Venous Thromboembolism

Summary

This 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

• 😀 Early diagnosis is crucial in managing Venous Thromboembolism (VTE) due to its life-threatening complications, including high risks of death and recurrence.
• 🔍 Identification of symptoms and risk factors for Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) is essential for prompt treatment.
• 🩺 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.
• 💊 Anticoagulation is the primary treatment for VTE, with decisions on its duration and intensity based on the patient's condition and risk of bleeding.
• ⏳ The duration of anticoagulation therapy is a critical decision, with guidelines suggesting indefinite continuation based on patient risk factors.
• 💡 The risk of recurrent VTE remains significant even after the cessation of anticoagulation, necessitating ongoing evaluation and management.
• 🛑 The natural history of VTE often involves recurrence, highlighting the importance of secondary prevention strategies.
• 💊 Suludexide is a novel drug studied for the prevention of unprovoked recurrent VTE, offering a different mechanism of action compared to traditional anticoagulants.
• 🧬 Suludexide's unique affinity for the endothelium and its role in restoring damaged endothelium make it a promising option for secondary prevention.
• 🌐 The SURVEY trial demonstrated the efficacy of suludexide in reducing the recurrence of unprovoked DVT without major bleeding episodes.
• 📝 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

00:00

🩹 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.

05:02

🛑 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.

10:03

📋 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.

Keywords

💡VTE

VTE stands for Venous Thromboembolism, which is a condition that includes two related disorders: deep vein thrombosis (DVT) and pulmonary embolism (PE). In the video, VTE is the main theme as it discusses its management and treatment, emphasizing the importance of anticoagulation therapy to prevent recurrence.

💡Anticoagulation

Anticoagulation refers to the use of medications that make the blood less likely to clot, which is a critical aspect of VTE treatment. The script discusses the decision-making process around anticoagulation, including the potential for indefinite duration based on patient cases, and the risks and benefits involved.

💡Recurrence

Recurrence in the context of VTE refers to the re-occurrence of blood clots after the initial treatment. The script highlights the significant risk of recurrence, which can be as high as 40%, and the role of continued anticoagulation in managing this risk.

💡Fibrinolysis

Fibrinolysis is the physiological process of dissolving blood clots by the body's own enzymes. The script mentions that the body heals itself through fibrinolysis and absorption, but not all blood clots are reabsorbed, leading to the potential for recurrence of thrombosis.

💡DVT

DVT, or deep vein thrombosis, is a specific type of VTE where a blood clot forms in a deep vein, usually in the legs. The script uses DVT as an example to illustrate the process of clot formation and the challenges of treatment and prevention.

💡Reassess

Reassessing a patient's condition is a key part of managing VTE. The script suggests that guidelines recommend reevaluating a patient's risk factors and treatment plan every three months, which is crucial for determining the continuation or cessation of anticoagulation.

💡Sulodexide

Sulodexide is a medication mentioned in the script as a potential treatment for preventing the recurrence of unprovoked VTE. Unlike traditional anticoagulants, sulodexide works by binding to antithrombin III and heparin cofactor, which inhibits thrombin generation, offering a milder approach to treatment.

💡Glycoproteins

Glycoproteins are proteins that have carbohydrate groups attached. In the script, sulodexide is described as having glycoprotein components that are similar to those found in the glycocalix, which is important for its unique affinity to the endothelium and its restorative effects.

💡Endothelium

The endothelium is the thin layer of cells that line the interior surface of blood vessels. The script discusses the importance of maintaining the integrity of the endothelium for optimal VTE management, with sulodexide being highlighted as a medication that can help restore damaged endothelium.

💡Risk Factors

Risk factors are characteristics or conditions that increase the likelihood of a disease or condition. In the context of the video, risk factors are discussed in relation to VTE, and they play a role in determining the duration and type of treatment, including the decision to continue anticoagulation.

💡Individualized Treatment

Individualized treatment refers to tailoring medical care to the specific needs and circumstances of each patient. The script emphasizes the importance of considering individual factors such as cost, location of the thrombus, comorbidities, and bleeding risk when deciding on the duration and type of VTE 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