Anticoagulants

Question 1

Are anticoagulants used for venous or arterial thrombi?

Answer 1

Venous - driven by coagulation cascade and fibrin

Arterial thrombi are platelet rich so use antiplatelets

Question 2

What is the function of AT111?

Answer 2

Endogenous inactivator of many clotting factors

Question 3

Mechanism of heparins

Answer 3

Enhance AT111 activity - inactivated clotting factors

Question 4

Differences between unfractionated and LMW heparin

Answer 4

UFH: fast onset of action but irregular polysaccharides mean mixed elimination, so half life is unpredictable.
Give IV bonus
Binds to AT111 which inhibits factor Xa

LMWH: uniform polysaccharides so more predictable half life. And does not bind to endothelial cells so predictable response.
Always subcut administration

Specific inhibition of Xa by enhancing AT111

Question 5

Example of LMWH

Answer 5

Dalteparin
Enoxaparin

Question 6

Heparin suitable for Muslims/vegans?

Answer 6

Fondaparinux

Synthetic

Question 7

Do you have to monitor patients on UFH or LMWH and how

Answer 7

UFH needs aPTT monitoring

Due to unpredictable metabolism

Question 8

Indications for heparins and fondaparinux

Answer 8

Prevention VTE - DVT and PE
Perioperative prophylaxis with LMWH
AF

Question 9

ADRS of heparins

Answer 9

Bruising and bleeding - GI, epistaxis, intracranial

HIT (thrombocytopenia)
Hyperkalaemia
Osteoporosis

Question 10

Contras and DDIs of heparins

Answer 10

Do not give in clotting disorders, GI ulcers, renal impairment (renal excretion of LMWH and fondaparinux)

DDis antithrombotic drugs, ACEi/ARBs, potassium sparing diuretics

Question 11

Antidote to heparin, and administration and action?

Answer 11

Protamine sulphate IV

Forms irreversible complex with heparin
Dissociates heparin from AT111

Much greater effect with UFH!!

Question 12

Warfarin mechanism

Answer 12

Competitive inhibitor of VKOR
Inhibits conversion of bit K to active, reduced form
Inhibits activation of bit K dependant clotting factors

Works on both intrinsic and extrinsic pathways

Question 13

Does warfarin work immediately?

Answer 13

No, delay in onset of action

As circulating active clotting factors are present for several days

Heparin cover required if anticoagulation needed immediately

Question 14

Indications for warfarin

Answer 14

VTE
PE
DVT
AF where DOAC not suitable

Question 15

Explain warfarin pharmacokinetics

Answer 15

Good GI (oral) absorption
Zero order kinetics - plasma conc. does not correlate directly with clinical effect

Racemic mixture of R and S - both metabolised differently

Teratogenic in 1st trimester

Question 16

Warfarin monitoring

Answer 16

Monitor INR

Restart when <5

Question 17

Target INR for DVT, PE and AF

Answer 17

2.5

Question 18

Warfarin ADRS and management

Answer 18

Bleeding - epistaxis and spontaneous retro peritoneal!!

Give vit K, stop warfarin.
Give prothrombin complex (antidote)

Question 19

Warfarin DDis

Answer 19

CYP 2C9 inhibitors - amiodarone, metronidazole, alcohol - increase plasma warfarin. Inhibit hepatic metabolism

NSAIDS - displace warfarin from plasma albumin. Increase INR = more anticoagulation (bleeding risk)

Barbiturates, phenytoin, rifampicin, St John’s wort - accelerate warfarin metabolism. Inducers

Question 20

DOAC examples

Answer 20

Apixaban - good side effect profile!
Edoxaban
Rivaroxaban

Xa=direct Xa acting

Question 21

DOAC mechanism

Answer 21

Inhibits free Xa and Xa bound to AT111

Question 22

Dabigatran mechanism

Answer 22

Direct 2a competitive inhibitor (clotting factor)

Both free and thrombus bound 2a

Question 23

DOAC ADRS

Answer 23

Bleeding
Skin reactions

Question 24

DOAC contras and DDIS

Answer 24

Avoid in pregnancy
Dabigatran contraindicated in low eGFR (renal metabolism)
Plasma concentration reduced by carbamazepine and phenytoin