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


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


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


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


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


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


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


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