Lecture 8 Anti-coagulants Flashcards
Extrinsic pathway:
Factor(s) =
Other important molecule =
Lab test that measures it =
7;
thomboplastin aka tissue factor;
PT
“PT outside at 7”
Intrinsic pathway:
Factor(s) =
Lab test =
12, 11, 9, 8;
aPTT
common pathway:
Factors =
what does thrombin do
10, 5;
cleaves fibrinogen to fibrin
“10 / 5 = 2”
what 2 things are required to cross link/polymerize the fibrin molecules?
factor 13 (activated by thrombin)and calcium
all clotting factors except for VWF are produced in the _____.
liver
the ___ pathway is triggered when collagen is exposed on the wall of the blood vessel
intrinsic
_____ alters thrombin so it can activate protein C and S to inactivate what factors?
thrombomodulin;
5, 8
“CS58”
Antithrombin 3 (AT3) inhibits what factors? what are the important ones tho
thrombin (2), 7, 9, 10, 11, 12;
Xa and thrombin
Warfarin:
mechanism of action
inhibits vitamin K epoxide reductase (VKOR)
vitamin K is essential for ____ of the ____ in factors _____
gamma carboxylation, glu;
10, 9, 7, 2, C, S;
“1972 CS”
what lab measures warfarin action? what pathway?
PT, extrinsic
“the EX-PresidenT went to WAR”
how long does it take for warfarin to act?
3-5 days for full effect
long half life
What metabolizes warfarin? where does this occur
CYP2C9, in the liver
how to reverse warfarin overdose:
stop warfarin, then administer ____ and _____
Vitamin K, fresh frozen plasma
can you use warfarin during pregnancy?
no
drugs that effect warfarin:
pharmacokinetic interactions are related to ____.
pharmacodynamic interactions are related to ____
enzyme induction or inhibition;
interaction with clotting processes
Heparin:
binds the ____ charged region of ____. this _____ the reaction rate
positively, AT3; increases
heparin-AT3 complex mainly inhibits what 2 factors?
2 (thrombin) and 10
How long does it take for heparin to act?
immediate ie given via IV
short half life
what lab measures heparin action? what pathway?
aPTT, intrinsic
most common side effect of heparin and warfarin
increased bleeding
how do you reverse the action of heparin?
protamine sulfate (positively charged molecule binds heparin)
what is HIT? which form is worse?
heparin induced thrombocytopenia;
type 2
mechanism of HIT: heparin complexes with _____. this causes development of ____. this causes platelets to ____ and _____
platelet factor 4; IgG antibodies;
lyse, release activating granules –> hypercoaguable state
what other side effect does heparin have?
osteoporosis
is heparin positively or negatively charged? protein or polysacharride?
negatively charged, polysacharride
2 LWMH’s mentioned in FA
dalteparin, enoxaparin;
also danaparoid, tinzaparin
LMWH’s preferentially inhibit _____. what lab measures this?
factor Xa;
no lab does
LMWHs and fondaparinaux have a ____ half life than heparin. More or less risk of side effects? effect of protamine sulfate?
longer, less risk;
doesn’t really help
_____ is a synthetic indirect inhibitor of factor Xa
fondaparinaux
mechanism of action of rivaroxabn and apixaban:
directly inhibit factor Xa
factor Xa inhibitors are used for treatment and prophylaxis of ___, ___, and stroke prophylaxis in patients with _____
DVT, PE, Afib
what factor Xa inhibitor was recently approved.
how is it excreted?
edoxaban, renally
____ reverses factor Xa inhibition by acting as a decoy protein
andexanet
mechanism of action for argatroban, bivalirudin, dabigatran:
direct thrombin inhibitors
direct thrombin inhibitors are indicated for prevention of ____ and systemic embolism in patients with ___ AFib
stroke, non-valvular
what humanized monoclonal antibody inhibits a factor 10a inhibitor? what is the specific 10a inhibitor?
idarucizumab inhibits dabigatran
