Platelet Biochemistry

Question 1

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

Platelet shape change

Answer 2

When platelets are activated they change shape

Smooth discoid —> spiculated + pseudopodia
Increases surface area
Increases possibility of cell-cell interactions

Question 3

Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor

Answer 3

On surface of the platelet ^receptor is expressed
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

Platelet receptors

Answer 4

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

Question 5

Platelet activation mechanisms

Answer 5

Receptors are activated by substances- eg GPV1 is activated by collagen

This leads to:
Shape change
Cross-linking of GPIIb/IIIa
Platelet aggregation

Question 6

Aspirin

Answer 6

Aspirin inhibits an amplification pathway

Anti-platelet drug

Question 7

Hemostasis

Answer 7

Blood-loss prevention

Question 8

First 2 hemostasis steps

Answer 8

Platelets clump
Form plug around injury site in five steps

Question 9

1) Endothelial injury

Answer 9

Nerves, smooth muscle cells detect injury

Trigger reflexive contraction of vessel (vascular spasm) decreasing blood flow

Secretion of nitric oxide, prostaglandins such as prostacyclin stop (these are vasodilators)

Secretion of endothelin 1 begins leading to further contraction

Question 10

2) Exposure

Answer 10

Damage to endothelial cells exposes collagen

Damaged cells release Von Willebrand factor (binds to collagen)

Question 11

3) Adhesion

Answer 11

GPIIb/IIIa surface proteins on platelets bind to Von Willebrand factor

Question 12

4) Activation

Answer 12

Platelet changes shape (forms arms to grab other platelets), releases more Von Willebrand factor, serotonin, calcium, ADP, thromboxane A2 (positive feedback loop)

ADP, Thromboxane A2 results in GPIIb/IIIa expression (cross bridge with each other)

Question 13

5)Aggregation

Answer 13

GP11B/IIIA binds to fibrinogen, links platelets

Forms platelet plug

Question 14

Secondary hemostasis

Answer 14

Last 2 hemostasis steps: clotting factors activate fibrin, build fibrin mesh around platelet plug

Begins with either extrinsic/intrinsic pathway, factor X activation leading to coagulation cascade (common pathway)

Question 15

Extrinsic pathway

Answer 15

1) severe Trauma causes Tissue factor (factor III), embedded in membrane of exterior cells (cellls that aren’t part of vessel) to leak out

2) Factor VII in blood binds to tissue factor and Calcium leading to factor VIIa Complex

3–>7–>10 (10 is common pathway)

Question 16

Intrinsic pathway

Answer 16

1) Circulating factor XII contacts negatively charged phosphates on platelets/sub-endothelial collagen leading to factor XIIa

2) Factor XIIa cleaves factor XI leading to factor XIa

3) Factor XIa and calcium cleaves factor IX leading to factor IXa

4) Factor IXa and factor VIII (binds to Von Willebrand factor) and calcium therefore enter the common pathway

12 to 11 to 9 to 8 to 10 (10 is common pathway)

Question 17

Common pathway

Answer 17

1) Factor X is cleaved activates factor Xa

2) Factor Xa cleaves factor V leading to factor Va

3) Factor Xa + factor Va + calcium leads to complex
- Prothrombin (factor II) leads to thrombin (factor (IIa)

4) Thrombin activates platelets, cofactors (V, VII, IX); cleaves fibrinogen, stabilising factor (leading to factor XIIa + calcium leading to cross links in mesh)
Factor I is fibrinogen which is then activated to fibrin

Question 18

Coagulation tests

Answer 18

Prothrombin time (PT)A: tests extrinsic pathway

Activated partial thrombosplatin time (aPTT): tests intrinsic pathway

Question 19

Hydrolysing the secondary platelet plug

Answer 19

tPa hydrolyses plasminogen to plasmin

Plasmin eats the fibrin which results in deactivation of fibrin to fibrinogen

The remaining primary platelet plug then falls apart as there is no fibrin to maintain its stability

Question 20

Vitamin K dependant clotting factors

Answer 20

10

9

7

2

Remember as 1972 (with 0 subscript of 1)