18: Anticoagulant toxicity Flashcards
what is the INR target for mechanical heart valves, aFib and VTE
mech valves = 2.0-3.5
AFIB and BTE - 2.0-3.0
what is defined as minor bleeding
trivial bleed that resolves within 20 minutes
what is defined as a major bleed
bleeding into critical organ or a decline in HgB 20g/L (requires transfusions (1 pack of blood ~10g/L)
CBCs should be done _________ for those on anticoagulants
yearly
which is more easily treated? bleeds or clots
bleeds
what is the most feared bleeding complication
intracranial bleed
which 2 types of intracranial bleed is typically due to trauma in the elderly but prognosis is typically good
epidural or subdural hematoma
which of the following has worse prognosis
1. epidural hematoma
2. subdural hemoatoma
3. subarachnoid hemorrhage
4. intracerebral hemorrhage
5. 1+2
6. 3+4
6
why are intracranial hemorrhages so dangerous
Fixed space (within skull), concern with initial volume and expansion of bleeding
hemorrhages on anticoagulants have higher (3)
initial______
risk of _____
severity/ probability of ____
initial volume
risk of expansion
severity/ probability of death
DOACs reduce risk of aaICH by ________ compared to warfarin
30-70%
compared to warfarin, DOAC ICHs have (3)
______ volumes of blood
less severe ______/ more functional recovery
fewer ____s
smaller volumes of blood
less severe strokes/ more functional recovery
fewer deaths
what is the msot common extracranial bleed
GI
in extracranial major bleeding from ACs
1. majority result in full recovery spontaneously
2. requires reversal or interruption of treatment
3. the most common area is the lungs (pneumothorax)
4. none of the above is true
2
DOACs ___________ compared to warfarin
1. decreases both ICH and GI bleeds
2. increases ICH and decreases GI bleed
3. decreases ICH and increases GI bleed
4. increases ICH and GI bleeds
3 (but increase in GI bleeds is not stat sig)
T or F: high bleed risk score is not a reason to avoid anticoagulants
T
in ____, thrombotic and bleed rsk often rise in parallel
AF
what 6 things must you do for assessment of bleed
location
timing of blood loss
quantify and qualify blood loss
immediate mnagement
future management
impact of major bleed vs clotting event
generally, what is a good time to restart anticoagulation tx
____ usually
_ week if cause of bleed identified and rectified
_____ wks if conservative approach
2wks usually
1 week if cause of bleed identified and rectified
2-8 wks if conservative approach
observational data shows that restarting AC after GIB ____________________________
reduces risk of thrombosis and mortality and doesn’t increase risk of recurrence
observational data shows that restarting AC after ICH ___________________
decreases risk of ischemic events and mortality + no differences in major bleeding
critical INRs are defined as
INR >5.0
WHO requires labs to perform quality assurance testing between INR ________
1.5-4.5 only
what are 4 general categories of factors that elevate the INR
______ in health
changes to ________
changes to ______
administration of_________
deteriorations in health
changes to medications
changes to lifestyle
administration of too much warfarin
what changes in lifestyle may affect INR
vit K intake
alcohol consumption
level of activity
induction/ inhibition of this CYP enzyme causes major changes to INR ___________. minor changes occur with ___ and __________
2C9 = major
minor = 3A4, 1A2
IV vit K admin for warfarin reversal is used in ___________ and takes affect in _____________
life threatening situations
6-12hrs
oral vit K is used in ________ and takes effect in ______________
nonemergency situations
16-24hrs
what 2 routes of vit K should be avoided
IM and SQ
typical ER dose of IV vit K
10mg
in a pt with INR 4.5-10.0 guidelines suggest
_______ routine use of vit K
- can you “consider” vitK?
against routine use of vit K
hold 1-2 warfarin doses and consider vit K PO 1-2.5mg and reassess INR
in a pt with INR >10, guidelines suggest
hold warfarin
vit K PO 2-5mg and reassess INR
PCC reverses INR within
minutes
after a critical INR has been managed and the acute, reversible cause identified, what action should take place?
document INR <4
implement warfarin dosing similar to that prior to the cause occured
after a critical INR has been managed and the acute, non reversible cause identified but will continue, what action should take place?
document INR <4
empirically decrease warfarin dosing based on experience/ literature
after a critical INR has been managed and no identifiable reason has been found what action should take place?
document INR <4
depending on clot vs bleed risk, reduce maintenance dosing accordingly (typically ~10% decrease but individualize based on pt)
PCC is derived from ______ and administered by _________
human plasma
IV infusion
PCC contains factors ___________ and protein ____________
factors 2, 7, 9, 10
C, S
PCC reduces INR within minutes but the effect is not sustained, _______ must also be administered to sustain reversal in INR
vit K (~10mg)
PCC indications (2)
Serious or life threatening bleeding
Requires urgent (<6hrs) interventions with risk of bleeding
aPPC contains _____________ and is mostly used in ___________
activated factor 2a (i think it’s atually 7a….)
hemophilia patients
rank the DOACs based on renal elimination
dabig > edoxi > rivaroxi >apixa
which DOAC can be removed by dialysis
dabigatran
there may be an accumulation of DOACs if
overdose, acute renal failure, DDI (strong P-gp inhibitor for D and E, strong P-gp + 3A4 inhibition for R and A)
when would DOAC reversal be needed
major bleeding or urgent need for procedure
acute ischemic stroke (and desire for thrombolysis- off label)
antifibrinolytisc MOA
inhibit fibrinolysis by preventing conversion of plasminogen to plasmin, plasmin then can’t act on fibrin to clot
T or F: antifibrinolytics are antidotes for DOACs and warfarin
F- doesn’t make clots, only blocks their break down
what are 2 practiacl uses of antifibrinolytic agents
topical if dental/ nasal bleeding, oral if heavy menstruation or IV in operating room
dabigatraan antidote is __________, which is a _____________ that binds ________ to dabigatrain with 350x stronger affinity than thrombin
idarucizumab
enginerred antibody fragment
noncompetitively to dabigaatran
idarucizumaba is indicated for adult pts treated with dabigatran when
rapid reversal of anticoagulant effect is required for emergency surgery/ urgent procedures or life threatening or uncontrolled bleeding
what is the antidote for factor Xa inhibitors
andexanet alfa
andexanet alf is a _______________ that acts as _________ with high specificity for both oral and injectable Fxa inhibitors
modified recomb factor Xa
competitive decoy to target and sequester
andexanet alfa is catalytically _____
inactive
