Natural History of Upper and Lower DVT - SD

Introduction

My name is Dr. Mark Oliver.

I am co-director of the Vascular Laboratory at Morristown Memorial Hospital in Morristown, New Jersey, and an attending physician there.

I am also clinical assistant professor at the Sinai School of Medicine in Mount Sinai, New York.

My talk today will be on the natural course of lower and upper extremity DVT, the natural history of lower extremity DVT.

Disclosure and Prevalence of VTE

The disclosure here is that I was a past speaker of Sanofi Aventis.

The prevalence of VTE is recognized in about 260,000 patients a year in the United States, less than 50% of the VTE are symptomatic.

The total DVTs have been thought to be over 500,000, but in reality, they're greater than 2.5 million.

As you can see, the annual incidence of fatal pulmonary embolism of interest, it hasn't changed over the years. It's about 200,000.

About half are incurable, but the other half are potentially curable.

And as you can see, 80% of these lives could be saved if we use effective prophylaxis.

What's important to note is the morbidity potential morbidity after acute DVT as Poni has shown here that the post thrombotic syndrome is up to 30% of patients eight years after the initial event.

Anatomy of the Deep Venous Systems

This is just an overview just showing you the lower extremity deep venous system to be aware of the superficial system and the deep system that occurs.

What's important is to appreciate that the fem pop area is considered the major area, the iliofemoral region. Consider minor area of DVT and we will show you the differences in the natural course of disease with these areas.

This is an area of the upper extremity DVT to be aware of the anatomy again, without going into great detail, the significance of the deep systems and also of the superficial systems in the upper extremity.

Pathophysiology of Clot Formation

In addition to the macroscopic anatomy, we also have microscopic anatomy.

There's a constant tug of war that goes on in our bodies in which we form clot and we lyse clot.

We have clotting factors you can see that end up with forming a fibrin mesh.

And the end result is that that fibrin mesh combines with platelets that clump together to form a clot.

It turns out that on the arterial side of things, these are platelet-rich thrombi, whereas the thrombi on the venous side are platelet poor.

The end result is that aspirin certainly works better on the arterial side because it's an anti-platelet drug.

This tug of war goes on continuously in our body, and as you can see, we have a buildup of the clot and then we have a lytic cascade to break down the clot.

When there is an injury to the lining in the vessel wall, this induces clotting and thus trauma can induce clotting.

In addition to that, when there's stagnation, clotting factors hang around long in our body and therefore there's a high risk of clotting.

So this is responsible for our understanding of some of the pathogenesis of having a DVT.

Natural History of DVT

Here we see clots. What about the natural history of DVT?

Spontaneously you might see a lytic situation or lysing we can propagate or embolize we catalyze over time or permanently occlude the vein.

This is a wonderful article that I referred to by Thomas McAllister, et al.

Using venography at that time was the gold standard in 1971, and it shows us that you see here in a the loose clots B then becoming adherent C adhering D occluding with collateral, and finally e with recanalization in ZY Bell's book, he shows how this would look to us on the natural course on venous imaging.

As you can see in the left upper area there you see a clot where there's dilatation.

We may also have a spongy feel to this clot, which suggests that this is more of an acute clot over time.

There's retraction in the clot.

As you can see here, the diameter and the vein is equal to the diameter in the artery would suggest an indeterminate age, but maybe some clot that is older.

As we get further on, we can see collateralization and we can see further down here evidence of an older clot, which is retracting the small, which is very hyperechoic.

Diagnosis of Recurrent DVT

Poni has come up with an article of interest for recurrence, which is very hard to diagnose In the past, compression ultrasound was really the only way we could diagnose using that criteria.

But what he has done is add on. He has added on the thrombus thickness greater than two millimeters, so that if you develop a thrombus thickness greater than two millimeters from previous studies, that there's a hundred percent sensitivity and specificity he determined for determining recurrent DVT.

This is an example now of a recurrent DVT.

Notice that you'll see this bright echogenic area here, which we had previous to this examination, and then the patient developed a newer clot formed on top of the bright echogenic area, which was consistent with a recurrent DVT.

Natural History of Acute DVT

What about the natural history of acute DVT?

It turns out, as we pointed out before, up to one third of patients with acute DVT will never progress to post thrombotic syndrome.

It appears that lysis of the venous thrombi appear to begin very early in the course of DVT, as we can see here, you can see that less than 30 days out, almost half of the patients show some lysis of their DVT.

The percentage of venous segments that remain occluded was less than 20% at a mean follow-up, which we'll so on the next graph and is clear that more rapidly venous lysis occurs, the more likely it is for valve function to be preserved, which I will show you on the proceeding slides.

Here's an example here showing you that less than 80% of residual occlusion when you get out to 270 days, and also a very interesting slide, which shows you that if you have it takes less time to have lysis of a clot, you will have less venous insufficiency and less reflux such as you see here in let's say the common femoral vein, a major vein.

You can see here when there's a great lytic time, there's more time that we have a high risk of getting a reflux of interest if we go to the calf veins, we'll notice here, like in the posterior tibial vein, that there really was no difference with the lysis time as far as developing reflux or not.

And this is some of the reasoning behind in a major DVT why we might use thrombolytic therapy, whereas it might not be as efficacious in the calf DVT.

