Haemostasis - Anti-Coagulant Therapy Flashcards
indications for anticoagulation
venous thrombosis
atrial fibrillation
mechanical prosthetic heart valve
what is heparin? what cells produce it?
GAG, produced by mast cells, anticoagulant
actions of unfractionated heparin
enhancement of antithrombin [Inactivation of thrombin (Hep binds AT + Thrombin)
Inactivation of FXa (Hep binds AT only)
(Inactivation of FIXa, FXIa, FXIIa)]
actions of low molecular weight heparin
Contain pentasaccharide sequence for binding AT
Predictable dose response in most cases so does not require monitoring (cf UFH)
how is unfractionated heparin administered?
intravenous
how is low molecular weight heparin administered?
subcutaenous
describe a graph showing the relationship between dose of UFH and LMWH to APPT
both curves
UFH steeper curve
what are coumarins?
vitamin K antagonists
list an example of a coumarin
warfarin
mechanism of action of warfarin
inhibits vitamin K epoxide reductase > reduces production of functional coagulation factors
does warfarin administration require monitoring?
yes, due to narrow therapeutic index
many dietary, physiological and drug interactions
is the action of warfarin reversible?
yes
how to reverse warfarin action slowly?
vitamin K administration
how to reverse warfarin action rapidly?
by infusion of coagulation factors:
Prothrombin Complex Concentrate- contains Factors II, VII, IX and X or
Fresh Frozen Plasma
side effects of warfarin
bleeding
skin necrosis
purple toe syndrome
embryopathy - chondrodysplasia punctata
skin necrosis when taking warfarin
Severe Protein C deficiency
2-3 days after starting Warfarin
Thrombosis predominantly in adipose tissues
purple toe syndrome when taking warfarin
Disrupted atheromatous plaques bleed
Cholesterol emboli lodge in extremities
chondrodysplasia punctata when taking warfarin
Early fusion of epiphyses
Warfarin teratogenic in 1st trimester
what is INR?
international normalised ratio
used to monitor patients on warfarin
how to calculate INR?
patient prothrombin time to normal prothrombin time
target INR is usually?
2-3
describe the relationship between bleeding risk and INR on a graph
steep curve
as INR increases, so does bleeding risk
resistance to warfarin
lack of patient complicance
diet, increased vitamin K intake
increased metabolism Cyt P450 (CYP2C9)
reduced binding (VKORC1)
which DOACs act to inhibit factor Xa?
rivaroxaban
apixaban
edoxaban
which DOACs act to inhibit factor IIa?
dabigatran
comparison between warfarin and DOACs
W: slow onset, variable dosing, many interactions and food effect, requires monitoring, reversible with vit K, PCC
DOACs: rapid onset, fixed dosing, no food effect, few interactions, no monitoring, some renal dependence, antidote for dabigatran
choice of anticoagulant for initial treatment of venous thrombosis
DOAC or LMWH for first few days followed by DOAC or warfarin
choice of anticoagulant for long term treatment of venous thrombosis
DOAC or warfarin
choice of anticoagulant for treatment atrial fibrillation
DOAC or warfarin
choice of anticoagulant for mechanical prosthetic heart valve
Warfarin (DOACs not effective and should be avoided)
choice of anticoagulant for prophylactic treatment following surgery
LMWH or DOAC
choice of anticoagulant for prophylactic treatment during pregnancy
LMWH (DOACs not safe in pregnancy)
