When to start warfarin after surgery
Management of Perioperative Anticoagulation – Please participate in our 3-minute survey below!
good morning everybody I'm going to talk
about the management of the parapet
Atlantic regulation today which leads me
to are the topics that we're going to
talk about we're going to go to do these
agendas and when is it actually safe to
perform a surgery without increasing the
risk of hemorrhage or from borer
embolism which leads me leads me to the
Cascade of the blood coagulation I guess
every one of us has tried to memorize
the blood coagulation cascade during the
medical school and it is a complicated
system so I thought we maybe go through
the important part of the coagulation
cascade in a short video as a memory
hook at the site of vessel injury
the first platelets arrived to start
sealing the wound simultaneously that
coagulation cascade with its various
coagulation factors is activated this
involves two pathways the extrinsic and
the intrinsic pathway
extrinsic activation begins with now
exposed molecules of the vessel wall
such as tissue factor which forms a
complex with factor seven finally
leading to the activation of factor 10
this factored 10a is the point at which
the extrinsic and the intrinsic pathways
of the coagulation cascade meet the
intrinsic pathway consists of various
coagulation factors activating each
other in a chain reaction at its set a
complex with an additional cofactor is
formed this complex now activates factor
10 since the two pathways merge at the
level of factor 10a this factor has a
pivotal role in the coagulation cascade
further down the Cascade factor 10a in
combination with 5a activate thrombin
and induces the so-called thrombin verse
one molecule of factor 10a can catalyze
the formation of a thousand molecules of
thrombin
these large amounts of thrombin caused
the further activation of platelets and
the enhanced formation of fibrin fibrin
then formed strands making up the mesh
that stabilizes the platelet plug in an
arterial clot and holds together the red
blood cells in a venous clot it can be
concluded that the central role of
factor 10a in the coagulation cascade
makes it a viable target for therapeutic
intervention in pathologically altered
blood coagulation which basically leads
me to the question for the residents you
know any possible targets for the
interpolation in the blood coagulation
cascade
well first you can antagonize the
calculation scientists of the effectors
like vitamin K for example or direct
antagonists of the factors like with our
before of factor 10 or to thrombin
absolutely correct so the possible
targets in the coagulation cascade are
mainly the coagulation factor synthesis
themself Judas group relaunch the
vitamin K antagonists and they also the
factor 10a in division like the low
molecular weight heparin Dan operate
under par Enochs rivaroxaban apixaban
and also it looks a van and
unfractionated heparin and we do have
the factor 2a which is the thrombin
himself inhibition through the until do
the double gate Ron vivo ruby Dean I
guess Rubin on also unfractionated
heparin the effects and the antithrombin
dependency can happen in a direct or an
indirect way we do have those both
groups the directly inhibition the
effects of the antithrombin dependency
can happen through their rivaroxaban
apixaban Eric Subin Debbie Catz Ron and
in the endo dire keyway as you can see
through the Donna permit and from the
products and also Judy heparins the
atmost administration way can be in all
way and in a peripheral way there is
also a classification in the
anticoagulants er groups and we do have
also the way of monitoring them
typically we do money toward a vitamin K
antagonists the unfractionated heparin B
value Ruby Dean and I got Rabanne and
occasionally we can also monitor
rivaroxaban epics Savannah Eric's a van
der bigoted Ron and the rest of illicit
substances here and there is also the
way to separate them in groups that we
have specific antidotes for them the you
have a curently
antidote specific antidotes for vitamin
K antagonists unfractionated heparin LA
molecular weight heparin and Debbie get
Ron and they are also specific antidotes
they are they're not available or they
are not available yet for the
rivaroxaban apixaban eric Subban and
also for the apparent apparent nukes and
the rest of the listed substances here
and there is also the matter of the
half-life of this medication we do have
medication bitsy basically substances
with a short half times something about
30 minutes up to three hours and we do
have some of them that they have
intermediate half-life like rivaroxaban
apixaban Eric Savannah and Debbie get
Ron something about for up to 10 hours
and there are some of them that they
have a long half-life like here down
operate or from the parent nooks with
over ten hours if you do have also the
antiplatelet drugs the substance can be
separated into groups who
inhibits the cox-1 enzyme in an
irreversible way as is aspirin and we
have the adp receptor inhibitors like
clopidogrel and procedural and the rest
of the listed
substances and also the gluco protein to
be and 3a antagonists like ab c map and
t ro fear on this substance they're the
most important substances therefore the
energy calculation has been listed here
as we can see they have a really
different level of the half-lives for
example different Pokemon has a
half life something about 80 up to 240
hours and the pre last one B while in
routine has a half life something about
