Anticoags Flashcards
coag factors are ___
enzymes
each step of the cascade amplifies the ___
initial signal
coag factors are made in the ___
liver
“Final pathway” results in:
conversion of prothrombin (II) to thrombin
which catalyzes the conversion of fibrinogen to fibrin
fibrin activates the ____
fibrinolytic system (plasmin, tissue plasminogen activator (tPA))
Homeostasis of the cascade is maintained by balance of
procoagulants (coag factors) endogenous anticoagulants (proteins C & S, antithrombin III)
proteins C and S are important for ___
warfarin dosing
antithrombin III is important for ___
heparin dosing
purpose of fibrinolytic system
degrades fibrin
fibrinolytic system results in:
fibrin split products (FSP) AKA fibrin degredation products (FDPs) Fibrin dimers (d-dimers)
increased fibrin degradation product or d dimer levels suggest presence of ___
thrombi
consequence of inappropriate thrombosis:
venous thrombi
arterial thrombi
venous thrombi:
DVT
Red thrombus AKA venous stasis thrombi
VTE (venous thromboembolism)
arterial thrombi are __ driven
platelet driven
complication of venous thrombi
pulmonary embolism
arterial thrombi
white thrombus
complication of arterial thrombi
strokes, myocardial infarction
thrombosis risk factors
surgery cancer immobility varicose veins pregnancy
potential complication of anticoagulant agents
BLEEDING
complications of anticoagulation agents are NOT an ___. it is an extension of their ___
allergy; MOA
heparin binds to ___
antithrombin III
heparin binding requires specific _____
pentasaccharide sequence
Heparin’s limitations
heparin activates platelets directly
Heparin can dinduce immune response in the form of HIT/HITTs
Heparin exhibits nonlinear dose response
Heparin increases affinity of thrombin for fibrin
unfractionated heparin is a :
heterogenous mix of sulfated glycosaminoglycans
only ___ of UFH molecules have the pentasaccharide
~1/3
UFH antithrombin complex is approx ______ x > anticoagulant than antithrombin alone
100-1000x
UFH is only effective on ____ fibrin
soluble (non clot-bound fibrin)
UFH prevents the ____ of the thrombus
growth/propagation
UFH allows the patient’s fibrinolytic system to ___
degrade the clot
UFH is measured by the ______
activated partial thromboplastin time aPTT)
DVT prophylaxis – subQ heparin
UFH
5,000 units SubQ q12h or q8h
Risk of HIT is that of ___ UFH
IV (increased risk)
Advantages of UFH
immediate anticoag measured by aptt effects reversed by protamine prevents propagation of a clot may be given subQ for prophylaxis usually done by Pharmacy Dosing Service
disadvantages of UFH
non-linear kinetics frequent lab tests required increased risk of bleeding potential for life-threatening immune-mediated thrombocytopenia "HIT) minimal effect on interior of the clot
___ is used to reverse UFH heparins
protamine sulfate
MOA of protamine sulfate
combines with strongly acidic heparin
2 types of HIT
HIT 1 (non-immune) 10% HIT II (immune) VERY BAD <3% of patients
HIT I is transient due to ___
clumping of platelets (actually an artifact)
HIT-I happens ___
immediately
HIT II is seen after ___ of heparin
5-10 days
in HIT II, platelet count falls by ____ from baseline
> 50%
HIT II is immune mediated by ____
anti-platelet factor 4
test for PF4
LMWH have a more favorable ___
benefit/risk ration
LMWH have predictable ____
dose response ratio
LMWH ahs ___ dosing
weight base
LMWH has less risk fo ___
HIT (if started initially)
LMWH (fractionated) has ___ administration
subQ
Available LMWH agent
enoxaprin (lovenox)
indications for LMWH
ACS treatment
DVT
PE
VTE prophylaxis in high risk populations
Dose of lovenox for acute DVT w/ or w/o PE (inpatient)
1mg/kg/dose (roundedO subQ q12h
OR
1.5mg/kg (rounded) subQ once daily
lovenox dose for acute DVT w/ or w/o PE (outpatient)
1mg/kg/dose (rounded) subQ q12h
vitamin k antagonists inhibit ___
post-translational carboxylation of coag factors II (prothrombin), VII, IX, X
vitamin K antagonists inhibit two vitamin k sensitive ___
synthetic enzymes
warfarin is reversed with ____
pharmacological doses of vitamin K (phytonadione; mephyton)
doses of vitamin K to reverse warfarin
2.5-10mg PO (5mg tablet)
1-10 mg IVPB (rare risk of anaphylaxis w/ rapid infusion)
vitamin K antagonists are often started with heparin for
Afib, DVT, PE
D/C IV heparin when ____
warfarin is therapeutic
warfarin takes ____ for full anticoagulation
5-7 days
when using warfarin, measure effects wiht ___ and ___
prothrombin time (PT) and international normalized ratio (INR)
Therapeutic INR ranges for Afib, DVT< PE
2-3
therapeutic INR ranges for mechanical heart values (NOT porcine)
2.5-3.5
each dose of warfarin takes ____ to take effect
~48h
complication of starting 10mg warfarin daily
possibility of warfarin induced skin necrosis
INR 3-5, no sig bleeding
lower or hold next dose
resume when INR nears 2-3
INR 5-9; no sig bleeding
omit next 1-2 doses. Monitor INR, resume when INR nears 2-3
INR >9; no sig bleeding
hold warfarin.
