Blood Coagulation, Platelet Aggregation, Fibrinolysis

Question 1

What is haemostasis

Answer 1

The balance between clotting and bleeding.
The balance between normal blood flow and preventing blood loss.
Complex interaction between:
Blood vessels - vascoconstricion
Platelets
Coagulation and clotting factors - inhibitors
Fibrinolysis

Question 2

What is an embolous

Answer 2

A fragment or whole thrombus that detached from the vessel wall and travels through the vessel. It can block small blood vessels in the pulmonary/ cardiac/ CNS circulation.

Question 3

What does an embolous cause

Answer 3

Pulmonary embolism
Myocardial infarction
Stroke

Question 4

How does a thrombus form

Answer 4

When there is not enough blood/ oxygen flow to a tissue the fibrin framework incorporates platelets or other blood cells and they become trapped. It is attached to the vessel wall which then impacts on blood flow and reduces tissue perfusion.

Question 5

What are the types of thrombus

Answer 5

Venous thrombosis- where coagulation has a major role

Arterial thrombosis- where platelet aggregation plays the major role (coagulation included)

Question 6

How do you modify a thrombosis

Answer 6

. Modify coagulation (v)
. Modify platelet aggregation (a)
. Modify clot thrombous break down- after prevention fails

Question 7

What is an example of an anti- coagulant

Parin

Answer 7

Heparin.
We have a natural supply.
It is present in the liver lungs and mast cells as a natural anticoagulant.

VENOUS

Question 8

What does heparin do

Answer 8

. Activated AT
. AT forms complexes with activated clotting factors (thrombin factors xa) and inactivated them.
. Heparin then increases the rate of complex formation
. Stops thrombous

Question 9

What are the issues with heparin

Answer 9

It’s poorly absorbed when administered orally but can be given intravenously or subcutaneously.
There is a risk of haemorrhage- when mild stop when severe protea mine sulphate needed to stop heparin AT effect

Question 10

What is an example of a drug that is an oral anticoagulant

Answer 10

Warfarin.

Question 11

What does warfarin do

Answer 11

.Related in structure to vitamin K.
.Antagonises vit k’s role in formation of various clotting factors (2,7,9)
.stops conversion of precursors of these to active factors- promotes coagulation.

Question 12

What are the problems with warfarin

Answer 12

It's slow to work- 3 days
Need to give heparin first to work.
Variation in half life between clotting factors. 
Influenced by vit k 
It interacts with many things
Monitored using INR (h/w) 
Risk of haemorrhage (m stop s vit k/ clotting f/ blood) 
Teratogenic (avoid preg)

Question 13

What is rivaroxaban

Answer 13

. Oral fxa inhibitor

. Prevents both venous and arterial thromboembolic disorders

Question 14

What are the benefits of rivaroxaban

Answer 14

. Fixed dose
. No need for routine monitoring
. Effective in both venous and arterial thromboembolic disorders
. Potentially can replace warfarin

Question 15

What is dabigatran

Answer 15

.An oral thrombin inhibitor

. Used to prevent venous thrombosis in orthopaedic surgery without increasing bleeding risk

Question 16

What are the benefits of dabigatran

Answer 16

. Fixed dose
. No routine monitoring
. Effective in preventing venous thrombosis in orthopaedic surgery with no increased risk of bleeding
. Potentially replace warfarin

Question 17

How does a clot form

Answer 17

Damage to the vessel
Then collagen is exposed
The platelets then bind and are activated
There’s an increase in txa2 synthesis
This leads to an increase in GPIIB / IIIA receptor expression on the platelets
The platelets hen aggregate

Question 18

What factors affect aggregation

Answer 18

. Synthesis of a thromboxane in platelets (reduce)
. cAMP levels in platelets (increase)
. Glycoprotein IIb IIIA receptors in platelet (reduce)

Question 19

What is an example of an anti platelet drug which reduces synthesis of thromboxane within the platelets

Answer 19

Asprin

Question 20

What does Asprin do

Answer 20

. Blocks COX enzyme to reduce txa2 synthesis.
. Aggregation is reduced until new platelets are made. 7-10.
. Low dose needed to avoid enzyme endothelium.
. Alters the balance between platelet txa2 and endothelial PGI2

Question 21

What is an example of an anti platelet drug which raises cAMP levels in the platelet

Answer 21

Dipyridamole

Question 22

What does dipyridamole do

Answer 22

. Stops PDE enzyme
. Prevents cAMP breakdown in platelets
. Decreases platelet aggregation
. Blocks he intake of adenosine into platelets, red cells and endothelial cells 
. Stops TXA2 synthesis

Question 23

What is an example of a drug which reduces the glycoprotein IIb/ IIIa receptors in a platelet

Answer 23

Clopidogrel

Question 24

How does Clopidogrel work

Answer 24

. Inhibits platelet receptors
. It’s irreversible and specific
. It stops ADP receptor
. It blocks the activation of glycoprotein IIb/IIIa pathway

Question 25

Which drug synthesises thromboxane A2 within platelets

Answer 25

ASPRIN- reduces

Question 26

Which drug works on cAMP levels I platelets

Answer 26

Dipyridamole- increases

Question 27

Which drug acts on glycoprotein IIb/IIIa receptors on platelet

Answer 27

Clopidogrel- reduce

Question 28

What do fibrinolgic drugs do

Answer 28

. Dissolve pre existing clots/ thrombous 
. Used in emergency fast acting
. Danger of haemorrhage 
. Danger of emboli
. Given IV or intracorony

Question 29

What is an example of a fibrinolytic drug

Ase

Answer 29

. Streptokinase

Question 30

What does anteplase do

Answer 30

. Works inside thrombous were fibrin strands are bound to plasminogen
. Binds to the complex
. Converts inactive plasminogen to plasmin.
. Plasmin then digests the fibrin
. Clot dissolved

Question 31

What is thrombosis

Answer 31

The formation of a thrombus within a blood vessel.

It’s initiated by the pooling of blood in veins due to slow flow or damaged vessels or atheromatous plaques.