thirty minutes which is really low and
there is also the matter of the
accumulation of these substances by
renal insufficiency as some of them did
you not accumulate some of them they
have a really high liver and
accumulation as you can see by aw got
Ron and there's also the matter of this
tip if it's specific antidotes we do
have for example for those four
underlines substances which belongs to
the direct oral anticoagulation we do
have specific antidotes like here and
extranet
and basically because of the limited
time I will be focusing of the dorks of
the direct oral anticoagulation and the
direct oral anticoagulation can be
separated in two groups the diet or
thrombin which is the factor 2a
antagonists and also the direct oral
factor 10a antagonists she'd be no dduba
gastrin as the products and also
rivaroxaban a sterile so is there's a
commercial name and also a pizza ban as
Italy Chris and Eric Savannah and
Louisiana they have been made the um
basically phase 3 clinical trials for
the important indication for those
medications we do have basically
approval for a vein of thromboembolism
prophylaxis after orthopedic surgeries
for Dobby get Ron rivaroxaban and
apixaban an Arab Subhan in the those
listed trials and also for embolism
prophylaxis buyouts real defibrillation
and acute treatment and secondary
prophylaxis of vein or thermo embolism
and there are also other clinical trials
that they are still undergoing for other
indications for example the secondary
prophylaxis after acute coronary events
for rivaroxaban that's the athletes
trials and there is no approval yet for
this indication for the thromboembolism
Rhambo prophylaxis by a cutie a medical
patient for rivaroxaban we found out in
the Macklin study basically that there
is a
bleeding rates and so no approval for
this indication during no trials and no
approval in the general surgery for this
indication and also about the mechanical
heart welfare proteases for add a bigot
Ron the there is a higher embolism and
bleeding rates than the vitamin K
antagonists which is in intercondylar
which is a contraindication for for this
one so basically the current approval in
Switzerland for the dorks are for the
vino thromboembolism prophylaxis only in
the orthopedic surgery or general in
orthopedics procedures for rivaroxaban
and apixaban for venous thromboembolism
there is for rivaroxaban apixaban Eric
Subban and also for Debbie got Ron well
I have to say that in the cases of E dr.
van and Debby guitar on the D started
basically to giving the patient the it
looks abandoned Debbie got Ron after
initial parenteral anticoagulation over
five days and also Ferranti for LGA
fibrillation there is a current approval
for rivaroxaban epoch seven and Eric C
bon giorno approval for vino
thromboembolism prophylaxis in general
surgery cardiac bought proteases
pregnancy or patient or undergoing a
lactation period so there are practical
aspects about the dorks the preoperative
time interval the antagonizing by
bleeding in specials in emergency
interventions and the way of monitoring
them the surgical intervention so
basically the in the most
intervention is suspension over 20 hours
is enough for this group of medication
it means that the patient has to take
his last medication something about two
days before the operation in the case of
the high-risk operation like in the
central nervous system or a general
surgery to recommend to suspend the
medication over 48 hours before the
operation
the is the matter of the longer leading
time by a kidney
see especially by in case of W Tron
which accumulates really high in by
kidney insufficiency so there is not
recommend that and to take his education
for patients with kidney sufficiency or
we have to stop or suspend the
medication over ninety six hours before
the operation
they are definitely lower be leading
with its care for the smaller
intervention like in the dentistry or
skin biopsy and there is no suspension
needed and if there is any further
testing needed to check the anti factor
ten activity we have options with anti
factor ten eight Tests or from being
time so I have also to say that the
preoperative bleeding risks have not
been investigated systematically in this
matter there is a for example in the
case of your rivaroxaban we can see um
do recommend to stop the basically de
medication to suspend the medication at
least 24 hours before the surgery you
can start to take the medication one day
after the surgery which is a risky thing
there are experts who think that we have
to stop almost two three days before we
start the medication to take a
rivaroxaban postoperatively or we if
there is necessarily we can start
bridging with heparin there is
definitely the problem with the bleeding
if we start with anticoagulation really
really shortly after the operation so as
you can see in this case we can have a
higher bleeding risk for example in this
case of there a kidney transplant here's
the neutralization of the drugs we do
have specific antidotes dabigatran has a
specific attitude which is either a root
system up and the factor 10a antagonists
like and x annette the short half time
of the dorks
is really beneficial so basically after
a short time on the level the
concentration of the substances in the
blood going to be so low that the
effects are gonna be also lower than the
rest of the medication which have a
really higher half-life time
in there is also there is also the
possibility to take dialysis Dobby gets
Ron we can do an initial dialysis and
