Venous Thromboembolism
Summary
TLDRThis lecture delves into the management of Venous Thromboembolism (VTE), emphasizing the importance of early diagnosis, risk assessment, and anticoagulation as the cornerstone of treatment. It highlights the role of sulodexide as a novel agent for secondary prevention of unprovoked VTE, showcasing its safety and efficacy in reducing recurrence rates without significant bleeding risks. The talk underscores the need for individualized treatment plans, considering patient-specific factors and the balance between prevention and bleeding risks.
Takeaways
- π Early diagnosis is crucial in managing Venous Thromboembolism (VTE) due to its life-threatening complications, including high risks of death and recurrence.
- π Identification of symptoms and risk factors for Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) is essential for prompt treatment.
- π©Ί The use of diagnostic tools like compression ultrasonography and CT pulmonary angiography (CTPA) is vital for assessing the risk and confirming the presence of VTE.
- π Anticoagulation is the primary treatment for VTE, with decisions on its duration and intensity based on the patient's condition and risk of bleeding.
- β³ The duration of anticoagulation therapy is a critical decision, with guidelines suggesting indefinite continuation based on patient risk factors.
- π‘ The risk of recurrent VTE remains significant even after the cessation of anticoagulation, necessitating ongoing evaluation and management.
- π The natural history of VTE often involves recurrence, highlighting the importance of secondary prevention strategies.
- π Suludexide is a novel drug studied for the prevention of unprovoked recurrent VTE, offering a different mechanism of action compared to traditional anticoagulants.
- 𧬠Suludexide's unique affinity for the endothelium and its role in restoring damaged endothelium make it a promising option for secondary prevention.
- π The SURVEY trial demonstrated the efficacy of suludexide in reducing the recurrence of unprovoked DVT without major bleeding episodes.
- π Individualized treatment plans for VTE are essential, considering factors such as cost, patient comorbidities, and bleeding risks.
Q & A
What is the primary reason for continuing anticoagulation therapy for an extended period?
-The primary reason for continuing anticoagulation therapy for an extended period is to prevent the recurrence of venous thromboembolism (VTE), as large veins in the lower extremities often remain partially blocked by blood clots that are not fully reabsorbed, leading to an increased risk of recurrent thromboembolism.
Why is the natural history of VTE considered problematic?
-The natural history of VTE is considered problematic because it tends to recur frequently. Both provoked and unprovoked VTE have significant recurrence rates, with a recurrence rate as high as 40% for femoral deep vein thrombosis (DVT) within 10 years post initial treatment.
What are the potential risks associated with indefinite anticoagulation therapy?
-The potential risks associated with indefinite anticoagulation therapy include an increased risk of bleeding. The decision to continue anticoagulation must balance the risk of recurrent VTE against the risk of major bleeding.
How does sulodexide differ from other anticoagulants?
-Sulodexide differs from other anticoagulants because it is not a traditional anticoagulant but rather a compound that inhibits thrombin generation through its components, heparan sulfate and dermatan sulfate. This mechanism makes it a milder and potentially safer option for preventing recurrent unprovoked VTE.
What were the findings of the SURVET trial regarding sulodexide?
-The SURVET trial found that sulodexide significantly reduced the recurrence of DVT by 49% compared to placebo, without increasing the risk of major bleeding. This trial demonstrated the safety and tolerability of sulodexide for the prevention of recurrent unprovoked DVT.
What is the recommended duration for initial anticoagulation therapy for VTE?
-The recommended duration for initial anticoagulation therapy for VTE is typically 6 to 12 months. However, the decision to extend treatment beyond this period should be based on a patient's individual risk factors for recurrence and bleeding.
What are the benefits of using NOACs (novel oral anticoagulants) for extended VTE treatment?
-The benefits of using NOACs for extended VTE treatment include their efficacy in reducing the recurrence rate of VTE and their relatively low risk of major bleeding compared to traditional anticoagulants like warfarin. Studies like the EINSTEIN CHOICE trial have shown that NOACs such as rivaroxaban can be effective for extended VTE treatment.
Why is individualized treatment important in managing VTE?
-Individualized treatment is important in managing VTE to account for each patient's unique risk factors, including the location of the thrombus, comorbidities, bleeding risk, and personal preferences. This approach helps to optimize treatment efficacy while minimizing the risk of adverse effects.
What is the role of endothelial dysfunction in VTE management?
-Endothelial dysfunction plays a significant role in VTE management as it is a key factor in the pathogenesis of thrombus formation. Improving endothelial function can help reduce the risk of recurrent VTE, making it an important target for both acute and extended treatment strategies.
