Anticoagulants

Question 1

Haemostasis is a balance of

Answer 1

Thrombosis and bleeding

Question 2

Bleeding defects can be caused by

Answer 2

Platelet defect or coagulating defects

Question 3

Function of platelets

Answer 3

Clotting
Immune activation
Wound healing

Question 4

Haemostasis mechanism

Answer 4

Reflex vasoconstriction to prevent further blood loss

Primary - thrombus formation (mainly consist of platelets) - occurs within 5 mins

Secondary - stabilisation of clot by fibrin (within 10 mins)

After formation of clot - retraction of clot to prevent occlusion

Both occur simultaneously

Question 5

People with anaemia are more likely to have bleeding problems, why?

Answer 5

Normally platelets are pushed towards vessel walls due to RBCs (exacerbated in smaller vessels due to fahraeus effect) and hence platelets are less likely to encounter the vessel wall

Question 6

EC normally secrete antithrombotic substances such as

Answer 6

PG, NO

Question 7

Warfarin and heparin are

Answer 7

Anticoagulants

Question 8

Antithombotic (antiplatelet) drugs

Answer 8

P2Y12 inhibitor - clopidogrel, prasugrel, tricagrelor (reversible)
Anti-thrombin III - binds to thrombin receptors PAR1/4
GPIIb/IIIa inhibitor - Abcitimab (mediates platelet aggregation)
COX inhibitor - aspirin (irreversible inhibition); blood thinning

Question 9

Anticoagulants

Answer 9

Heparin and warfarin

Question 10

Warfarin MoA

Answer 10

Vitamin K antagonist
Vit K is important in F2/7/9/10 PTM
Warfarin prevent PTM of these coagulating factor hence inhibiting clotting
Small therapeutic window and requires monitoring due to S ISOform metabolism. By CYP2C9 is sensitive to genetic variation

Question 11

Heparin MoA

Answer 11

Binds to antithrombin III (natural inhibitor of thrombin and FXa)
Short half life
Reversible by giving protamine sulphate
Often surgery choice

Question 12

P2Y12 binds to ADP and activate which G protein cascade to achieve what

Answer 12

Gi - decrease cAMP and facilitate aggregation

Question 13

P2Y1 receptor is coupled to what receptor and results in what

Answer 13

Gq - PLC IP3 pathway which facilitates platelet shape change and aggregation

Question 14

Activation of GPVI receptor on platelets activate

Answer 14

Dense tubular system which facilitates degranulatiin

Question 15

LDL Contains apoprotein which is similar to what

Answer 15

Plasminogen

Question 16

Why does hyperlipidaemia increase thrombosis risk?

Answer 16

1) atherosclerotic plaque formation 2) Apoprotiens are similar to plasminogen hence compete for receptor and decrease plasmin production

Question 17

60-70% of circulating cholesterol is

Answer 17

LDL