Platelets

Question 1

What is the function of platelets?

Answer 1

Platelets trigger primary haemostasis (clotting) in response to injury.
Initiated when subendothelial collagen is exposed or in response to endothelial cell inflammatory protein release

Platelets are involved in
Continuous support of vascular integrity
Haemostatic plug formation
Fibrin clot formation

Question 2

What can dysfunctional platelets lead to?

Answer 2

Haemorrhage (excessive bleeding )
or
Thrombosis (excessive clotting)

Question 3

What is the structure of platelets?

Answer 3

~2/3 are in the circulation; ~1/3 sequestered in spleen
Disc shaped in blood
Surface charge: negative
Size: ~2.5 µm diameter/8-10fL
Anuclear, motile and complex

Question 4

What is the pathway from stem cell to platelets?

Answer 4

Stem cell > Common myeloid progenitor > Megakaryocyte-erythrocyte progenitor > megakaryoblast > megakaryocyte > platelets

Question 5

What are factors that affect thrombopoiesis

Answer 5

Thrombopoietin, IL-3, IL-6, and IL-11

Question 6

What are the four zones of platelets

Answer 6

Peripheral Zone
- communicates with the outside environment
- Contains small channels called the canicular system that connects the cell’s interior with the external environment

Structural Zone
- Helps the platelet change shape

Organelle Zone
Membrane System

Question 7

What causes clotting compounds to be released?

Answer 7

when stimulated to do so via ligand signals/interactions
○ Subendothelial collagen—exposed during injury

Cell inflammatory signals - released by endothelial cells

Question 8

What are the platelet alpha granules?

Answer 8

Proteins
- Fibrinogen – clotting factor
- Platelet factor 4 (PF4) – binds heparin (inhibits inhibition of clotting!)
- β-thromboglobulin – chemoattractant & stimulator of mitosis
- Plasminogen – role in fibrinolysis (breaks down clots when activated)
- Platelet derived growth factor (PDGF) – chemoattractant & mitogen

Question 9

What are the dense bodies in platelets?

Answer 9

Non-proteins
ADP, ATP, serotonin, calcium

Question 10

What are the lysosomes in platelets and what are they for?

Answer 10

Hydrolytic enzymes (catalase, acid phosphatase proteins)
Digest vessel wall matrix + debris

Question 11

What are prostaglandins?

Answer 11

• Small lipid compounds
• Thromboxane A2 (TxA2):
  ○ Produced by platelets
  ○ Prolongs constriction
  ○ Increase in TxA2 “switches on” platelets
• Prostacyclin (PGI2):
  ○ Decreases/inhibits platelet aggregation
  Prostaglandin produced by endothelial cell

Question 12

What are the receptors on platelets?

Answer 12

Protease-activated Receptor (PAR) - binds thrombin
Purine receptors (P2Y1 & P2Y12) - bind adenosine diphosphate (ADP)
α2- adrenergic receptor- binds adrenaline/epinephrine

Question 13

What are some STR G-protein couples receptors?

Answer 13

P2Y1
binds to Adenosine Diphosphate (ADP)
Induces platelet shape change
initiates primary wave of platelet aggregation (Ca+2)
P2Y12
major ADP receptor initiates full platelet aggregation

Question 14

What does glycoprotein Ib/IX/V do?

Answer 14

binds von Willebrand factor (vWf) on endothelial cells promoting adhesion & aggregation

Question 15

What does glycoprotein IIb-IIA do?

Answer 15

Binds fibrinogen, generates inter-platelet cohesion/aggregation

Question 16

What does Glycoprotein Ia/IIa, VI do>

Answer 16

Binds subendothelial collagen uncovered as a result of damage promoting tethering

Question 17

What is haemostasis?

Answer 17

“blood equilibrium”

Question 18

What is primary haemostasis?

Answer 18

Involves blood vessels and platelets in response to vascular injury

Question 19

What is secondary haemostasis?

Answer 19

Activation of circulating coagulation proteins in plasma resulting in the formation of a fibrin clot (multiple lectures later)

Question 20

What is the firs thing that happens during tissue damage induced clotting?

Answer 20

vWF exposed following endothelial damage is bound by platelet GPIb/IX/V complex

Question 21

What is the second step in tissue damage induced clotting?

Answer 21

Secretion: Platelets release granules (Thromboxane/ADP) that attract other platelets

Question 22

What is the third step of tissue-damage-induced clotting?

Answer 22

Tethering: GPVI binds to collagen followed by GPIa/IIb which also binds to collagen

Question 23

What is step four in tissue damage induced clotting?

Answer 23

Aggregation: GPIIb/IIIa-fibrinogen-GPIIb/IIIa bonds form aggregating platelets

Question 24

What is primary hemostasis activated by?

Answer 24

Injury to a blood vessel

Question 25

What is secondary haemostasis activated by?

Answer 25

Large injuries to blood vessels and surrounding tissues?

Question 26

What are platelet functions during clotting?

Answer 26

Adhesion, aggregation, and secretion

Question 27

What laboratory evaluation can be done for platelets?

Answer 27

Platelet count Blood film Bleeding time Platelet aggregation Platelet Function Analyser Flow cytometry

Question 28

What are the types of platelet function tests?

Answer 28

Optical aggregometry of platelet-rich plasma Platelet Function Assay (PFA 100)

Question 29

What are pre-analytical variables for platelet aggregometry?

Answer 29

Drugs, diet, lipaemia, platelet count, venepuncture, anticoagulant, transport conditions/time

Question 30

What is Platelet Function Assay (PFA)?

Answer 30

PFA replaces the bleeding time test Replicates conditions of flow to replicate shear forces on platelets