Haemostasis

Question 1

Describe the origin, size and contents of a platelet

Answer 1

Small cytoplasmic fragments of a megakaryocyte
2-5um diameter
Lysosomes, dense granules and alpha-granules

Question 2

What important chemicals do the granules contain?

Answer 2

Lysosomes - proteases
Dense granules - ADP, serotonin (5-HT), NA, Ca2+ and Histamine
Alpha granules - coagulation factors, adhesion molecules, immunologic molecules, chemokines and growth/angiogenic regulators

Question 3

Three basic events that occur with vascular injury

Answer 3

Formation of platelet plug and then fibrin filament assembly

Clot resolution and repair

Question 4

How does the platelet plug initially form?
[Clue]
1. agonist trigger
2. PGVI activates
3. VW factor - fibrinogen
4. PGIIb and IIIa bridge

Answer 4

Agonists trigger platelets to adhere to the damaged endothelial and subendothelial tissue
(Collagen, thromboxane A2, ADP, thrombin, NA)

Platelet glycoprotein VI binds to collage, causing integrin activation, Ca2+ mobilisation, aggregation and degranulation (leads to clotting cascade)

Platelet glycoprotein !b binds Von Willebrand factor, which activates the platelets to release fibrinogen and cross link with one another

Bridges stabilise aggregation, forming between platelet glycoproteins IIb and IIIa

Question 5

Complete clotting cascade diagram

Answer 5

Found in haemostasis note

Question 6

What is the outcome of the clotting cascade?

Answer 6

Fibrinogen is activated to fibrin, which is an insoluble protein that can aggregate to form fibrils and then fibres, which can be crosslinked (loose clot to tight clot)

This stabilises the platelet plug

Question 7

What role do serpins play in regulating clot formation?

Answer 7

Serpins are serine protease inhibitors

A lot of the clotting factors are serine proteases, and so serpins act to inhibit clot formation

Question 8

Give an example of an important serpin

Answer 8

Anti thrombin III

Question 9

Outline the process of fibrinolysis

Answer 9

Plasminogen circulating in blood cleaved and activated by plasminogen activators to plasmin

Plasmin is a serpin whose key substrate is fibrin

Therefore plasmin helps break down clots

Question 10

Key inhibitor of plasmin

Answer 10

a2-antiplasmin