give vit k 5-10 mg PO
Monitor INR next 2-3 days, give addl vit k if needed
any increased INR; serious bleeding
hold warfarin
give vit k 10 mg via SLOW IVPB AND FFB
may repeat vit K IV q12h
any increased INR; life threatening bleeding
hold warfarin.
give PT complex & vit K 10mg IVPB (slow); repeat if necessary
drugs that inhibit CYP2C9 increase ___ an d___
INR and risk of bleeding
drugs that inhibit CYP2C9:
bactrim
flagyl
drugs that INDUCE CYP2C9 decrease ___ and INCREASE ___
INR and the increase the risk of thrombosis
drugs that induce CYP2C9
contraceptives
sources of high dietary folate
beef, pork liver
green teas
leafy green vegetables
spinich
___ is in prefilled syringes
Fondaparinux (Arixtra)
Anti-Factor Xa inhibitors is a ___
synthetic pentasaccharide
Anti Factor Xa inhibitors are mainly ___ eliminated
renally
Anti factor Xa inhibitors are contraindicated in ___
CrCl <30
unlabeled use of anti factor Xa inhibitors:
DVT px in patients w/ h/o HIT
oral direct Xa inhibitor
xarelto (rivaroxaban) Bayer
oral direct xa inhibitor w/ no lab monitoring
xarelto
recent reversal agent of xarelto
aadexant alfa
MC adverse affect of xarelto
bleeding
>5%
bivalent direct thrombin inhibitors
lepirudin
bivalrudin
desirudin
univalent DTIs
argatroban
dabigatran
DTIs may be used in pts w/ ____
h/o HIT II
used to treat HIT
argatroban
argatroban is given ___ and monitored w/ ___
IV; monitored w/ PTT
Argatroban is NOT ___
really eliminated. (used inpatients w/ HIT and poor renal function)
AZ withdrew application of Ximelagatran in ____
2006
Dabigatran requires no ____
lab testing
new reversal agent for dabigatran was released in ___
2015
dabigatran (pradaxa) reversal agent
idarucizumab (prdxbind)
idarucizumab is humanized ___
monoclonal antibody
MOA of Idarucizumab
binds to pradaxa
dosage of praxbind
two consecutive 2.5 g doses given IV
cost of PRaxbind
3,500$
decoy protein
factor Xa
Andexanet alfa corrects
apixaban rivaroxaban edoxaban enoxaprin fondaparinux
anti platelet drugs
glyprotein IIB/IIIa inhibitors
ADP receptor antagonists
others
eptifibatide is administered __
IV
purpose of eptifibatide
ACS
PCI and/or stent
abciximab (RepPro)
chimeric monoclonal antibody (human/murine)
abciximab has numerous ___
adverse effects
___ is rarely used
abciximab
___ has a black box warning
ticlopidine
ticlopidine is reserved for patients:
intolerant to aspirin
those who failed aspirin therapy
clopidogrel is a prodrug converted to ___
unidentified active metabolite
clopidogrel ultimately prevents ___
platelet aggregation
clopidogrel drug interactions:
decreased activity w/ PPIs via CYP2C19 inhibition
increased his of restenosis while on PPIs
prasugrel is more effective w/ ___
clopidogrel or ticlopidine
prasugrel has less inhibition by ___
PPIs
platelet antagonists:
aspirin
aspirin inhibits platelet aggregation by ___
acetylation of ADP receptor
(aspirin) acetylation of ADP receptor lasts ___
life of the platelet
benefits of aspirin are waited against adverse effects:
GI bleed (minimal at low doses) Tinitis (minimal at low doses)
don’t chew ___ aspirin
baby
mechanisms of dipyridamole
platelet aggregation inhibitor
vasodilator
dipyridamole is used w/ ___ in patients w/ ___
warfarin; mechanical heart valves (rarely)
dipyridamole is used as a ___ in CAD
diagnostic agent (persantine stress test) frequently
Available tissue plasminogen activators
alteplase (activase, cathflo)
tPA (alteplase) is used for
lysis of coronary artery thrombi in AMI
management of ischemic stroke (more common0
lysis of occluded ports of catheters
stroke dose of tPA (alteplase)
0.9mg/kg
load 0.09 mg/kg (10% of total dose) over one min; followed by 0.81 mg/kg (90% of dose) CIV over 1 hr
max dose of tPA
90mg