Haemostasis, thrombosis and platelet function

Question 1

Which three drug groups decrease clotting?

Answer 1

• Anticoagulants
• Antiplatelet
• Thrombolytics

Question 2

What is thrombosis?

Answer 2

unwanted haemostatic plug in a blood vessel or the heart

Question 3

What causes deep vein thrombosis?

Answer 3

poor blood flow

sitting for long periods of time

Question 4

What are the symptoms of deep vein thrombosis?

Answer 4

Swelling and heat in leg

Very painful

Question 5

What can result from a failure to treat deep vein thrombosis?

Answer 5

Loss of a leg

Question 6

Which two things can increase clotting?

Answer 6

• Replacement factors (VIII & IX)
• Plasminogen ihibitors

Question 7

Which enzyme does waraffin inhibit?

Answer 7

Vitamin K reductase

(stops carboxylation of glutamic acid residues = cannot bind platelet = no proteolysis = no cascade and no clotting)

Question 8

Which 3 drugs increase the action of waraffin and how?

Answer 8

• Aspirin = displace it from plasma proteins
• Sulphonamides = interferes with liver function
• NSAIDs = interferes with platelet function

Question 9

Which two patient factors increase the action of waraffin?

Answer 9

• Liver disease (decreases factor production and clearance)
• Reduced vitamin K availiability

Question 10

What is the average rate of onset for warrafin use?

Answer 10

12-16 hours

Question 11

How long do the effects of warrafin last once you stop taking it?

Answer 11

4-5 days

Question 12

How do we measure the action of warrafin in a patient?

Answer 12

Prothrombin time

(the time a sample takes to clot following addition of a standardised amount of Ca = ratio = compared to healthy subjects)

2-2.5 = prophylaxis of deep vein thrombosis

2. 5 = treatment of deep vein thrombosis/ pulmonary embolism
3. 5 = recurremt deep vein thrombosis/pulmonary embolism

Question 13

After starting a patient on warrafin at which intervals do we measure the action of warrafin?

Answer 13

Initially daily

Then at longer intervals

Then every 12 weeks

Question 14

Which two drugs decrease the action of warrafin and how?

Answer 14

• Barbituates = induce metabolising enzymes
• Colestipol (athlerosclerosis) = decreases absorption

Question 15

Which two patient factors decreases the action of warrafin?

Answer 15

• Increased vitamin K = promoted clotting factor synthesis
• Vomitting

Question 16

What are the side effects of Warrafin (2)?

Answer 16

• Haemorrhage in bowel or brain (stop administration & give vitamin K & replacement factors)
• Teratogenic (damages foetus)

Question 17

Name two injectable anticoagulants:

Answer 17

Heparin

Low molecular weight heparin

Question 18

Which two factors does heparin hit?

Answer 18

Factor IIa

Factor Xa

= activates antithrombin III

n.b. Heparin also binds to factor IIa but LMW heparin is too short = only hits factor Xa!!

Question 19

What is the main clinical use for heparin?

Answer 19

Clearing blocked IV catheters

Question 20

What inhibits heparin?

Answer 20

Factor IV (LMW heparin not inhibited)

Question 21

Can factor Xa bind to factors already bound to fibrin?

Answer 21

No

Question 22

What causes heparin to be badly absorbed in the gut?

Answer 22

Its large size and charge

Question 23

In which 2 ways can heparin be administered?

Answer 23

IV

Subcutaneous (LMW heparin only)

Question 24

Why is there an initial rapid removal of heparin?

Answer 24

Binds to plasma proteins (heparin only), endothelial cells and macrophages

Question 25

How is heparin excreted?

Answer 25

Slowly through renal excretion

Question 26

What are the side effects of heparin (5)?

Answer 26

* haemorrhage (counter with heparin antagonist e.g. protamine sulphate) * Thrombosis (rare -\> when antibodies against heparin cause endothelial damage) * Osteoporosis * Hypersensitivity * Hypoaldosteronism

Question 27

Name 4 examples of heparin:

Answer 27

heparin calciparine minihep monoparin

Question 28

Name 3 types of LMW heparin:

Answer 28

Certoparin Dalteparin Enoxaparin

Question 29

Name 3 antithrombin independant anticoagulants:

Answer 29

* Hirudin (binds thrombin active site -\> leeches) * Hirugen * Bivalirudin

Question 30

Which patients may antithrombin III independant anticoagulants be useful for?

Answer 30

Those who produce heparin antibodies

Question 31

What are the possible uses for antithrombin III independent anticoagulants?

Answer 31

Percutaneous coronary intervention (angioplasty) = rapid on/off effects = get patient out of hospital as quickly as possible

Question 32

What are the 3 main uses of anticoagulants?

Answer 32

* prevention of deep vein thrombosis (perioperatively since wound increases the liklihood of clot formation) * treatment of deep vein thrombosis * prevention of thrombosis on prosthetic heart valves

Question 33

Which enzyme does Aspirin irreversibly activate in platelets?

Answer 33

Cyclo-oxygenase

Question 34

How long does it take platelets to replace COX?

Answer 34

7-10 days

Question 35

Why is it that platelet cells cannot replace COX immediately but endothelial cells can?

