Primary Haemostasis

Question 1

What is coagulation?

Answer 1

The process of of blood changing from its liquid state into a stable fibrin clot.

Question 2

What is thrombosis?

Answer 2

Local coagulation or clotting of the blood in part of the circulatory system.

Question 3

What is fibrinolysis?

Answer 3

The breakdown of a clot.

Question 4

What is haemostasis and how is it achieved (3)?

Answer 4

Haemostasis is the halting of blood following trauma to blood vessels.

It is achieved by:
Vasoconstriction
Formation of an unstable platelet plug at the site of the vessel wall damage
Formation of a stable fibrin clot.

Question 5

What is primary haemostasis?

Answer 5

Formation of an unstable platelet plug.

Question 6

What are platelets (describe structure)?

Answer 6

Discoid, non-nucleated, granule-containing cells that are derived from myeloid stem cells. They have glycoproteins in their membranes important for the platelet’s interactions.

Question 7

How are platelets formed?

Answer 7

They are formed in the bone marrow by the fragmentation of megakaryocyte cytoplasm.

Question 8

What is the circulating lifespan of platelets?

Answer 8

Around 10 days

Question 9

What do platelets do when exposed to a damages vessel?

Answer 9

They bind to the exposed collagen in the endothelium, either directly via the platelet GPIa receptor or indirectly via the Von Willebrand Factor (VWF), which binds to the platelet’s GPIb receptor.

Question 10

What receptor is used for the directly binding of a platelet to exposed collagen in the endothelium?

Answer 10

GPIa

Question 11

How do platelets indirectly bind to exposed collagen in the endothelium?

Answer 11

VWF binds to the GPIb receptor.

Question 12

What happens once platelets bind to collagen (3).

Hint: Shape, membrane, contents

Answer 12

They change shape from a disc to a more rounded form with spicules to encourage platelet-platelet interaction.

The platelet membrane is invaginate to form a surface-connected cannalicular system in which the contents of platelet granules are released, such as ADP, fibrinogen and VMF.

They also release their storage granules, alpha granules and dense granules.

Question 13

Platelets are also stimulates to form the prostaglandin Thromboxane A2. Where does it come from and what does it do?

Answer 13

Thromboxane A2 is formed from arachidonic acid derived from the cell membrane. As well as playing a role in platelet aggregation, it is also a known vasoconstrictor and is especially important during tissue injury and inflammation.

Question 14

The granular release of ADP and generation Thromboxane A2 create a positive feedback loop resulting in further platelet recruitment activation and aggregation. How do they do this?

Answer 14

ADP binds to P2Y12 receptor and Thromboxane A12 binds to the Thromboxane A2 receptor. This stimulates the activation of platelets, causing a conformational change in the GPIIb/IIIa receptor (known as inside out or flip-flopping).

Question 15

What do changes in the GPIIb/IIIa receptor shape allow?

Answer 15

This allows the binding of fibrinogen, causing outside-in signalling which further activates the platelets.

Question 16

What does fibrinogen do?

Answer 16

It links platelets together to form a platelet plug.

Question 17

How are the effects of fibrinogen counterbalanced to maintain haemostasis.

Answer 17

Endothelial cells release prostacyclin (PGI2), which vasodilates and suppresses platelet activation, preventing inappropriate platelet aggregation.

Question 18

What are two types of antiplatelet drugs?

Answer 18

Aspirin and Clopidogrel.

Question 19

How does aspirin work?

Answer 19

Inhibits the production of Thromboxane A2 by irreversibly blocking the action of cyclo-oxygenate (COX), resulting in a reduction of platelet aggregation. Although this would also inhibit prostacyclin too (something that stops clots from forming), endothelial cells are nucleated and can synthesise more COX whereas non nucleated platelets cannot.

The effects lasts for about 7 days until more platelets have been produced.

Question 20

How does Clopidogrel work?

Answer 20

It irreversibly blocks the ADP receptor P2Y12 on the platelet cell membrane. The effects of Clopidogrel last for 7 days until new platelets have been produced.

Question 21

What is VMF and where is it synthesised?

Answer 21

Von Willebrand Factor is a glycoprotein that is synthesised by endothelial cells and megakaryocytes and circulates in plasma as multimers of different sizes.

Question 22

What does VWF do?

Answer 22

It mediates the adhesion of platelets to sites of injury and promotes platelet-platelet adhesion. It is also a specific carrier for Factor VIII