Anti-coagulants Flashcards
What activates the instrinsic pathway?
Exposed collagen
What activates the extrinsic pathway?
Tissue factor
Summarise the clotting cascade
- Extrinsic and intrinsic pathway activate factor X->Xa
- This activates prothrombin to thrombin
- This activates fibrinogen to fibrin and forms a clot
What electrolyte is important in the clotting cascade?
Calcium
How is unfractionated heparin given?
IV bolus/infusion
SC for prophylaxis as it gives a much lower bioavailiability
What is unfractionated heparin mechanism of action?
- Binds to ATIII and causes a conformational change, increasing activity of ATIII
How does unfractionated heparin inhibit thrombin?
It needs to bind simultaneously to ATIII and IIa
How does unfractionated heparin inhibit factor Xa
It only needs to bind to ATIII
Name two LMWH’s
Dalteparin, enoxaparin
How is LMWH given?
Subcutaneously
How does LMWH work?
It bind to ATIII and inhibits factor Xa only
How does fondaparinux work?
It is a synthetic polysaccharide which selectively inhibits Xa by binding to ATIII. Given subcutaneously, t1/2 is 18 hours.
Why does UFH need more monitoring?
How do you monitor it?
The dose response is non linear with variable bioavailability. It is monitored by looking at aPTT.
Which heparin do you use in renal impairment?
UFH
Which heparin do you use if you need fine control?
UFH
Which heparin has a longer half life?
LMWH
What are some ADR’s related to heparin?
- Bruising and bleeding - intracranial, GI, epistaxis
- Heparin induced thrombocytopenia - Antibodies to heparin platelet factor 4 complex. Platelets deplete but can lead to thrombosis as more platelets activated by damaged endothelium.
- Hyperkalaemia - Aldosterone inhibited
- Osteoporosis
What is protamine sulfate?
It forms an inactivate complex with heparin, given IV.
It dissociated heparin from ATIII and causes irreversible binding.
How does warfarin work?
Inhibits activation of vitamin K dependent clotting factors. Hepatic synthesis of 2, 7, 9 ,10
Does warfarin work straight away?
No - takes a while as circulated active clotting factors have be used up and takes several days.
What is the half life of warfarin?
36-48hrs
Can you give warfarin in pregnancy?
No. Avoid in 1st trimester (teratogenic) and 3rd trimester (haemorrhage).
What are some ADR’s of warfarin?
- Bleeding
2. Epistaxis and spontaneous retroperitoneal bleeding
What is a good antidote to warfarin?
Vitamin K
Prothrombin complex IV
Stop warfarin
What is bridging therapy?
Giving LMWH when initiating or temporarily stopping warfarin (surgery, sickness)
What are the warfarin DDI’s
- Any drug that interacts with enzyme inducers/inhibitors
Amidodarone, clopidogrel, high alcohol dose, quinolone, metronidazole,
- cephalosporins (they reduce gut bacteria that inhibit vit K)
- NSAID’s - Displace warfarin from plasma albumin. Decreased gut absorption of vit K. Increase INR.
- ‘CRAPS’ P450 inducers decrease INR.
How do you monitor a patient on warfarin?
INR
What is an ideal INR?
<1.1
What is a target INR in patients with DVT, PE, AF?
INR 2-3
What is a target INR in patients with recurrent DVT or PE?
3.0 - 3.5
Name 3 DOAC’s
Apixaban, edoxaban, rivaroxaban
How do DOAC’s work?
They inhibit free Xa and those bound to ATIII. Hepatic metabolism and slightly kidneys. Half life 10hrs.
How does dabigatran work
A direct competitive thrombin inhibitor, both circulating and thrombus bound IIa.
Do you need to monitor DOAC’s?
No
How are DOAC’s given?
Orally
What are some ADR’s of DOAC’s?
- Bleeding, caution in GI bleed groups
- Metabolism by many routes. Don’t use dabigatran in low creatinine clearance.
- Affects by CYP inhibitors/inducers. Plasma increased by macrolides.
- Lower intracranial bleed risk than warfarin.
Can you use DOAC’s in pregnancy?
No
Is there an antidote for DOAC’s?
Yes, andexanet.
When is warfarin used over a DOAC?
In renal failure, mechanical valves, if you need to measure compliance