What are some key considerations when deciding to extend anticoagulation therapy beyond the initial treatment period?
-Key considerations when deciding to extend anticoagulation therapy beyond the initial treatment period include assessing the patient's ongoing risk of VTE recurrence, their risk of bleeding, the presence of comorbid conditions, and patient preferences. Regular reassessment and individualized decision-making are crucial in this process.
Outlines
π©Ή Anticoagulation in VTE Management
The first paragraph discusses the complexity of treating Venous Thromboembolism (VTE), emphasizing the importance of anticoagulation therapy. It highlights the decision-making process regarding the continuation or cessation of anticoagulation, which may be indefinite depending on the patient's condition. The summary points out the natural history of VTE, which often involves recurrence despite the body's healing mechanisms. It also discusses the high recurrence rates of VTE, even years after the initial treatment, and the dilemma of balancing the benefits of extended anticoagulation against the risks of bleeding. The paragraph introduces suludexide as a drug studied for preventing unprovoked VTE recurrence, distinguishing it from other anticoagulants by its mechanism of action involving heparan sulfate and dermatan sulfate, which target antithrombin III to inhibit thrombin generation.
π Suludexide's Role in Preventing Unprovoked DVT Recurrence
The second paragraph focuses on the use of suludexide in preventing the recurrence of unprovoked deep vein thrombosis (DVT). It describes a multi-centered, randomized, double-blind, placebo-controlled trial conducted in Europe, where patients were given either suludexide or a placebo after 3 to 12 months of regular anticoagulant treatment. The results showed a significant reduction in the recurrence of DVT with suludexide, without major bleeding episodes. The paragraph also explains the unique attributes of suludexide, being part of the glycosaminoglycan family but with distinct active agents, particularly its heparan sulfate component that has a strong affinity for the endothelium. It touches on suludexide's protective and restorative effects on the vessel wall and its role in managing endothelial dysfunction.
π Key Points in DVT Management and Prevention
The third paragraph summarizes key points from the lecture on DVT management, emphasizing early diagnosis, risk assessment, anticoagulation as a core treatment, and the importance of individualized treatment plans. It stresses the need for early recognition of DVT symptoms and risk factors, the use of diagnostic tools like compression ultrasonography and CTPA, and the decision-making process for long-term management and prevention. The paragraph also mentions the role of suludexide as an additional option for secondary prevention of DVT recurrence and the necessity of considering factors such as cost, patient comorbidities, and bleeding risks when tailoring treatment plans.
Mindmap
Keywords
π‘VTE
π‘Anticoagulation
π‘Recurrence
π‘Fibrinolysis
π‘DVT
π‘Reassess
π‘Sulodexide
π‘Glycoproteins
π‘Endothelium
π‘Risk Factors
π‘Individualized Treatment
Highlights
VTE treatment is not complicated and involves primary and secondary treatment decisions, including the choice of anticoagulation.
The recurrence of VTE is a significant issue, sometimes requiring indefinite duration of anticoagulation depending on the patient's case.
The body heals by fibrinolyzes, absorption, and recanalization, but not all blood clots are reabsorbed, leading to a risk of thrombosis recurrence.
Natural history of VTE often involves recurrence, with rates as high as 40% in large veins of the legs even 10 years post-treatment.
The decision to continue anticoagulation beyond 6 months is based on the patient's risk factors and the potential for bleeding.
Pixabban and rebaroxabine are studied for extended VTE treatment, showing reduced recurrence rates compared to aspirin without significant bleeding.
Suludexide is a unique drug studied for preventing unprovoked VTE recurrence, working differently by targeting thrombin generation.
The SURVEY trial demonstrated suludexide's effectiveness in preventing unprovoked DVT recurrence with no major bleeding incidents.
Suludexide's safety and tolerability include no dose adjustments, no iron monitoring, no dietary restrictions, and no significant adverse events.
Suludexide is part of the glycosaminoglycan family and has unique properties for repairing and restoring the endothelium.
Endothelial dysfunction plays a role in VTE pathology, and its management is crucial for optimal VTE prevention.
Acute VTE must be managed with anticoagulants, and decisions for long-term management and prevention should be reevaluated every three months.
The importance of early recognition of VTE through certification and testing to identify high-risk patients for DVT.
Risk assessment using D-dimer testing can direct management decisions for suspected VTE, such as CTPA or compression ultrasonography.
