Haemostasis, Anti-Platelets & Anti-Thrombotics

Question 1

Define haemostasis

Answer 1

The arrest of bleeding

Question 2

What are the 6 main stages of haemostasis?

Answer 2

1- Injury to the blood vessel wall

2- Recruitment and activation of blood platelets (PRIMARY HAEMOSTATIC RESPONSE)

3- Blood clotting (SECONDARY HAEMOSTATIC RESPONSE)

4- Clot retraction (consolidation of fibrin plug)

5- Tissue regeneration

6- Fibrinolysis (breakdown of fibrin)

Question 3

What are the four main functions of vascular endothelium?

Answer 3

Regulates smooth muscle tone

Regulates permeability of the vessel wall

Provides defence against pathogens

Provides an anti-thrombotic surface to prevent clot formation

Question 4

What are the two types of granules contained within the cytoplasm of platelets?

Answer 4

ALPHA GRANULES - Contain clotting proteins and platelet derived growth factor (PDGF)

DENSE GRANULES - Contain ADP, ATP, calcium ions, serotonin and enzymes that produce thromboxane A2 and fibrin stabilising factor etc

Question 5

What occurs during platelet plug formation?

Answer 5

Platelets adhere to exposed connective tissue in the vessel wall and release granules…

ADP and thromboxane A2 activates other nearby platelets

Serotonin and thromboxane A2 induce vasoconstriction

ADP makes the other platelets ‘sticky’ - by stimulating the expression of glycoprotein IIb/IIIa receptors that promote platelet aggregation

Question 6

Define the term thrombosis?

Answer 6

Inappropriate formation of a haemostatic plug in the absence of bleeding (e.g as a result of damage to the vascular endothelium secondary to hypertension, inflammation, smoking etc)

Question 7

What type of thrombus is referred to as a ‘white’ thrombus?

Answer 7

An arterial thrombus - as they often mainly consist of platelets and leukocytes in a mesh of fibrin (these are mainly associated with atherosclerotic disease)

Question 8

What type of thrombus is referred to as a ‘red’ thrombus?

Answer 8

Venous thrombus - As they consist mainly of erythrocytes and fibrin (e.g in deep venous thrombosis)

Question 9

What type of drug is used to prevent the formation of a ‘white’/arterial thrombus?

Answer 9

Anti-Platelets

Examples:
Aspirin

GPIIb/IIIa Receptor Antagonists - Tirofiban, Eprifibatide, Abciximab

P2Y 12 Receptor Antagonists - Clopidogrel, Prasugrel, Ticlodipine

Phospodiesterase Inhibitor - Dipyridamole

Question 10

What type of drug is used to prevent the formation of a ‘red’/venous thrombus?

Answer 10

Anti-Coagulants

Examples of oral anti-coagulants:
Warfarin
Direct Factor Xa Inhibitors - Apixaban, Rivaroxaban
Direct Thrombin Inhibitors- Dabigatran Etexilate

Examples of intravenous anti-coagulants:
Heparin
Low Molecular Weight Heparins - Enoxaparin, reviparin

Question 11

What are the three aspects of Virchow’s Triad?

Answer 11

Virchow’s Triad describes the three main factors that contribute to thrombosis (mostly associated with venous thrombosis), which are…

Injury to the Vessel Wall/ Endothelial Lining - Which can occur as a result of endothelial damage (induced by smoking, inflammation etc), trauma, surgery and/or catheterisation

Hypercoagulabilty - Which can occur due to deficiencies of anti-coagulant proteins, dehydration, oral contraceptive use and/or hormone replacement therapy

Stasis - As a result of immobility (e.g due to paralysis, bed rest, sedentary lifestyle, long haul flights etc)

Question 12

Describe the role of nitric oxide in vascular health?

Answer 12

Nitric oxide causes vasodilation, inhibits platelet aggregation and reduces vascular smooth muscle proliferation, promoting vascular health