Platelet BioChemistry

Question 1

What is Thrombosis?

Answer 1

• Formation of clot (thrombus) inside blood vessel
• Platelets have a central role in arterial thrombosis
  Heart attack (myocardial infarction)
  Stroke
  Sudden death

Question 2

Explain Platelet Shape Change?

Answer 2

Activation leads to Shape change
Smooth discoid leads to spiculated + pseudopodia
Increases surface area
Increases possibility of cell-cell interactions

Question 3

What is Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor?

Answer 3

• On surface of platelet
  50,000 to 100,000 copies on resting platelet
• Platelet activation
  Increases number of receptors
  Increases affinity of receptor for fibrinogen
  Fibrinogen links receptors, binding platelets together (platelet aggregation)

Also known as integrin aIIbb3

Question 4

What is platelet aggregation?

Answer 4

Mediated by GPIIb/IIIa activation (final common pathway)
Cross linking of platelets by fibrinogen

Question 5

What is Platelet Adhesion?

Answer 5

Collagen and VWF exposed when endothelial layer damaged
Platelet adhesion mediated by GPIb, 21 and GPVI

Question 6

What are platelet granules?

Answer 6

Mediators of vessel response to injury
Inflammatory mediators released from a granules

Question 7

Summarise amplification pathways and inhibitors?

Answer 7

Thromboxane A2 – Aspirin
P2Y12 receptors – Clopidogrel, Prasugrel, Ticagrelor

Question 8

What is Hemostasis?

Answer 8

Blood loss prevention

Question 9

How is a platelet plug formed? (First Step)

Answer 9

Endothelial Injury

• Nerves/Smooth muscle cells detect an injury and trigger reflexive contractions of vessels.
• This causes a decrease in blood flow.
• Also nitric oxide is secreted and prostaglandis stops.
• Secretion of endothelin begins and contractions continue.

Question 10

What is the second step of platelet plug formation?

Answer 10

Exposure

• Damage to endothelial cells exposes collagen
• Damaged cells release Von Willebrand factor (binds to collagen)

Question 11

What is the third step of platelet plug formation?

Answer 11

Adhesion

• GP1B surface proteins on platelets bind to Von Willebrand Factor

Question 12

What is the fourth step of platelet plug formation?

Answer 12

Activation

• Platelet changes shape (forms arms to grab other platelets)
• Releases more Von Willebrand factor, Serotonin, Calcium, ADP, Thromboxane A2 result in GPIIB/IIIA expression
• ADP, Thromboxane A2 results in GPIIB/IIIA expression

Question 13

What is the last step of platelet plug formation?

Answer 13

Aggregation

• GPIIB/IIIA binds to fibrinogen, links platelets
  Causing the formation of a Platelet Plug

Question 14

What is the extrinsic pathway?

Answer 14

• Trauma damages blood vessels, exposes cells under endothelial layer
• Tissue factor (factor III) embedded in membrane
• Factor VII in blood binds to tissue factor,
  Caclcium leads to VIIa - TF complex

Question 15

What happens in the Intrinsic Pathway?

Answer 15

• Circulating factor XII contacts negatively charged phosphates on platelets/subendothelial collagen leading to Factor XIIa
• Factor XIIa cleaves Factor XI leading to Factor XIIa
• Factor XIa + Calcium cleaves Factor IX leading to Factor IXa
• Factor IXa + Factor VIIIa (binds to Von Willebrand factor) + Calcium, enter the common pathway

Question 16

What happens in the Common Pathway?

Answer 16

• Factor X is cleaved - Factor Xa
• Factor Xa cleaves factor V - Factor Va
• Factor Xa + Factor Va + Calcium - Prothrombinase Complex
• Prothrombin (factor II) - thrombin (factor IIa)
• Thrombin activates platelets, cofactors (V,VIII,IX), cleaves fibrinigen, stabilising factor (factor XIIIa + calcium, cross-links in mesh)

Question 17

What Coagulation Tests are used?

Answer 17

• Prothrombin Time (PT): Tests extrinsic pathway
• Activated Partial Thromboplastin Time (aPTT): Tests Intrinsic Pathway

Question 18

How does Vitamin K regulate Blood Coagulation?

Answer 18

Converts Coagulation factors into mature forms

Question 19

How does Vitamin K regulate Blood Coagulation?

Answer 19

Converts Coagulation factors into mature forms