6.2 anti platelets, anticoagulants and thrombolysis

Question 1

when is venous thrombosis likely to occur and what does it look like?

Answer 1

associated with stasis of blood and/or image to the veins = less likely to see endothelial damage

high red blood cell and fibrin contents low platelet content and evenly distributed

Question 2

when is arterial thrombosis likely to occur and what does it look like?

Answer 2

usually forms at site of atherosclerosis forming a plaque rupture

lower fibrin content and much higher platelet count

Question 3

why would the type of thrombus indicate a different treatment?

Answer 3

lower platelet count red venous thrombus = use anticoagulants e.g heparin and warfarin

higher platelet count arterial thrombi = antipatelet and fibrinolytic drugs

Question 4

how does aspirin work?

Answer 4

it is a COX 1 inhibitor = reduces the amount of thromboxane and thus inhibits platelet aggregation, with irreversible effects

good for platelet rich thrombi e.g arterial thrombi

higher doses will have a counter effect so need to get it right

Question 5

what are the side effects of aspirin?

Answer 5

bleeding time prolonged e.g haemorrhage stroke and GI bleeding (peptic ulcers)

Question 6

how do clopidogrel and prasugrel work?

Answer 6

inhibit platelet aggregation as a P2Y/ADP receptor antagonist

reduce morbidity and mortality post thromboembolic stroke
reduce secondary events post MI with asprin

useful in prophylaxis in patients intolerable to aspirin

Question 7

how does abciximab work?

Answer 7

irreversibly blocks GPIIb/IIIa receptors preventing fibrinogen binding

given IV, also a glycoprotein

Question 8

how does dipyridamole work?

Answer 8

inhibits cellar reuptake of adenosine = increased plasma adenosine = inhibits platelet aggregation via a2 receptors

will also inhibit photodiesterase = prevent cAMP and cGMP degradation = inhibits GPIIb/IIIa expression

Question 9

what are the side effects of dipyridamole?

Answer 9

flushing and headache, hypersensitivity

Question 10

what is the role of plasminogen activators in thrombolysis?

Answer 10

convert plasminogen to plasmin, which helps fibrinolysis of a fibrin clot

Question 11

what is the role of streptokinase in thrombolysis?

name 2 other drugs which work in the same way as streptokinase.

Answer 11

activates plasminogen

streptokinase similar drugs include:

• alteplase
• reteplase

Question 12

what is the role of tranexamic acid in thrombolysis?

Answer 12

aids fibrinolysis of the fibrin clot into degradation products

Question 13

why can’t streptokinase be given repeatedly?

Answer 13

its antigenic aka will trigger an immune response

therefore, given in short infusions and less commonly used than the others

Question 14

what are anticoagulant drugs?

Answer 14

prevent thrombus formation and thrombus growing

Question 15

how can vitamin K agonists prevent clotting? give an example

Answer 15

vit K agonists e.g warfarin (half life 36-48hrs)

inhibit production of vit K dependant clotting factor and stops conversion of vitamin k to active reduced form (inhibits reductase)

so, can’t do hepatic synthesis of clotting factors e.g prothrombin and factor 7

Question 16

when is warfarin used therapeutically?

Answer 16

DVT prophylaxis and treatment
PE prophylaxis and treatment
AF with high risk of stroke
Protein S and C deficiency 
following orthopaedic surgery (stasis)

Question 17

what are the properties of warfarin?

Answer 17

slow onset of action = need heparin cover if anticoagulation is needed immediately

good GI absorption and taken orally

highly protein bound (remember displacement issues)

activity highly variable in individuals - monitor INR

Question 18

what is INR?

Answer 18

An INR test measures how long it takes for your blood to clot. It is primarily used to diagnose unusual bleeding, blood clots, and monitoring people being treated with warfarin (an anti-clotting treatment).

A low INR result means your blood is ‘not thin enough’ or coagulates too easily and puts you at risk of developing a blood clot.

A high INR result means your blood coagulates too slowly and you risk bleeding.

normal INR range = 1-1.5

Question 19

why should warfarin be watched In pregnancy?

Answer 19

it can cross the placenta
so avoid in
1st trimester - tetrogenic
3rd trimester - brain haemorrhage

Question 20

what is warfarin response governed by?

Answer 20

CYP2C9,
other drugs,
vit K intake,
coagulation proteins

Question 21

how should warfarin be monitored?

Answer 21

factor 7 is most sensitive to vit k deficiency so used in prothrombin time - standardised against control plasma = INR test

Question 22

what is the main ADR of warfarin and how can this be treated?

Answer 22

main ADR
- bleeding

most effective treatment

• antidote of vit k1
• prothrombin complex iv
• fresh frozen plasma
• stop warfarin

Question 23

what are warfarins main drug-drug interaction ?

Answer 23

• inhibition of hepatic metabolism, especially CYP2C9, amiodarone, clopidogrel, alcohol, quinolone, metronidazole
• inhibit platelet function (no real reaction with aspirin but blood will be extra thin = monitor carefully)
• taken with some antibiotics, will affect vitamin K ability to be eliminated and eliminate gut bacteria
• NSAIDS inhibit vit k absorption and increase INR, also displace warfarin from plasma albumin
• acceleration of warfarin metabolism e.g barbiturates, rifampicin phenytoin, St johns wort. will all decrease INR

Question 24

give an example of a paraenteral anticoagulant

Answer 24

e.g heparins
they inhibit the action of coagulation factors
heparin produced naturally in mast cells and vascular endothelium and extracted for clinical age

Question 25

how do unfractioned heparins work?

Answer 25

causes conformation change and increased activity of antithrombin
also inhibits IIa through binding to it and ATII, as well as Xa

unfractioned = low bioavailability, short half life (30mins),, IV

Question 26

how do LMWH work?

Answer 26

LWMH = longer Half life (2hrs), high bioavailability, more predictable host response, doesn’t inactivate thrombin IIa and target Xa specifically. less likely than UFH to cause thrombocytopenia, also injected

Question 27

name 2 low molecular weight heparins

Answer 27

bempiparin

dalteparin

Question 28

what is the difference between unfractioned and low molecular weight heparins?

Answer 28

UFH

• non linear dose reponse
• variable bioavaliability
• metabolised via plasma protein binding, depolymerisation, desolation
• unpredictable response
• IV administration
• 30mins low dose 2hr high dose half life

LMWH

• predictable dose response
• bioavaliability 90%
• rapid liver metabolism/slower renal excretion
• generally no monitoring
• subcutaneous injection administration
• 2hr half life

Question 29

when are heparins used?

Answer 29

• DVT, PE and AF administered prior to warfarin due to its quicker onset
• acute coronary syndrome post MI/NSTEMI, unstable angina
• during pregnancy as doesn’t cross placenta
• prevention of venous thromboembolism
• preoperative prophylaxis with LMWH for several days

Question 30

what are the ADRs of heparin?

Answer 30

bruising and bleeding

• intracranial
• at site of injection
• GI
• epistaxis

hepatic and renal compromise
elderly
carcinoma

heparin induced thrombocytopenia
can lead to thrombosis as more platelets activated alternative anticoagulation initiated and reversal of heparin lab assay will confirm HIT

Osteoporosis is rare

Question 31

how can you reverse the effects of heparin?

Answer 31

protamine sulphate dissociates heparin from ATII = can be used as an antidote

greater effect with UFH than LMWH

monitor partial thromboplastin time if using UFH