there is also the matter of restitution
we can receive it with a volume of 60 up
to 70 liters for rivaroxaban and
apixaban they are really highly bounded
proteins so the dialysis is not really
promising in those substances so what we
do in the case of the bleeding there is
the question what medication did take
the patient with what dosage and what
was the indication and of course the
question when was the last time that the
patient took the medication
the Picts theorem as I said is is almost
arrived at about two up to four hours
after the medication and to the rapid
reduction because of their really short
half time is beneficial for us and there
is also the matter of the monitoring of
the peak serum which anti factor 10a and
also factor anti factor to a test or
thrombin time if you have a slight
bleeding so there are symptomatic
measures to take for example local
measures or application of a trend exome
it assets or in general the postponing
the next dose of the medication or we do
have substantial bleeding of course
discontinuing the medication is
recommended and emergency matters and
also hospital admission if there is
opposed to if they also taken patients
the antidotes for these drugs basically
are the prothrombin complex concentrate
we knew that as a very Plex or pro-trump
Lex and also there is a recombinant
factor 7a which is novo 7 and this
specific antidote as I stated before for
W at Ron which is it all resume up and
factor 10a antagonist which is the
inactive factor 10 molecule as we can
see those graph they on your left-handed
side there they are basically sampling
the
a lot of the patient over 24 hours and
testing the thrombin time patient with
undergoing a procedure but basically on
the left-handed side the patients are
taking it very sumup by bleeding and on
your right hand outside the are patients
who are undergoing an emergency
intervention and as we can see basically
the level of the thrombin time is in a
group who are under odorous to sum up is
lower in general in its first 24 hours
than in the group without taking the
leaves antidotes and there is a peak
after four hours about something about
hundreds seconds of the thrombin time in
the group without taking these antidotes
and here basically on the left-handed
side there is a pixie bond and the
right-hand side is a
rivaroxaban here is also it have been
given the Civic antidotes anti factor
ten antidote which is on the extranet in
the in the graph a they basically give
their antics on it other bowls and in
this C to give it as a bolus and as an
infusion and to compare to patient
taking this antidotes with the placebo
group and on the right hand side there
is the same procedure via TV rivaroxaban
and as you can see basically the anti
factor ten activity is with the Bowls in
general for the first two hours lower
than in the placebo group and if we add
in infusion with this the specific anti
factor 10a we have a we have a longer
time with a early law anti factor ten
activity up to four or five hours we
have an algorithm at the University
Hospital in the ER which has been
established in the last years if we do
have a patient in the ER who is taking
anticoagulants and we do not know which
medication is it so we do have the
possibility to check the quick and enr
and the thrombin time and the anti
factor ten activity and if you go
through these basically lab tests you
the vitamin K antagonists they have an
influence of E&R which is going to be
higher if the patient only have a thump
in time the thump in time is higher so
basically he might have taken Dobby get
Ron and if only the anti factor 10a and
sometimes in air is higher so basically
he's been taking the factor 10a
antagonists this is a really short
review about the anticoagulants and Jo
indication what if liberal film bosses
and long game Buddhism for the for
heparin and Pinter's are high rates and
also for about the atrial fibrillation
and prosthetic heart valves there is no
indication for funder products in that
case and for the vitamin K antagonists D
for the atrial fibrillation and the
prosthetic heart valves there's still
the therapy of first choice and but we
can also give to patients so we came in
k antagonist in them in the matter of
report from bosses or lanka embolism
and about the oral factor 10 inhibiting
inhibitors and from been invaders the
are indications so further approval for
the indication such as a favorable
embolism and lung embolism and arterial
fibrillation but you're no approval for
a prosthetic heart valves for those
groups so we safe to perform surgery
without increasing the risk of
hemorrhage or thromboembolism the answer
to this question is is is really
complicated because there are a lot of
factors that they have influences in
this matter so the American College of
Chest Physicians proposed guidelines
especially in the eighth and then ninth
edition but the anti Ron Baker
prophylaxis in patients with different
risk factors so thank you for your
attention
well thank you very much enjoy the movie
very much what we understand is that
it's very complicated there's a lot of
drugs associated with that so I must say
that I try to follow everything he could
not follow all this medication when to
use it when not to use it it said one
factor is the economy based on that the
cost of TC so that I'm very expensive
maybe you want to make a comment or if
you know what are the cost associated
with with this or the economy can SPECT
of this and the other question very
simple questionnaire you did not speak
