haemostasis and thrombosis

Question 1

define haemostatic system

Answer 1

balance between clotting to stop bleeding to death, and not thrombosing to stop perfusion

Question 2

blood components involved in haemostasis

Answer 2

plasma, coagulation factos, regulatory proteins

Question 3

factors and cofactors involved in haemostasis

Answer 3

vWF, platelets, pro-coagulant proteins (e.g. VIIa)

Question 4

what triggers cogagulation from outside circulation

Answer 4

collagen, tissue factor

Question 5

what is von Willebrand Factor (vWF)

Answer 5

giant adhesive plasma proteins that have many binding sites for platelets, collagen and factor VIII

Question 6

structure of vWF

Answer 6

assembled to multimers and rolled up in blood to hide binding sites

Question 7

what happens to vWF upon collagen binding

Answer 7

shear stress of blood causes it to unravel and become long and thin, exposing binding sites

Question 8

what are platelets

Answer 8

enucleated fragments of megakaryocyte containing granules of vWF, fibrinogen and ADP

Question 9

structure of platelets

Answer 9

possess adhesive surface receptors that can bind to vWF and collagen; stimulatory receptors can be activated by ADP (purine receptors), thromboxane and PGI2

Question 10

platelets upon activation

Answer 10

changes shape to expose phospholipids, present proteins and release granules

Question 11

how do platelets bind to vWF and why

Answer 11

via GP1b to slowdown and allow secondary collagen binding for activation

Question 12

how can platelets bind to other platelets and what is the outcome

Answer 12

by fibrinogen, causing Ca2+ influx and degranulation

Question 13

what is produced in platetets using phospholipids from the surface

Answer 13

thromboxane A2

Question 14

where are clotting factors mostly synthesised

Answer 14

liver

Question 15

where is vWF and clotting factor VIII synthesised

Answer 15

endothelium

Question 16

3 stages of haemostasis

Answer 16

vasoconstriction (due to endothelin and neural activity), primary (platelet plug formation), secondary (fibrin mesh stabilises platelet plug)

Question 17

what is primary haemostasis sufficient for

Answer 17

small vessels

Question 18

formation of platelet plug

Answer 18

endothelium damaged, causing blood to meet collagen/tissue factors → rolled up vWF binds to exposed collagen → stretches and exposes platelet binding sites → vWF binds to GP1b receptors on platelets → platelets change shape and release alpha granules (fibrinogen and vWF), dense granules (serotonin, ADP and Ca2+) → platelets present activated GPIIb/IIIa receptors → vWF released enables more platelets to be captured, while fibrinogen allows platelets to stick together using GPIIb/IIIa

Question 19

what is a fibrin mesh required for

Answer 19

larger vessels, stabilise platelet plugs

Question 20

formation of fibrin mesh

Answer 20

endothelium damaged, causing blood to meet collagen/tissue factors → circulating FVIIa binds to newly exposed tissue factors → complex forms that converts FIX to FIXa and FX to FXa → TFPI binds to FVIIa, FIXa and FXa to stop, but if stimulus large enough FXa converts FII to thrombin → thrombin activates FVIII and FV → make complexes with Ca2+, phospholipids, FIXa and FXa → FIXa converts FX to FXa → FXa converts FII to thrombin → levels of thrombin increase rapidly in thrombin burst, cleaving fibrinogen to insoluble fibrin that forms a mesh

Question 21

why is a fibrin mesh stronger

Answer 21

FXIII activated by thrombin forms fibrin cross links that are more resistant to fibrinolysis