Anticoagulation is central to VTE treatment, with considerations for when to anticoagulate, especially in proximal DVT and those with risk for extension.
Treatment for VTE should be highly individualized, considering cost, location of thrombosis, patient comorbidities, and bleeding risk.
Suludexide is a promising addition to anticoagulants for secondary prevention of unprovoked VTE, with a lower risk of bleeding.
Regular assessment of patients' risk using tools like HAS-BLED can help in managing anticoagulation therapy effectively.
Transcripts
the VTE is not complicated okay
so from there the primary treatment
you will have the secondary treatment
which is actually the decision to anticoagulate or not
because this is actually
but you know you have recurrence
that's the issue
so it's either sometimes indefinite duration
depending on the case of the patient
so this is the summary
so if you can have all these things known
that is a slight very important not to miss okay
so why is it important to continue anti coagulation
for a long time even in the primary treatment
it is because of this large
where the nostrombos is present
in most of the veins of the patient
in this example
most of the time in the lower extremities
look at these large veins full of blood clot
from top to bottom
our body is the one doing the healing by fibrinolyzes
and absorption and finally recanalization
but the truth is not all blood clots are reabsorbed
and therefore the veins are not fully recanalized
therefore there is still areas with the wounded
and the scilla linings
and therefore more prone for recurrence of thromosis
DVT baguettes DVT okay
so Vito stromboembolism does not have a happy ending
sorry the natural history of VTE is more of recurrence
in the following months or years
after ancient treatment recurrent VTE
for both provoked and unprovoked
VTE is seen here as very significant
as high as 40% in in your femoral DVT
bigger veins nor of the of the legs
as even as long as 10 years post initial DVT treatment
hence the issue of continuing on anticoagulation
as secondary treatment after 6 months
when do we stop the treatment
or is it common to just continue anticoagulation
indefinitely
at the cost of increasing the risk for bleeding
you can see here that whether the patient is
is assigned to discontinue after 3 months
there is an increased risk for recurring VTE
ah those assigned to continue anti coagulation
the recurrence is delayed for like 3 to 9 months
but still the risk is increased
and therefore the conclusion is that
whatever the duration of anti coagulation
the risk of recurrent DTE appears to be the same
after anti coagulation is stopped
hence this is
the rationality behind most guideline recommendations
to reassess evaluate
and possibly continue anticoagulation indefinitely
depending upon the patient's risk factors
let's go back to our previous line
secondary treatment is all about extension of anti
cogulation after 6 to 12 months of primary treatment
the question will be always be
how much risk will the patient have
if anti cogulation will be extended for longer
periods of time the pixabban
this is a pixabban for extended treatment for VTE
and same is done for rebaroxabine
in the Einstein choice in this trial
recurrence rate is a significantly
the rest uh with 10 to 20 mg of rib river oxide
as compared to aspirin
and major bleeding for both doses are not
much as well not much bleeding
still a lot of positions are skeptics
in terms of continuing no wax
because of the fear of bleeding
this has always been the Achilles heel
of all antipoagulants now
reviewing the mechanism of action
of most of these antiquagulates
it's on the inhibition of factor 10
a look at this
not affecting intrinsic and intrinsic pathways
the bigotran in the beloridian
are direct from being inhibitors
and all these are actually powerful antiquagulates
now the another drug that is
been studied for the prevention of recurring
unprovoked BTE is that of suludexide
the difference with the previous antichoogulant
is that suludexide is not an anti
it's not an Aqua antiquagulant
because the fractions of suludex side
the fast moving heparan sulfate and a dermatan sulfate
are are on the anti thrombin 3 inhaparinco factor
which ultimately inhibits thrombian generation
and this contrast
with the direct action of the other antichroagulants
so in that sense
the anticoagulant effect of suludexide
on thrombine inhibition seems to be
quote unquote friendlier or milder
and this is the reason for the survey trial
that lost than and published in circulation
the survey trial is the use of suludexide
are not in acute DVT
but on the prevention of recurrence of unprovoked DVT
this is actually done in Europe
now you can see all the countries that multi centered
randomized
double blind parallel group placebo control trial
after 3 to 12 months of regular anticoagulant treatment
patients were
either given placebo with compression therapy
or solidarcide at two capsules
or 500 lipocemic units twice daily for two years
the result is a significant drop
in the recurrence of DVD
49% relative risk reduction in in favor of solidexide
and there are no episodes of major bleeding
in both solar deck side and of course
the placebo group
bleeding only occurred in two patients for each group
and you can see that this group's number
about 300 patients per group
so the conclusion is that of solar deck sides
safety and tolerability no dose adjustments
no iron are monitoring no dietary restrictions
no non drug drug interactions
