Cardio - Thrombosis, anticoaguants, antiplatelets

Question 1

what kind of thrombus is an arterial thrombus and how are they treated?

Answer 1

white thrombus - platelets in a fibrin mesh

treated with antiplatelets

Question 2

what kind of thrombus is a venous thrombus and how are they treated?

Answer 2

red thrombus - white head, red tail, fibrin rich

treated with anticoagulants

Question 3

where an embolus from an arterial thrombus likely to lodge?

Answer 3

artery in brain or other organ

Question 4

where is an embolus from an arterial thrombus likely to lodge?

Answer 4

lungs (PE)

Question 5

what is the role of vitamin K in blood clotting?

Answer 5

Required in its reduced form as an essential cofactor for the carboxylase enzyme that mediates carboxylation of clotting factors II, VII, IX and X to their active forms that act as serine proteases

Question 6

how does warfarin work?

Answer 6

blocks action of Vitamin K reductase which reduces viamin K to its reduced form rendering clotting factors II, VII, IX and X inactive
Slow onset over 2-3 days

Question 7

what are the risks with warfarin?

Answer 7

low therapeutic index
delay to maximum effect
effect must be monitored regularly via INR

Question 8

how can warfarin overdose be treated?

Answer 8

Vit K1 (as phytomenadione)
concentrate of plasma clotting factors

Question 9

what increases warfarin risk?

Answer 9

liver disease
high metabolic rate
drug interactions (antiplatelets etc)

Question 10

what lessens warfarin risk of haemorrhage (increases thrombosis risk)?

Answer 10

pregnancy
hypothyroidism
Vit K consumption
Drug interactions (ones that increase warfarin metabolism rate)

Question 11

what is antithrombin III?

Answer 11

inhibitor of coagulation which neutralises serine proteases (active clotting factors) in coagulation cascade by binding to active site in 1:1 ratio

Question 12

how does heparin work?

Answer 12

binds to antithrombin III increasing its affinity for serine proteases clotting factors increasing rate of inactivation

Question 13

what do LMWHs do?

Answer 13

inhibit factor Xa (prothrombinase) but not thrombin (IIa)

Question 14

how is heparin administered?

Answer 14

LMWH = Subcutaneous
Heparin = IV or SC
heparin dose determined via in vitro clotting test

Question 15

how is LMWH eliminated?

Answer 15

via renal excretion

therefore heparin is preferred in renal failure as it has a different elimination pathway

Question 16

give some examples of LMWHs

Answer 16

enoxaparin
dalteparin
fondaparinux and idrabiotaparinux are similar to LMWH

Question 17

what are the risks of heparin and LMWH?

Answer 17

haemorrhage (treat with protamine sulfate IV and stopping drug)
osteoporosis (long term)
hypoaldosteronism
hypersensitivity reactions

Question 18

how does aspirin work?

Answer 18

irreversibly blocks COX in platelets preventing TXA2 synthesis
blocks COX in endothelial cells inhibiting production of antithrombotic prostaglandin I2 (PGI2)

Question 19

why does aspirin therapy shift balance in favour of antithrombotic effect?

Answer 19

endothelial cells can synthesise new COX enzymes while enucleate platelets cant
TXA2 synthesis doesn’t recover for 7-10 days until affected platelets are replaced

Question 20

what is the main adverse affect of aspirin?

Answer 20

GI bleeding and ulceration

Question 21

how does clopidogrel work?

Answer 21

links to P2Y12 receptor via disulphide bond causing irreversible inhibition

Question 22

when is clopidogrel used?

Answer 22

if aspirin intolerant

combined with aspirin for combined synergistic effect

Question 23

when is Tirofiban used?

Answer 23

short term IV to prevent MI in high risk unstable angina

Question 24

what is the fibrinolytic cascade?

Answer 24

Plasminogen > plasmin catalyses breakdown of fibrin to fibrin fragments
exists endogenously and opposes coagulation cascade

Question 25

name some fibrinolytics?

Answer 25

streptokinase

Alteplase and Duteplase

Question 26

when are fibrinolytics used and what is the risk?

Answer 26

used to reopen artery in MI

risk of haemorrhage (controlled via tranexamic acid)

Question 27

what are the pros and cons of orally active inhibitors (eg - dabigatran etexilate)?

Answer 27

pros
- convenient administration
- predictable degree of anticoagulation
cons
- no agent to treat haemorrhage in overdose
used to prevent thrombosis in hip/knee replacement

Question 28

what does warfarin block?

Answer 28

factors X and II (prothrombin)

Question 29

what does rivaroxiban block?

Answer 29

factor Xa

Question 30

what do heparin, LMWH and fondaparinux block?

Answer 30

factor Xa via antithrombin III

Question 31

what does dabigatran block?

Answer 31

factor IIa

Question 32

what does heparin block as well as factor Xa?

Answer 32

IIa via antithrombin III