Arterial Thrombosis

Question 1

Vasculature

Answer 1

• pressurised vascular system is required to perfuse all tissues
• so a hole in vasculature means this pressure drives blood out

Question 2

Treatments for arterial thrombosis

Answer 2

• relieve pain = nitrates, opioids, beta-blockers
• reperfuse = thrombolytics, precutaneous coronary intervention/coronary angioplasty, bypass surgery
• stop thrombosis = anti-platelet or anti-coagulant agents

Question 2

Haemostatic system

Answer 2

decreases blood loss
- platelets = cell-based system
- coagulation = protein-based system

coagulation:
- thrombin production
- thrombin forms fibrin
- fibrin forms a mesh
- clot forms outside of vessel

Question 3

Anti-thrombotics - when to use

Answer 3

before - prevent thrombosis, perhaps in at risk patients (primary intervention)
during ACS - particularly during PCI
after = prevent new thrombi (secondary intervention)

Question 3

Arterial thrombosis

Answer 3

atherosclerotic plaque –> platelet aggregation –> coagulation –> thrombus

thrombus = clot in the lumen of the vessel

acute coronary syndrome = sudden onset of pain caused by:
- thrombus partly blocking coronary vessel
- or completely blocking vessel

causes decreased blood flow to the cardiac muscle

Question 4

Platelet structure

Answer 4

• dense core granules
• open canalicular system
• alpha granules
• mitochondria
• no nucleus or DNA

Question 5

Role of the open canalicular systme

Answer 5

internal structure likely provides reservoir of internal membrane
- detect signals
- adhere to sites
- make changes and adhere to platelets

Question 6

Platelets and in tact vs damaged blood vessels

Answer 6

in tact blood vessels inhibit platelets
- via NO and PGI2
- conceals subendothelial matrix

platelets adhere to damaged vessels
- exposed subendothelial matrix (collagen, elastin, laminin)
- vWF and fibrinogen are plasma-borne adhesion molecules

Question 7

Platelet adhesion

Answer 7

interaction between GPIb (platelet) and vWF (plasma)
- can form under high shear
- activation-independent
- fast dissociation
- results in weak intracellular signalling

interaction between GPVI and collagen
- direct interaction
- low affinity
- activation-independent
- results in strong intracellular signalling

interaction between GPIIb/IIIa and vWF
- high affininty
- activation-dependent
- triggers more intracellular signalling

Question 8

Bernard Soulier syndrome

Answer 8

lack of (or non-functional) GPIb on platelets to interact with vWF

Question 9

von Willebrand’s disease

Answer 9

lack of vWF in plasma to interact with GPIb on platelets

Question 10

Glanzmann’s thrombasthenia

Answer 10

lack of (or non-functional) GPIIb/IIIa on platelets to interact with vWF

Question 11

vWF

Answer 11

von Willebrand’s factor

Question 12

Platelet activation

Answer 12

• once adhered, massive increase in platelet surface area
• using internal membrane system
• secretion of ADP, ATP and 5-HT
• thromboxane synthesis
• integrin activation

Question 13

Platelet activation - secretion

Answer 13

• Hermansky-Pudlack syndrome
• inhibited by P2Y12 antagonists

Question 14

Platelet activation - adhesion

Answer 14

• Glanzmann’s thrombasthenia
• inhibited by GPIIb/IIIa antagonists

Question 15

Platelet activation - thromboxane synthesis

Answer 15

• inhibited by aspirin

Question 16

Unstable angina

Answer 16

• partly blocks vessel
• ischaemia

Question 17

Non-ST segment- elevated myocardial infarction (NSTEMI)

Answer 17

• partly blocks
• ischaemia and necrosis

Question 18

ST segment-elevated myocardial infarction (STEMI)

Answer 18

• completely blocks
• ischaemia and necrosis