Anticoagulant Drugs Flashcards
indications for anticoagulant drugs?
venous thrombosis atrial fibrillation (causes stasis of blood in left atrium which can clot and cause embolism so like venous thrombosis)
what di anticoagulant drugs target in general?
formation of fibrin clot
cadioembolic vs atheroembolic stroke?
cardioembolic = clot from AF commonly, treated with anticoagulants atheroembolic = due to atheroma in situ which ruptures, treat with anti platelets
naturally occurring anticoagulants?
anti thrombin
protein C and S
proteins C and S are dependant on what?
vitamin K
therefore affected by warfarin
what is used in acute venous thrombosis (DVT, PE, acute Afib etc)?
anticoagulants prevent clot forming/getting bigger and embolising but don’t dissolve the clot
heparin usually used which potentiates antithrombin and has an immediate effect
2 forms of heparin?
unfractionated
LMWH (most commonly used)
how does heparin work?
joins the anti-thrombin and thrombin complex and potentiates the effect of the antithrombin by keeping them bound together
also binds to activated clotting factor 10 and prevents its action
when is unfractionated heparin used?
can be used IV in few cases with complicated patients with history of bleeding
unfractioned heparin IV can be stopped and action stops very quickly
how is heparin therapy monitored?
APPT (thrombin feeds back to activate factors 8 and 9) - mainly needed for unfractioned
anti Xa assay can be used for LMWH but LMWH usually doesn’t need to be monitored
which does heparin prolong, APPT or PT?
both
APPT more sensitive however
potential complications in heparin therapy?
mainly bleeding
can have heparin induced thrombocytopaenia with thrombosis (HITT) due to immune reaction with antibodies to the heparin and platelets
can get osteoporosis with long term use (alters osteoclast activity)
how is heparin action reversed?
stop heparin (action reverses quickly in unfractioned but slower in LMWH) can give antidote to heparin if needed - protamine sulphate completely reverses antithrombin effect in unfractioned and partially in LMWH
what drugs might be used for a few months after a venous thrombosis (DVT etc) to reduce risk of a clot or a stroke etc?
warfarin (mainly)
warfarin mechanism?
inhibits vit K
where is vit K absorbed and what is needed?
upper intestine
needs bile salts to be absorbed
fat soluble vitamins?
A, D, E, K
which clotting factors does vit K carboxylate in the liver?
2, 7, 9, 10
what factors are dependant on vit K and will therefore become deficient without vit K?
protein C and S (decrease first)
factors 2, 7 9 and 10 (decrease a few days later)
why must heparin be given with warfarin?
warfarin initially makes you more pro-thrombotic due to decrease in protein C and S
action of vit K?
carboxylates glutamic acid residues in factors 2, 7, 9 and 10 as well as protein C and S
adds 1 of the 2 COOH groups essential for the clotting factor to bind through calcium to phospholipid
why is the second COOH needed in clotting factors for them to work?
second COOH group strengthens the chemical bond between clotting factor and platelet to form fibrin clot
problem with warfarin?
narrow therapeutic window due to metabolism
metabolism of warfarin?
in the liver
when is warfarin initiated rapidly?
acute thrombosis
done in hospital with heparin
when is warfarin initiated slowly?
AF liver failure malnourished elderly done in the community doesn't always needs heparin??
when should warfarin be taken?
same time every day
how is warfarin monitored?
INR
aim for 2 (2-3 can generally be accepted)
major adverse effects of warfarin?
haemorrhage
what might influence bleeding risk in warfarin?
intensity of anticoagulation
concomitant clinical disorders
concomitant use of other medications
quality of management
complications of mild bleeding?
skin bruising
epistaxis
haematuria
complications of severe bleeding?
GI bleeds
intracerebral bleeds
significant anaemia
how is warfarin action reversed?
omit a warfarin dose or two or reduce dose (If INR is a bit high and some bruising but nothing serious) > give oral vit K (if INR consistently high but no life-threatening bleeding) > give clotting factors (high INR and serious bleeding) > clinical and lab assessment of response
how long does vit K take to work vs clotting factors?
vit K = 6 hrs
clotting factors = immediate
other new anticoagulants?
oral direct thrombin inhibitors
oral Xa inhibitors
what clotting factors are affected by warfarin
prothrombin
VII
IX
X
what do the new anticoagulants target?
thrombin (e.g dabigatran) or Xa (e.g endoxaban, rivaroxaban, apixaban)
(Xa inhibitors preferred)
additional effect of warfarin that new anticoagulants don’t have?
also good for arterial thrombosis