much about aspirin not sure so and
that's what we have most common many
people take aspirin low-dose aspirin now
sometimes they say sometimes they don't
say should we completely ignore that for
all surgery what should we do in this
situation I mean typically we has to
start a week before or five days before
maybe tell us and the two most common I
think I uses a spin in the clopidogrel
that we can see a maybe just simple
recommendation for this to anticoagulant
that are widely used in the population
and people who donate specifically a
risk at least once be absolutely so for
example I knew that from the cardiac
surgery that it depends on the update
indication that the patients taking
those medication they're taking aspirin
for example but you stopped taking
clopidogrel several days before and we
try to bridge that with low molecular
weight heparin or with heparin himself
if the patient are at the hospital but I
guess it is mostly depends on and they
and this under surgery if if there's a
higher risk of bleeding so we can stop
the Peter trip for sure but the aspirin
is I guess in every clinic
in every clinic is different how are
they handling this as a rule in patients
with a high cardiovascular risk we would
not usually stop aspirin we would
continue aspirin and whether or not we
stopped clopidogrel or another ATP
receptor antagonist
depends on the risk so on
the rate of the the latency from
standing for example whether it's within
three months three to six above six
above twelve months since the stent was
placed and there is an algorithm which
was published by the mestizo which is
available in the internet too
to give an orientation on to a platelet
antagonists another question in some
major surgery or liver transplant we
ever tried to have this patient may
bleed and we use routinely even in
high-risk the saqqaq up for antitrump
oolitic a generally tambien agent what's
the risk associated with strombolis in
these cases I would consider the risk as
being very low we would not usually give
it in cases of hematuria in order to
prevent a clotting we would not usually
give it in disseminated intravascular
coagulation and people not usually give
it when there is external circulation
but otherwise I would think the risk was
from boses triggered by these are
different ratings is very low one
question is you know if I compare this
to chemotherapy we see now much more
trucks for anticoagulation so it's like
we had five a few to 15 years before
only for corded only one truck now we
have plenty saying that tool you know
the patient comes into the emergency
room you enter let's say you know the
the numbers quick and platelets and then
then you ask for risk medications and
then tools would basically come up with
choice number one to reform because I
could imagine in 10 years we have 20
this is one question and the other one
is our way it goes is similarly go be is
there anything in this area where you
also go to a more personalized approach
that means you know what we do for
cancer we know some patients want better
to this drug compared to the other one
it is a developing field there is no
such algorithm but of course we take
several factors in account for example
renal insufficiency liver insufficiency
whether it is a patient with an active
tumor or not and the like so for example
an active malignancy first choice would
be low molecular heparin regarding two
available studies and now as a first and
so far only one of the direct Antico
grams doxepin Dixie Anna for which very
recently non-inferiority has been shown
compared with low molecular heparin
studies ongoing for the other dogs I
would expect all of them to be available
for malignancy we tailor which
anticoagulation we use for certain
patients of course but there is as far
as I know no such algorithm so it is
kind a sort of a personalized medicine
which we apply of course Oh Gabby got
Ron we would we would not like to use it
in the patient with renal insufficiency
because it accumulates and most of
bleeding's bring complications or even
deadly bleeding complications have
occurred because this has not been taken
into account thank you very much for the
detailed presentation I have a question
on my own we see a good number of tests
now who come to surgery with one of the
newer anticoagulants Revo hooks Ebonics
rlto orally Chris and the question
always comes up how many days before
surgery do we need to stop these
medications and what do we need to
measure when do we need to bridge with
heparin or low molecular weight heparins
is there an algorithm mr. and easy rule
for us to follow it is quite simple
because the standard case is that you
would not have to bridge preoperatively
in patients without a very high risk of
bleeding or with substantial renal
insufficiency
you would give the last dose at die a
day - - so
with a distance of more than 24 hours in
selected cases I would give or consider
preoperative low molecular weight
heparin at the prophylactic dose for
example the evening before the operation
but the standard cases that you would
not need a preoperative bridging for
patients with a natural fibrillation you
would not need a bridging at all so this
applies only for venous thromboembolism
just had a short comment because you
were showing a patient with a kidney
transplant just to let you know that
patients on the waiting list for liver
kidneys in Zurich are not allowed to be
on directorial anticoagulants because of
emergency planned operations okay have
to be on not come up so thank you so
much
