3.5 Anticoagulant drugs Flashcards
what are the indications for anticoagulant drugs?
venous thrombosis
atrial fibrillation
How does heparin work?
heparin potentiates anti-thrombin III antithrombin III inhibits clotting factors -TF/VIIa -VIII/IXa -V/Xa -thrombin
it works by stabilizing the bond between ATIII and thrombin or factor Xa (LMWH) because of its negative charge. (AT III and clotting proteins are + charged)
why is it important that heparin inhibits thrombin in the coagulation cascade?
- thrombin cleaves fibrinogen to fibrin- final product
2. thrombin activates factors VIII/IXa which amplifies haemostasis (intrinsic pathway)
How does protein C and protein S work?
protein C and S are natural anticoagulants on platelets.
they are activated by thrombin bound to thrombomodulin on endothelial cells
protcein C and S inhibit V/Xa and VIII/IX clotting factors
How quickly does heparin work?
Heparin works immediately
potentiates antithrombin
IV or SC
unfractionated or LMWH
what are the targets of LMWH?
thrombin or factor Xa - to help it bind to antithrombin III
what is measured to monitor heparin?
activated partial thromboplastin time - APTT
for unfractionated heparin only
what is measured to monitor LMWH?
usually no monitoring
anti-Xa assay can be done
What is measured to monitor warfarin?
PT or INR
what clotting factors are measured by PT?
intrinsic or extrinsic pathway?
TF/VIIa
extrinsic pathway
what clotting factors are measured by aPTT?
VIII/Xa
intrinsic pathway for amplification
what are the complications of heparin use?
bleeding heparin induced thrombocytopaenia- HITT, monitor FBC in patients on heparin. mx: stop heparin, change drgs osteoporosis with long term use allergy rash
How do you reverse heparin?
stop heparin- half life in unfractioned is 30 min, LMWH is 12 hours
protamine sulphate- doesn’t reverse anti-Xa effect
- complete reversal for heparin
- incomplete reversal for LMWH
what is the half life of unfractioned heparin?
30 min
half life of LMWH?
12 hours
what are the coumarin anticoagulants?
warfarin
phenindione
acenocoumarin
phenprocoumon
mechanism of action of warfarin
inhibit vitamin K
vit K needed for final carboxylation of clotting factors II, VII, IX, X
(protein C and S- also need carboxylation to work, so clotting may be increased in initial use of warfarin)
where is vit K absorbed?
upper intestine
requires bile salts because fat soluble vitamin
How long should you cover a patient with heparin when they are starting warfarin?
5-7 days
unles very slow start is an option
synthesis of coagulation factors is reduced in warfarin therapy
true or false?
false
there is a synthesis of NON-FUNCTIONAL coagulation factors from the liver in antagonism of vitamin K
does warfarin act on intrinsic or extrinsic pathway?
the extrinsic pathway
because factors II, VII, IX, X are inhibited through non-functional production
and extrinsic pathway is TF/VIIa
also the final common pathway (V/Xa) is inhibited
how do you start warfarin therapy?
initiation- can be rapid or slow, with heparin cover
stabilization- may need dose adjustment
maintenance- take warfarin at same time every day, check levels if dose changed within a few days
what is the INR equation?
INR= patient’s PT in seconds / normal PT in seconds ) ^international sensitivity ratio
the goal is 2-3
what are the adverse effects of warfarin?
HAEMORRHAGE
- consider PMH- peptic ulcer disease?
- consider MH- antibiotics?
- consider diet- cranberry or grapefruit juice? dose may need to be decreased
- consider alcohol
skin bruising, epistaxis, haematuria
gastrointestinal bleeding
intracerebral bleeding- 1/200 per year get this, and 1/2 die before getting to hospital, even with normal INR
decreased Hb
