Haemostasis, thrombosis and platelet function Flashcards
Which three drug groups decrease clotting?
- Anticoagulants
- Antiplatelet
- Thrombolytics
What is thrombosis?
unwanted haemostatic plug in a blood vessel or the heart
What causes deep vein thrombosis?
poor blood flow
sitting for long periods of time
What are the symptoms of deep vein thrombosis?
Swelling and heat in leg
Very painful
What can result from a failure to treat deep vein thrombosis?
Loss of a leg
Which two things can increase clotting?
- Replacement factors (VIII & IX)
- Plasminogen ihibitors
Which enzyme does waraffin inhibit?
Vitamin K reductase
(stops carboxylation of glutamic acid residues = cannot bind platelet = no proteolysis = no cascade and no clotting)
Which 3 drugs increase the action of waraffin and how?
- Aspirin = displace it from plasma proteins
- Sulphonamides = interferes with liver function
- NSAIDs = interferes with platelet function
Which two patient factors increase the action of waraffin?
- Liver disease (decreases factor production and clearance)
- Reduced vitamin K availiability
What is the average rate of onset for warrafin use?
12-16 hours
How long do the effects of warrafin last once you stop taking it?
4-5 days
How do we measure the action of warrafin in a patient?
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
- 5 = treatment of deep vein thrombosis/ pulmonary embolism
- 5 = recurremt deep vein thrombosis/pulmonary embolism
After starting a patient on warrafin at which intervals do we measure the action of warrafin?
Initially daily
Then at longer intervals
Then every 12 weeks
Which two drugs decrease the action of warrafin and how?
- Barbituates = induce metabolising enzymes
- Colestipol (athlerosclerosis) = decreases absorption
Which two patient factors decreases the action of warrafin?
- Increased vitamin K = promoted clotting factor synthesis
- Vomitting
What are the side effects of Warrafin (2)?
- Haemorrhage in bowel or brain (stop administration & give vitamin K & replacement factors)
- Teratogenic (damages foetus)
Name two injectable anticoagulants:
Heparin
Low molecular weight heparin
Which two factors does heparin hit?
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!!
What is the main clinical use for heparin?
Clearing blocked IV catheters
What inhibits heparin?
Factor IV (LMW heparin not inhibited)
Can factor Xa bind to factors already bound to fibrin?
No
What causes heparin to be badly absorbed in the gut?
Its large size and charge
In which 2 ways can heparin be administered?
IV
Subcutaneous (LMW heparin only)
Why is there an initial rapid removal of heparin?
Binds to plasma proteins (heparin only), endothelial cells and macrophages
How is heparin excreted?
Slowly through renal excretion
What are the side effects of heparin (5)?
- haemorrhage (counter with heparin antagonist e.g. protamine sulphate)
- Thrombosis (rare -> when antibodies against heparin cause endothelial damage)
- Osteoporosis
- Hypersensitivity
- Hypoaldosteronism
Name 4 examples of heparin:
heparin
calciparine
minihep
monoparin
Name 3 types of LMW heparin:
Certoparin
Dalteparin
Enoxaparin
Name 3 antithrombin independant anticoagulants:
- Hirudin (binds thrombin active site -> leeches)
- Hirugen
- Bivalirudin
Which patients may antithrombin III independant anticoagulants be useful for?
Those who produce heparin antibodies
What are the possible uses for antithrombin III independent anticoagulants?
Percutaneous coronary intervention (angioplasty) = rapid on/off effects = get patient out of hospital as quickly as possible
What are the 3 main uses of anticoagulants?
- 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
Which enzyme does Aspirin irreversibly activate in platelets?
Cyclo-oxygenase
How long does it take platelets to replace COX?
7-10 days
Why is it that platelet cells cannot replace COX immediately but endothelial cells can?
Platelets do not have a nucleus!!
When are antiplatelet drugs used?
In acute MI (myocardial infarction) in combination with fibrolytic drugs
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?
Irreversible
Slow (3-7 days)
Aspirin
What are the 3 main side effects of triclopidine?
Rash
Diarrhoea
neutropenia (loss of wbc)
Tell me the following about clopidogrel:
Is it reversible or irreversible?
How is it administered?
Irreversible
Oral prodrug
Which group of individuals does clopidogrel not work in?
Those with a cytochrome p450 mutation
When is clopidogrel given?
Given after heart surgery & after an MI
Tell me the following about prasugrel:
Is it reversible or irreversible?
What is its onset like?
What is its metabolism like?
Irreversible
Faster onset (hours)
More easily metabolised to its active metabolite
Tell me the following about Ticagrelor:
Is it reversible or irreversible?
Which other two antiplatelet drugs does it have a similar efficacy to?
Reversible = stays in body for a couple of days only = can release patients faster!
Clopidogrel & prasugrel
Why can abciximab only be used once?
It is an antibody fragement directed against the receptor, repeated use = provokes immune response
After use of abciximab how quickly does platelet function recover?
in days
When is abciximab used?
IV
in high risk coronary angioplasty patient on herparin & aspirin
What is tirofiban/eptifibatide?
A cyclic peptide that resembles the IIb/IIIc ligands
How is tirofiban/eptifibatide administered?
IV
n.b. long term oral administration may be harmful
How quickly is platelet function regained following use of tirofiban/eptifibatide?
hours
Why are the prostaglandin agonists (epoprostenol) given intravenously?
It is chemicallly unstable
When is Epoprostenol and other prostaglandin agonists used?
In patients undergoing haemodialysis (cannot use heparin)
What is the effect of using the phosphodiesterase inhibitor dipyrimidole?
it increases platelet cAMP levels
What are the 5 clinical uses of antiplatelet drugs?
- Following acute MI
- Those at risk of MI
- Following coronary bypass/angioplasty
- Unstable coronary syndromes
- following a cerebral stroke
Name 3 plasminogen activators:
- Streptokinase
- Recombinant tPA
- Urokinase
What do plasminogen activators do?
they produce plasmin = degradation of clot
After administering streptokinase what must be done to block the function?
Give antistreptococcal after 4 days
How long must you wait before reuse after giving a streptokinase?
1 year
Which is the most commonly used plasminogen activator?
recombinant tPA
What are the 3 types of recombinant tPA:
Anteplase/duteplase (short half life = IV infusion)
Reteplase (longer half life = IV bolus)
At which sites are recombinant tPA more active?
At fibrin bound plasminogen (clot specific!)
What are the contraindications of Fibrolytic agents (7)?
- 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
What are the side effects of fibrolytic agents (3)?
- GI haemorrhage
- Allergic reaction (/fever)
- Hypotension (burst of plasmin by streptokinase)
What are the clinical uses of fibrolytic agents (4)?
- Acute MI
- Acute thrombotic stroke
- Clear thrombosed shunts/cannulae
- Acute arterial thromboembolism
What are anti-thrombolytic drugs used for?
To stabilise a clot
Name two antithrombolytic drugs:
- Tranexamic acid
- Aprotinin
How does tranexamic acid work?
Inhibits activation of plasminogen (stabilises clot)
How is tranexamic acid administered?
Oral/IV
When is tranexamic acid used clinically?
when increased risk of bleeding (e.g. dental extraction, prostoectomy etc)
What are the side effects of tranexamic acid?
Nausea & vomitting
How does aprotinin work?
Proteolytic inhibitor of plasmin/kallikrein
How is aprotinin administered?
slow IV
When is aprotinin used clinically?
patients of high risk of blood loss (e.g. open heart surgery)
