14. Anti-Platelets and Anticoagulants Flashcards
What is the difference between white clots and red clots?
White clots are rich in platelets, red clots are rich in clotting factors.
What are the three components of Virchow’s triad?
Hypercoagulability, endothelial damage, and stasis.
What can cause hypercoagulability?
Genetics - protein C/S deficient, factor V leiden. Acquired - SLE, OCP, smoking, malignancy.
What can cause endothelial damage?
Atheroma in MI/CVA, hypertension, toxins - cigarettes/homocysteine.
What can cause stasis?
Immobility - ill health, post-op, economy class; cardiac abnormality - AF, CCF, mitral valve disease, post MI.
Name an anticoagulant.
Warfarin.
What is the mechanism of action of Warfarin?
Inhibits production of vitamin K dependent clotting factors so less II, VII, IX, and X (extrinsic pathway). This is by competitive inhibition.
What is the onset time for Warfarin to have an effect?
Days - slow half life of clotting factors.
Why can warfarin be given orally?
Good GI absorption.
Why is heparin needed alongside warfarin initially?
Because warfarin has a slow onset of action.
Why must warfarin be stopped 3 days before surgery?
It has a slow offset due to long half life, stopping early allow time to synthesise new clotting factors.
How is warfarin metabolised?
Hepatic metabolism using cytochrome p450 system.
Why must warfarin be avoided during pregnancy?
T1 - teratogenic, T3 - brain haemorrhage.
How can warfarin be monitored?
Extrinsic pathway factors, prothrombin time, INR (international normalised ratio).
What is the prothrombin time?
Citrated plasma clotting time after adding calcium and thromboplastins.
What is the purpose of having an international normalised ratio (INR)?
Allows a standard value corrected for different lab thromboplastin reagents.
What are the drug interactions to be wary of with warfarin?
Effects on anticoagulation - most increase anticoagulant effect, some do decrease it.
Name a drug that inhibits hepatic metabolism and the effect it has on warfarin.
Amiodarone, quinolone, metronidazole, cimetidine, alcohol. All potentiate warfarin.
Name a drug that inhibits platelet function and the effect it has on warfarin.
Aspirin, potentiates effect.
Name a drug that reduces vitamin K from gut bacteria and the effect it has on warfarin.
Cephalosporin antibiotics, potentiates effect.
How do NSAIDs impact action of warfarin?
They displace binding to albumin so potentiates warfarin effect slightly.
Name a drug that inhibits warfarin.
Antiepileptics, rifampicin, St Johns Wort.
How do inhibitors of warfarin work?
Induce hepatice enzymes so increase metabolism.
What are the indications of use of warfarin?
DVT, PE, atrial fibrillation, mechanical prosthetic valves, recurrent thromboses on warfarin, thrombosis associated with inherited thrombophilia conditions.
How long should warfarin be use in the cases of DVT, PE, and AF?
DVT 3-6 months, PE 6 months, AF until risk > benefit.
What is the goal INR for warfarin therapy in DVT, PE and AF?
2.0-3.0.
What is the goal INR for warfarin use in mechanical prosthetic valves, recurrent thromboses, or thrombophilia?
2.5-4.5.
What are the ADRs of warfarin?
Bleeding/bruising intracranially, epistaxis, injection, or in GI tract. Also teratogenic.
What is a safety issue with a high INR?
Risk of brain haemorrhage if over 3.5.
How can warfarin therapy be reversed?
Parenteral vitamin K (slow effect), or fresh frozen plasma (fast effect).
What should be considered when prescribing warfarin?
Indications, PMH, medication (DDIs), age, mobility, falls risk score, blood tests, loading dose and heparin cover, and when to start.
What should be discussed with the patient before starting warfarin therapy?
Side effects, if female talk about teratogenicity, interactions with other medications and OTC and alcohol/cranberry juice/grapefruit juice, need to INR monitoring, and give them an anticoagulant card.
What is the mechanism of action for heparins?
Activate anti-thrombin III.
What are the two types of heparin molecule?
Unfractionated heperan with variety of molecular weights, low molecular weight heparins.
What is the route of administration for unfractionated heparin and LMWH?
UH - IV, LMWH - SC.
What is the mechanism of action of unfractionated heparin?
Binds to anti-thrombin III to increase activity, this inactivates thrombin and factor Xa.
Which types of heparin can inhibit thrombin and inhibit factor Xa?
Thrombin - only unfractionated heparin is large enough. Xa - both can bind.
How does LMWH differ from UH in terms of size, bioavailability, half life, and dose response?
LMWH is smaller (<18 saccharide units), higher bioavailability with more uniform absorption, longer half life, more predictable dose response.
What is the mechanism of action of LMWH?
Affect factor Xa specificially.
What is the route of clearance of LMWH?
Kidneys.
Why must heparin be given parenterally?
Poor GI absorption.
How fast is onset/offset of heparin?
Rapid.
How is UFH monitored?
APTT test.
What are the indications for use of heparin?
Peri-operative, immobility, DVT/PE and AF, acute coronary syndromes, pregnancy.
What are the ADRs of heparin?
Bruising/bleeding sites (intracranial, injection sites, GI, epistaxis), thrombocytopenia (HIT), osteoporosis (long term use).
What is thrombocytopenia?
An autoimmune condition causing bleed or serious thromboses, with depleted platelets.
How can heparin therapy be reversed?
Protamine sulphate - dissociates heparin from anti-thrombin III.
Name an anti-platelet drug and a brief mechanism of action.
Aspirin (COX-1 inhibition), dipyridamole (phosphodiesterase inhibitors), clopidogrel (ADP antagonists), glycoprotein IIb/IIIa inhibitors.
What is the process of thrombotic occlusion by platelets?
Plaque fissure/rupture, platelet aggregation, platelet activation, platelet aggregation, thrombotic occlusion.
When is clopidogrel used?
With aspiring and cardiac indications.
What is dipyridamole used for?
Secondary prevention of stroke.
What are the uses of glycoprotein IIb/IIIa receptor antagonists?
High risk ACS, post PCI.
