Anticoagulant drugs

Question 1

Give indications for anticoagulant drugs?

Answer 1

Venous thrombosis
Atrial fibrillation
Arterial thrombosis
TIA

Question 2

What do anticoagulants target in venous thrombosis?

-which drug is given in AF? why?

Answer 2

• secondary haemostasis
• Warfarin, stasis within L atrium predisposes to a fibrin clot, high risk of this breaking off into circulation and so need warfarin to prevent

Question 3

Heparin

• mode of action?
• speed of effect?
• route of administration?
• forms?
• monitering?
• SE?
• reversal?
• why is it effective for use prior to surgery?

Answer 3

• Potentiates antithrombin, antithrombin works more effectively and this inactivates thrombin and factor 10
• immediate
• parenteral (IV/SC)

-unfractionated (more of n effect on thrombin)
LMWH (more of an effect on Factor X, predictable and fewer SE)

-unfractionated- APTT
LMWH- not needed normally, Anti-Xa assay

-Bleeding mainly
heparin induced thrombocytopenia (with thrombosis)HITT- check plts after 5-10 days
Osteoporosis long term (affects osteoclasts)

-Stop heparin (short half life)
if severe- protamine sulphate (complete reversal of unfractionated and partial reversal of LMWH)

-short half life

Question 4

Coumarin anticoagulants

• name 4 drugs in this category
• what is their mechanism of action

Answer 4

Warfarin, Phenindione, acenocoumarin, phenprocoumon

-Inhibition of Vit K

Question 5

Vitamin K

• type of vitamin?
• where is it absorbed & how?
• what is it’s function?
• Where is Vit K synthesised?

Answer 5

• fat soluble
• upper intestine, needs bile salts for absorption
• final carboxylation of glutamic acid residues in clotting factors II, VII, IX, X, protein S and C are also Vit K dependent
• the liver

Question 6

Warfarin

• mechanism of action?
• indications?
• monitering?
• maintenance?
• SE & factors affecting severity?
• reversal (depending on severity)?

Answer 6

• blocks the ability of Vit K to carboxylate Vit K dependent clotting factors in the liver so reducing coagulant activity
• for slow initiation, e.g. AF in community

-narrow therapeutic window, so need to have blood tests eery 6 wks after they have stabilised
checked using the INR- should be 2-3 when on Warfarin

-Take at the same time every day

-haemorrhage, 
Mild 
(skin bruising, epistaxis, haematuria)
Severe
(GI, Intracerebral, Significant drop in Hb)
factors that affect the risk of this are:
intensity of anticoagulation
Concomitant use of other medications 
Drug interactions
Quality of management 

-Omit dose (2-3 days)
Administer oral Vit K 1-2mg (6 hrs)
Administer clotting factors (FFP or Factor conc- immediate)

Question 7

What is the INR?

-describe the equation used to calculate INR

Answer 7

INR= international normalised ratio
It is a mathematical “correction” (of the PT ratio) for differences in the sensitivity of thromboplastin reagents and allows for comparison of results between labs and standardises reporting of the prothrombin time

-(Patients PT in seconds / Mean normal PT in seconds) x ISI

ISI- international sensitivity index

Question 8

Give the 2 types of new anticoagulants?

• advantages?
• disadvantages?
• indications?

Answer 8

Thrombin inhibitors e.g. dabigatran (oral)
Xa inhibitors e.g. Rivaroxaban, Apixaban

-oral
no monitoring required
Less drug interactions

-Currently no specific antidote for reversal
?kidney injury

-prophylaxi prior to surgery
stroke and AF [revention in some patients
DVT/PE