Antithrombolytic & Antiplatelet Therapy

Question 1

Understand the general features of thrombus formation and clotting cascades

Answer 1

Platelet aggregation
Activation of coagulation –> thrombin –> fibrinogen –> fibrin –> fibrin polymers
Clotting factors

Question 2

List some anti clotting agents (ACAs)

Answer 2

Warfarin
Heparin
Xa or thrombin inhibitors

Question 3

Describe the mechanism of action and ADRs of warfarin

Answer 3

MOA - competitively inhibits production of vitamin K dependent clotting factors (2, 7, 9, 10) and proteins C&S
Stops conversion to active reduced form
ADRs - increased risk of bleeding/bruising (intracranial, epistaxis, GI), teratogenesis

Question 4

Describe the therapeutic uses of warfarin and understand the practical importance of warfarin PKs in titrating doses

Answer 4

Uses - DVT, PE, AF, mechanical prosthetic valves, thrombophilia
PKs - slow onset of action and duration, easily absorbed in gut, heavily protein bound by albumin
Crosses placenta = teratogenic in first trimester
*stop 3 days before surgery

Question 5

Explain the important ADRs and DDIs with warfarin and their particular importance in affecting therapeutic activity

Answer 5

ADRs - bleeding/bruising e.g. intracranial, epistaxis, GI loss
DDIs:
Potentiate (increased INR) - inhibit hepatic metabolism, inhibit platelet function (aspirin), decrease absorption of vitamin K from gut bacteria (cephalosporins)
Inhibit (decrease INR) - anti epileptics, rifampicin, St John’s Wort

Question 6

Describe, with reference to the INR, the steps in managing reversal of warfarin action

Answer 6

Parenteral vitamin K (slow)

Fresh frozen plasma (fast)

Question 7

Recognise the two major molecular heparin groups and appreciate their differing PKs, sites and mechanisms of action and therapeutic uses

Answer 7

Unfractionated heparin - given IV due to poor GI absorption, binds to AT3 (increased activity) –> inactivated IIa, Xa
Low weight heparin - smaller SA, given SC, only binds to AT3 –> inactivated Xa ONLY
Low weight - long half life, more predictable dose response, less likely to cause thrombocytopenia, rapid onset and offset
Uses - peri-operative, immobility, DVT, PE, AF, ACS, pregnancy

Question 8

Describe administration and monitoring of heparin, the most serious ADRs and how to reverse heparin effects

Answer 8

Administration - IV (unfractionated), SC (low weight)
ADRs - osteoporosis, bleeding/bruising, heparin induced thrombocytopenia
Reversal - protamine sulphate

Question 9

List some antiplatelet agents

Answer 9

Aspirin
Dipyridamole
Clopidogrel
Glycoprotein IIb/IIIa inhibitors

Question 10

Describe the mechanism of common anti platelet drugs

Answer 10

Aspirin - irreversibly inhibits COX1 and thromboxane A2
Dipyridamole - phosphodiesterase inhibitor
Clopidogrel - ADP antagonist, inhibit platelet aggregation
Glycoproteins IIb/IIIa inhibitors - decrease platelet cross linking by fibrinogen

Question 11

List some common thrombolytics

Answer 11

Streptokinase - bacterial protein, antigenic, cannot be used twice
Aleplase - recombinant tPa, not antigens

Question 12

Describe the mechanisms of thrombolytic therapy

Answer 12

Plasminogen activators

Plasmin cleaves fibrin

Question 13

Name the main conditions for which thrombolytics are used

Answer 13

Acute MI
Stroke
DVT –> PE

Question 14

List the main ADRs of thrombolytics and the conditions that may increase ADR risk

Answer 14

ADRs - haemorrhage (treat with blood transfusion, tranexamic acid) in brain, GIT, coagulation defects
Contraindications - active peptic ulcer, recent trauma/surgery

Question 15

Describe the main factors involved in normal and abnormal haemostasis, referring to Virchow’s triad

Answer 15

Hypercoagulability - genetic/acquired
Endothelial damage - atheroma/hypertension/toxins
Stasis - immobility/cardiac abnormality