no significant adverse events
in the
good news is that no major bleeding in patients
for whom you want to prevent recurrence of unprovoked
BTE so going back to my previous life
this is a summary of the BTE management
from the initial treatment
all the way to the extended treatment
there is another drug that should be added here
and that is that to the site
for the prevention of recurrence of unprovoked DVD
given two capsules twice daily
so what is suludexide
it is part actually of the gag family
that is composed of heparin and low molecular heparin
but suludexide is different
it is two active in agents
what makes it interesting is that the heparan sulfate
that I mention that is part of the glycopalics
is actually almost the same in terms of its component
no it's the
fast moving heparin of solar dixide is an analogue
of the heparin sulfate guards in the glycocalex
therefore because of this nor
they were able to show that
by radioactive labeling of the drug psuludexide
that it has a strong affinity
and unique affinity to the surface of the endosilium
rather than plasma proteins
and therefore
being able to restore the damaged endosilium
now I don't have any time to talk about the other uh
activities of uh Soludek side
suffice to say that the activity on the vessel wall
it uh
is protective and restorative of gods negative charges
down regulation of CRPs
inflammatory interlucans and NPS
and clump complement factors
to discuss on blood flow activity
being antithrombotic and hemoral chemorelogic
maybe next time around I will talk about it
so important concepts now to
to remember in the endocial dysfunction
exist in all aspects of the vercos
try and pathology
implication for prevention of endocial function
dysfunction is for optimal beauty management
in hospitalized patients
acute BBT has to be managed properly
with antitical arguments
but there has to be a decision for VTE
extension treatment depending on each case
which has to be re evaluated like every three months
and it's also involving patients decision
there is still the need for optimal improvement of
endicular dysfunction even that previous do be d
is one of the highest risk
for directors of second episode of DVD
and me
so with that thank you very much for your attention
hey so okay
thank you very much doctor
then zone in doctor
allow for that very extensive lecture regarding BTE no
it's managed it's uh
guiding starting from the recognition to what
the management of BTE you know
so we'll start with the reactions for no
for the lectures okay
so so for my points now so
it's very important that we early recognize Bde
through the certification and testing
you know so
if ever it's low or intimate marriage risk to do the d
diamber then eventually
we could hit the patient as high risk for DVT
for Bde then we could go ahead with sonography
you know immediate management by your anti
coalbulation of character
directed therapy is also important and but
but before
we manage this patient
is also to see that the risk of bleeding
knowing giving this antiqual relations
the same time uh
the decision for long term management and prevention
as well as control of other respect is also important
in this in this patient
doctor organcino
source of mention one medication which is solidexide
which has proven benefit in management of Bde
through repair of glycolics
which are microstruction
to maintain in the integrity of the indothelium
and at the same time lesser risk of chance of bleeding
compared to antagogulation okay
so I thought of the other points
can discuss guess electro
the the the lectures are all very insightful
I will make four points and as my reaction No. 1 um
early diagnosis is quite crucial in BTE as we know
this is a disease with life strategy complications
you know death
as well as recurrence can be as high to 30 to 40%
so prop identification of et symptoms are we got um
in DVT and PE and risk factors are quite essential
my second point is that assessment of risk canal
utilizing your basic boss boring
can actually direct your management about as
or if high risk you do ctpa
um if pe or you do compression
ultrasography
and third is anticoagulation as a core of treatment
we should know when to anticoagulate not LGBT
um should be given anticoagulation
so
it was mentioned in the lectures that we anticoagulate
proximal DVT and what is proximal DVT
from pocket yell pop
no um
as well as this LGBT with risk for extension
as well as increased risk factors
and when we enter to ogulate
you also have to focus not only on the intensive face
but also we have to think about the primary treatment
the extended treatment as well as secondary prevention
you've mentions of your deck side Adrian
which is quite a good addition to the wax
another option for secondary prevention for occurrence
and the fourth point I would like to all series is um
the treatment should be highly individualized you know
we should be able to discuss
this treatment options to our patients
we have to consider the cost
you know um the location of the trombles
are patients comorbidities
uh fully pharmacy special debeding risk
social bleeding risk we can use
um has bladder input
bte bleed
to assess them regularly on their risk
so that we can antiquagulate them completely
um note that when we antiquagulate DVT or vte
it's usually not the minimum of
the minimum of these three months
so we really have to hide
individualize
and discuss this treatment options with our patients
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