Answer 35

Platelets do not have a nucleus!!

Question 36

When are antiplatelet drugs used?

Answer 36

In acute MI (myocardial infarction) in combination with fibrolytic drugs

Question 37

Tell me the following about Triclopine: Is it reversible or irreversible? What is its onset like? Which other drug does it have a similar efficacy to in reducing stroke?

Answer 37

Irreversible Slow (3-7 days) Aspirin

Question 38

What are the 3 main side effects of triclopidine?

Answer 38

Rash Diarrhoea neutropenia (loss of wbc)

Question 39

Tell me the following about clopidogrel: Is it reversible or irreversible? How is it administered?

Answer 39

Irreversible Oral prodrug

Question 40

Which group of individuals does clopidogrel not work in?

Answer 40

Those with a cytochrome p450 mutation

Question 41

When is clopidogrel given?

Answer 41

Given after heart surgery & after an MI

Question 42

Tell me the following about prasugrel: Is it reversible or irreversible? What is its onset like? What is its metabolism like?

Answer 42

Irreversible Faster onset (hours) More easily metabolised to its active metabolite

Question 43

Tell me the following about Ticagrelor: Is it reversible or irreversible? Which other two antiplatelet drugs does it have a similar efficacy to?

Answer 43

Reversible = stays in body for a couple of days only = can release patients faster! Clopidogrel & prasugrel

Question 44

Why can abciximab only be used once?

Answer 44

It is an antibody fragement directed against the receptor, repeated use = provokes immune response

Question 45

After use of abciximab how quickly does platelet function recover?

Answer 45

in days

Question 46

When is abciximab used?

Answer 46

IV in high risk coronary angioplasty patient on herparin & aspirin

Question 47

What is tirofiban/eptifibatide?

Answer 47

A cyclic peptide that resembles the IIb/IIIc ligands

Question 48

How is tirofiban/eptifibatide administered?

Answer 48

IV n.b. long term oral administration may be harmful

Question 49

How quickly is platelet function regained following use of tirofiban/eptifibatide?

Answer 49

hours

Question 50

Why are the prostaglandin agonists (epoprostenol) given intravenously?

Answer 50

It is chemicallly unstable

Question 51

When is Epoprostenol and other prostaglandin agonists used?

Answer 51

In patients undergoing haemodialysis (cannot use heparin)

Question 52

What is the effect of using the phosphodiesterase inhibitor dipyrimidole?

Answer 52

it increases platelet cAMP levels

Question 53

What are the 5 clinical uses of antiplatelet drugs?

Answer 53

* Following acute MI * Those at risk of MI * Following coronary bypass/angioplasty * Unstable coronary syndromes * following a cerebral stroke

Question 54

Name 3 plasminogen activators:

Answer 54

* Streptokinase * Recombinant tPA * Urokinase

Question 55

What do plasminogen activators do?

Answer 55

they produce plasmin = degradation of clot

Question 56

After administering streptokinase what must be done to block the function?

Answer 56

Give antistreptococcal after 4 days

Question 57

How long must you wait before reuse after giving a streptokinase?

Answer 57

1 year

Question 58

Which is the most commonly used plasminogen activator?

Answer 58

recombinant tPA

Question 59

What are the 3 types of recombinant tPA:

Answer 59

Anteplase/duteplase (short half life = IV infusion) Reteplase (longer half life = IV bolus)

Question 60

At which sites are recombinant tPA more active?

Answer 60

At fibrin bound plasminogen (clot specific!)

Question 61

What are the contraindications of Fibrolytic agents (7)?

Answer 61

* Active/recent internal bleeding * Recent cerebrovascular incident * Invasive procedures (where haemostasis is important) * Pregnancy (can cause loss of child) * If had cardipulmonary rescissitatopm for hours before * Trauma * Bacterial endocarditis

Question 62

What are the side effects of fibrolytic agents (3)?

Answer 62

* GI haemorrhage * Allergic reaction (/fever) * Hypotension (burst of plasmin by streptokinase)

Question 63

What are the clinical uses of fibrolytic agents (4)?

Answer 63

* Acute MI * Acute thrombotic stroke * Clear thrombosed shunts/cannulae * Acute arterial thromboembolism

Question 64

What are anti-thrombolytic drugs used for?

Answer 64

To stabilise a clot

Question 65

Name two antithrombolytic drugs:

Answer 65

* Tranexamic acid * Aprotinin

Question 66

How does tranexamic acid work?

Answer 66

Inhibits activation of plasminogen (stabilises clot)

Question 67

How is tranexamic acid administered?

Answer 67

Oral/IV

Question 68

When is tranexamic acid used clinically?

Answer 68

when increased risk of bleeding (e.g. dental extraction, prostoectomy etc)

Question 69

What are the side effects of tranexamic acid?

Answer 69

Nausea & vomitting

Question 70

How does aprotinin work?

Answer 70

Proteolytic inhibitor of plasmin/kallikrein

Question 71

How is aprotinin administered?

Answer 71

slow IV

Question 72

When is aprotinin used clinically?

Answer 72

patients of high risk of blood loss (e.g. open heart surgery)