Platelet biochemistry

Question 1

Platelets in disease

Answer 1

Thrombosis - formation of a clot inside a blood vessel.
Platelets have a central role in arterial thrombosis.

Question 2

Activation

Answer 2

This causes platelet shape change.
Smooth discoid - spiculated and pseudopodia.
Increases SA.
Increases possibility of cell-cell interactions.

Question 3

Glycoprotein IIb/IIIa (GP IIb/IIIa) receptor

Answer 3

On the surface of platelets - 50,000 to 100,000 copies on resting membrane.
Platelet activation - increases number of receptors, increases affinity of receptor for fibrinogen which links receptors binding the platelets together.
Also known as integrin aIIbB3.

Question 4

Platelet receptors

Answer 4

After atherosclerotic plaque rupture:
- platelets adhere to damaged vessel wall - collagen receptors bind to subendothelial collagen - exposed by endothelial damage - GPIIb/IIIa also binds to von Willebrand factor (VWF) which is attached to collagen.
Soluble agonists are also released and activate platelets.

Question 5

Cyclooxygenase 1 and 2

Answer 5

In platelets - COX-1 converts Arachidonic acid to Prostaglandin H2.
In endothelial cells - COX-1 and 2 converts Arachidonic acid to Prostaglandin H2.
COX-1 - mediates GI mucosal integrity Thromboxane A2-mediated platelet aggregation.
COX-2 - mediated inflammation. Involved in prostacyclin production which inhibits platelet aggregation and affects renal function.
Aspirin - low dose inhibits COX-1, high dose inhibits both.

Question 6

Agonists

Answer 6

Cause platelet activation.
- Collagen.
- Thrombin.
- ADP.
- Thromboxane A2.
Aspirin inhibits an amplification pathway.

Question 7

G proteins

Answer 7

Different G proteins link to different signalling pathways - by ADP.

Question 8

ADP-induced platelets aggregation

Answer 8

Can activate P2Y1
- causes platelet activation.
- results in GPIIb/IIIa fibrinogen cross-linking and aggregation.
Can activate P2Y12
- sustains platelet activation and aggregation.
Released by dense granules.

Question 9

Thrombin

Answer 9

Activates protease-activated receptors on platelets.
This leads to platelet activation and release of ADP which amplifies this activation.

Question 10

Procoagulant activity - lipid bilayer

Answer 10

Platelet activation - Ca2+ release from intracellular stores - inhibits translocase and activates scramblase leads to expression of aminophospholipids on the outer platelet membrane - assembles prothrombinase complex and generates thrombin.

Question 11

Platelet-fibrin clot

Answer 11

Fibrin strands.
Platelets.
Trapped RBCs.

Question 12

Fibrinolytic system

Answer 12

Healthy endothelium release tPA - cleaves plasminogen into plasmin.
This breaks down fibrin into fibrin degradation products.
PAI-1 and antiplasmin - inhibitors.

Question 13

Platelet alpha granules

Answer 13

Mediate expression of surface P-selectin and release of inflammatory mediators, adhesion molecules and coagulation factors.

Question 14

Inflammation

Answer 14

Platelets have pro-inflammatory and prothrombotic interactions with leukocytes and release inflammatory mediators from alpha granules.