X, Xa, V, II (prothrombin), I (fibrinogen)
How do factors get activated in the coagulation cascade?
By cleavage (proteolytic reactions)
What are the steps in the extrinsic pathway of the coagulation cascade?
- Expression of tissue factor
- TF binds to FVII, which is coverted to FVIIa
- FVIIa activates FX to FXa
- Common pathway…..
What triggers the exposure of tissue factor?
Damage to blood vessel endothelium, resulting in exposure off underlying tissue factor lipoprotein
What are the steps in the intrinsic pathway of the coagulation cascade?
- Collagen fibres exposed
- FVII binds to collagen
- FVII activates FVI
- FVI activates FIX,
- FIX and FXIII activate FX
- common pathway…
How is the function of the extrinsic pathway measured in the laboratory?
Via Prothrombin Time or INR (international normalised ratio)
What are the steps in the common pathway of the coagulation cascade?
- FX activates to FXa with help of cofactor FV
- FXa activates prothrombin (FII) to convert it thrombin
- Thrombin activates fibrinogen to fibrin
- Fibrin forms the clot
Which pathway is factor VIII involved in in the coagulation cascade?
Intrinsic pathway
What are the 2 key cofactors in the coagulation cascade?
Factor V, Factor VIII
Where is FV involved in the coagulation cascade?
Common pathway - helps in conversion of prothrombin to thrombin
What assist in the coagulation cascade, besides cofactors?
Ca2+, phospholipid, Vitamin k
On what cells does the coagulation cascade often occur?
Platelets (on their phospholipid membranes)
How is the function of the intrinsic pathway of the coagulation cascade measured in the laboratory?
Activated partial thromboplastin time (APTT)
What is the function of FXIII in coagulation?
It crosslinks the fibrin to strengthen the clot
What is the process of dissolving a blood clot?
Fibrinolysis
What is the process of fibrinolysis?
Plasminogen in the clot is converted plasmin, which breaks down the fibrin and makes it soluble
What degradation product of fibrinolysis can be measured in the laboratory?
D-dimers
What are the 2 main sources of coagulation factors?
Liver (most factors), endothelium (von Wilebrand factor)
Which factors and proteins rely on Vitamin K for post-translational modifications, and therefore activation and function?
‘1972’ - X, IX, VII, II (prothrombin)
Proteins C & S
What is the most commonly used Vitamin K antagonist?
Warfarin
What factors in the coagulation cascade does warfarin inhibit the activation of?
X, IX, VII, II
What are the 3 main naturally and normally occurring inhibitors of blood coagulation?
Antithrombin, Protein C, Protein S
What activates plasminogen to plasmin?
tPA (tissue plasminogen activator)
