Coagulation Cascade Flashcards
Give some general characteristics of the coagulation cascade:
- what are the pathways?
- what are the enzyme factors involved?
- how do we activate enzymes?
- How does the cascade cause amplification?
2 pathways: Intrinsic + Extrinsic
6 enzyme factors XII, XI, X, IX, VII, II (thrombin)
- Serine proteases - chops up precursor + activates next molecule
Proteolytic cleavages, zymogens (inactive protease) converted to activated proteases
Amplification - chop up small bits of inactive factors to active factors which accumulate to large amounts
What are the events that occur when a blood vessel is damaged?
What triggers coagulation?
Tissue factor
Factor III
Discuss the intrinsic pathway
The intrinsic cascade is initiated when contact is made between blood and exposed negatively charged surfaces e.g when damaging blood vessel
Starts with factor XII (12)
Cell injury/vessel disruption exposes collagen which causes FXII to convert to FXIIa
This activates FXI which activates FIX
Discuss the extrinsic pathway
The extrinsic pathway is initiated upon vascular injury (damaged tissue) which leads to exposure of tissue factor, TF (also identified as factor III), a subendothelial cell-surface glycoprotein that binds phospholipid
Starts with tissue factor
Found in 3 different places
- Inside cells, on cell membranes, extracellular fluid inactive form
What is GLA domain?
Glutamate domain helps coagulation factor bind to phospholipid membranes
What type of protein is fibrinogen?
Fibrous
What inhibits the coagulation cascade pathways?
Anticoagulants
Discuss Haemophilia A?
What does it cause?
How is it managed?
Genetic - carried on X chromosome (males mostly affected)
Low/lack factor VIII (8) of the clotting cascade
Due to the absence/low factor 8, can cause prolonged bleeding + haemorrhage
Treat by injecting factor 8 or ADH (vasopressin) - this increases factor 8
Discuss Haemophilia B
Deficiency of Factor IX (9)
Treated w/ prophylactic factor 9
Lab test used in relation to coagulation are:
- bleeding time
- prothrombin time
- activated partial thromboplastin
What are the functions of these?
Prothrombin time (PT/ INR)
Measures the ability of the blood to coagulate (following addition to thromboplastin)
Examines extrinisc pathway + common pathway
Time is increased by abnormalities of factor VII, X, V, II,I, liver disease or warfarin
Bleeding time
Incision to forearm w/ venous cuff
Time how long blood takes to stop bleeding at injury
Bleeding time increases w/ platelet dysfunction (reduction of platelets)
Activated partial thromboplastin time (APTT)
Examines intrinsic pathway
Altered by changes in factors XII, XI, IX, VIII, X, V, II or I
Function of Vitamin K
What would if there is a lack of vitamin K?
What is warfarin?
Who uses warfarin?
Required for prothrombin synthesis, FIX, FVII, FX
It adds an extra carboxylate onto glutamate side chains
Lack of vitamin K causes loss of factor production + bleeding
People with AF (atrial fibrillation) artificial heart valves are treated with warfarin
Warfarin is a vitamin K antagonist (similar structure)
