Lecture 2.2 - HAEMOSTASIS

Question 1

Platelet activation

Answer 1

1.
Shape change from discoid to spiny

2.
Flip flop of membrane lipids resulting in a change of the external surface from neutral to charged

3.
Release of storage granules

4.
Conformational change of GPIIb/IIIa allowing for the binding of fibrinogen

Question 2

CONSEQUENCES of platelet activation

Answer 2

1.
Shape change leads to a huge increase in surface area

2.
Membrane flip flop exposes charged phospholipids to support coagulation

3.
Release of granule contents
-Increased concentration of certain clotting factors
-Further activation of other platelets–dense granule ADP release

There is a resultant cycle of aggregation leading to the formation of a large mass or plug of platelets over the layer of platelets covering the breach in the endothelium This plug is friable but supports the generation of a stronger fibrin clot

Question 3

Amplification:

Answer 3

the site of the reaction moves to the platelet and thrombin activates V, VIII and XI

Question 4

Propagation:

Answer 4

the formation of the bulk of the fibrin clot

Question 5

Antithrombin

Answer 5

• Acts against thrombin as well as activated
factors Xa , IXa and XIa .
• Binds irreversibly with the activated factors
• Requires heparin as a catalyst
• The heparin comes from the endothelium

Question 6

Fibrinolysis

Answer 6

•The specificity of action of this pathway is increased by binding of tPA and
plasminogen to fibrin as the clot is being formed

•Bound tPA is much more effective than unbound , thus preventing plasmin
being formed away from the clot

•The inhibitors of tPA and plasmin, PAI and alpha 2 antiplasmin, do not work as
well when their substrates are bound to fibrin

•Both tPA and PAI are synthesised in the endothelium

Question 7

Fibrinogen forms bridges between platelets using the GPIb receptor
TRUE/ FALSE

Answer 7

?

Question 8

Platelet α granules contain ADP and calcium

TRUE/ FALSE

Answer 8

?

Question 9

The platelet collagen receptor is a G protein coupled receptor
TRUE/ FALSE

Answer 9

?

Question 10

Thrombin is the most potent platelet agonist

TRUE/ FALSE

Answer 10

?

Question 11

During platelet activation, the membrane changes so that there is a negative charge on
the surface
TRUE/ FALSE

Answer 11

?

Question 12

Activation of the integrin, GPIIbIIIa results from signalling within the platelet
TRUE/ FALSE

Answer 12

?

Question 13

Platelet adhesion is dependent on von Willebrand factor in the plasma
TRUE/ FALSE

Answer 13

?

Question 14

Platelet activation leads to recruitment of additional platelets to the platelet plug
TRUE/ FALSE

Answer 14

?

Question 15

Initiation of the coagulation cascade occurs on the platelet surface
TRUE/ FALSE

Answer 15

?

Question 16

Fibrin fibres are stabilised by the action of Factor XIIIa

TRUE/ FALSE

Answer 16

?

Question 17

Factor VII activates Factor X and Factor XI

TRUE/ FALSE

Answer 17

?

Question 18

The propagation phase of the coagulation cascade depends on the continued activity of
Factor VII
TRUE/ FALSE

Answer 18

?

Question 19

Calcium is necessary for the attachment of factors to phospholipid
TRUE/ FALSE

Answer 19

?

Question 20

Explain why the activation of Factor X and the activation of thrombin are very similar
reactions.

Answer 20

?

Question 21

Is thrombin attached to the phospholipid surface

Answer 21

?

Question 22

Fibrinolysis

Answer 22

•The specificity of action of this pathway is increased by binding of tPA and
plasminogen to fibrin as the clot is being formed

•Bound tPA is much more effective than unbound , thus preventing plasmin
being formed away from the clot

•The inhibitors of tPA and plasmin, PAI and alpha 2 antiplasmin, do not work as
well when their substrates are bound to fibrin

•Both tPA and PAI are synthesised in the endothelium

Question 23

Nitric oxide activates platelets

TRUE/ FALSE

Answer 23

?

Question 24

D dimers can be produced in the absence of Factor XIIIa

TRUE/ FALSE

Answer 24

?

Question 25

Antithrombin is secreted by the endothelium

TRUE/ FALSE

Answer 25

?

Question 26

Thrombomodulin converts prothrombotic thrombin into a molecule with antithrombotic
effects
TRUE/ FALSE

Answer 26

?

Question 27

Plasminogen can be activated to plasmin by factors other than tPA
TRUE/ FALSE

Answer 27

?

Question 28

Low molecular weight heparin can catalyse the reaction between thrombin and antithrombin
TRUE/ FALSE

Answer 28

?

Question 29

What makes fibrinolysis more specific for the breakdown of fibrin than fibrinogen?

Answer 29

?

Question 30

What different aspects of coagulation and anticoagulation are enabled by thrombin

Answer 30

?

Question 31

Factor XII is activated by repeating surfaces

TRUE/ FALSE

Answer 31

?

Question 32

Factor XII is activated by high molecular weight kininogen

TRUE/ FALSE

Answer 32

?

Question 33

Factor XI can be carried by HMK

TRUE/ FALSE

Answer 33

?

Question 34

Why is the division of the coagulation pathways into intrinsic and extrinsic pathways
inappropriate for in vivo haemostasis?

Answer 34

?

Question 35

What is the evidence for the contact pathway’s involvement with the immune system?

Answer 35

?

Question 36

What positive feedback loops are there in the haemostatic pathways?

Answer 36

?