Week 3 Flashcards
(29 cards)
Define coagulation
The conversion of liquid blood to a gel like solid.
Define haemostasis
The stopping of bleeding (not just clotting)
Define protease.
An enzyme which cleaves peptide bonds in their substrates.
Define proteolysis.
Cleavage of peptide bonds in proteins.
What are the three phases of haemostasis?
1 - vasoconstriction
2 - formation of platelet plug
3 - coagulation
Describe the normal plasma used in the clotting lab.
Citrated plasma (i.e. sodium citrate added to prevent coagulation in storage) from a bulk sample of plasmas obtained from at least 100 donors.
Why is a phospholipid/kaolin used in the clotting lab?
The reactions of the clotting cascade all take place on negatively charged phospholipid surfaces so kaolin is required for this experiment. Kaolin is an aluminium silicate clay on which a suspension of negatively charged phospholipids are adsorbed in order to initiate the cascade.
What reagents are used in the clotting lab?
- normal plasma (with sodium citrate)
- kaolin with adsorbed phospholipids
- calcium chloride solution
- chelated calcium chloride solution
- heparin solution
- thrombin
- benzamidine
What is Benzamidine?
A protease inhibitor.
What is heparin?
A naturally occurring glycosaminoglycan of varying chain lengths which is released from mast cells. It is an anticoagulant.
What is the APTT and what does it evaluate?
Activated Partial Thromboplastin Time - evaluates the intrinsic and common pathways of the clotting cascade.
What are the stages of an APTT?
- Plasma incubated with phospholipid and kaolin at 37C
- Calcium chloride added and incubation continues
- Time to clot formation measured
In an APTT, what surface does the phospholipid/kaolin mimic?
An activated platelet.
In the APTT, why is sodium citrate added to the plasma?
To prevent coagulation in storage.
What is the difference between blood serum and blood plasma?
Serum is plasma with fibrinogen removed aka the portion of plasma remaining after coagulation of blood.
When blood clots form naturally they are red. Why is this?
RBCs are trapped in the clot. (Plasma is used in the lab so no RBCs get trapped)
Why does benzamidine slow the time for plasma to clot?
It is a competitive protease inhibitor. As most of the coagulation factors are serine proteases, the benzamidine will compete for the active site of the enzymes. Binding to the active site is reversible so benzamidine will slow the process but not stop it completely.
Is calcium needed for thrombin action?
No. A clot will form without calcium. Calcium is needed to form thrombin but is not needed to convert fibrinogen to fibrin by thrombin.
Which pathway is the target for heparin action?
The final common pathway because it inhibits the action of thrombin so with thrombin inhibited the final common pathway will not occur.
What are the key stages of fibrinolysis?
- plasminogen becomes trapped in clot
- plasminogen is activated by serine protease tPA (tissue plasminogen activator)
- tPA converts plasminogen to plasmin
- plasmin breaks down fibrin mesh
After treatment with heparin has been started, why is it important to check the APTT?
- individual variation in coagulation means that effects of heparin are not predictable
- effects on the APTT predict the therapeutic effects well
- so checking the APTT ensures the dosage is appropriate
- too much heparin would increase the risk of bleeding/haemorrhage and too little would be ineffective
Why might streptokinase be an advantage to bacteria?
It acts in a similar way to tPA so can digest fibrin strands and break down a clot thus allowing the bacteria to gain access to tissues and bloodstream.
Will a patient with a deficiency of factor VII have a prolonged APTT?
No - factor VII is part of the extrinsic pathway so will not affect APTT.
Will a patient with a deficiency in factor VIII have a prolonged APTT?
Yes - factor VIII is part of the intrinsic pathway so a deficiency in this will lead to an increased APTT. (Haemophilia A)