This is an example from the past. Its EMS literature and radiology of showing you lysis 72% being complete.

As you can see here with complete resolution and relief of leg pain edema, about 85% of the patients.

Role of Anticoagulation in Natural History

This is an article for vascular medicine showing the stability during acute phase of therapy.

And what's very interesting, we always talk about adequate anticoagulation and this shows you how important this is in a natural course of disease.

As you can see here, if greater than 80% of the time we have adequate anticoagulation, we have a very low risk of recurrent DVT significantly lower than if our anticoagulation is not adequate.

80% of the time or less than 80% of the time, you'll see a much higher rate of recurrence in our natural course of DVT.

Interestingly enough, in this article, it showed us that there were frequencies of contiguous and non-contiguous extension of venous thrombosis during the first weeks three weeks of therapy, and this was higher than was reported.

The majority of these occurrences were patients that were asymptomatic and the risk of developing this complication was inversely associated with the level of anticoagulation achieved.

As we pointed out on the previous slide, The development of venous valvular reflux is significantly more common among extremities with recurrence regardless of what the recurrent event is associated with new symptoms.

Risk Factors for Recurrent DVT

What about other components of the natural history of VTE?

Karen, in 2003 in circulation, has shown us that there are certain factors that may appear to be risk factors for recurrent DVT, and this is at times so much controversial recently, but things such as antiphospholipid antibodies, elevated homocysteine levels, homozygote factor five, levels of factor eight, probably deficiencies of antithrombin three, protein C and protein S, these all appear to be higher risk factors For recurrent DVT.

Management Insights from Natural History

I use a lot of this material that I'm showing you today in the way I help to manage patients with DVT, and this is an extremely important slide in point.

Right now, the highest risk period for fatal post-op PE appears to be about three to seven days following surgery Without treatment.

About one half of patients with symptomatic proximal DVT or PE are expected to have recurrent thrombosis within three months.

And what's also very important with this proximal DVT component or this major DVT component of fem pop DVT, we know in the literature that if you do not treat 50% of those patients, we know that if you do not treat these patients at all, 50% of them will develop PE a very significant number.

We also know that about a quarter of untreated symptomatic calf DVT will extend into the proximal veins, and most of these extensions of interest, which has been shown in the literature, will occur within a week or two of presentation.

So in other words, if you get out to a week or two after the patient presents with calf DVT, the likelihood is gonna be very low that this will propagate.

And this becomes very important when you're dealing with patients for which you cannot use anticoagulation, have a higher bleeding risk, and they have a calf DVT, you can potentially do serial scans on those patients so that after 10 to 14 days, you know you'll be in better shape that they're not gonna propagate their DVT.

Another factor is Poni as far as the natural course of disease is evidence of residual venous thrombosis as a predictive factor of recurrent venous thromboembolic disease.

The conclusion in this paper was that residual venous thrombosis is an important risk factor for recurrent DVT, and it turns out if you're dealing with a residual lesion that's greater than three to four millimeters at the time you wanna stop your anticoagulation has been shown as per this paper, you'll have a higher risk of recurrent DVT.

And that is why when I have a patient that I'm ready to take off anticoagulation at three to six months that I will scan that patient.

If I find a clot that's four millimeters or more, I will actually keep them on anticoagulation for another month or two until that clot decreases with its residual volume and diameter.

And this hopefully decrease my risk of DVT when I take them off the anticoagulant and then after I take them off the anticoagulant, I measure them and look at their legs a month later.

What's interesting is that we have been able to also use D dimer levels in the literature.

D dimer is an end product of fibrin and to determine the risk of recurrent venous thromboembolic disease.

In this particular paper, as you can see, it was shown that patients with the first spontaneous VTE with a D dimer level that was normal at this level after we would take them off their anticoagulation, they have a low risk of VTE.

What is also now shown in the literature that if you stop the patient with anticoagulation and a month later measure their D dimer, and if it's normal, they have a much lower risk of having recurrent DVT of interest was a recent article in anology, in April I believe, which showed that the volume of the clot really correlated very nicely to the D dimer level in the prevent trial, which you can see in 2003 is certainly not impressed any longer.

I was a principal investigator this trial, this was at Morristown and what it showed us that is that you could use long-term low intensity warfarin being highly effective and safe to prevent recurrent DVT.

In other words, if you had a patient that was on six months of conventional warfarin therapy with an INR of two to three, and then you lower the INR between 1.5 to two in this particular paper, we decrease the risk of recurrent DVT by 60%.

This is unlike patients with atrial fibrillation for which we want to maintain the INR between two and three.

And as many as you know, there is now a drug that is out that may replace or is replacing Coumadin Select the patients with AFib.

We do not have to cover look at the INR at all, and this will occur of course in the future with managing patients with DVT, but this makes it easy though for patients that are on warfarin long-term therapy to follow 'em, keeping the INR between 1.5 to two so that we only need the INRs between every one to two months.

Management of Lower Extremity DVT

The management of lower extremity DVT is as we well know, interestingly enough, for over 40 years we've been using anticoagulation with conventional heparin and warfarin.

Now we use different types of heparin such as LMWH and also of course LMWH like Lovenox.

And we talked about the future of not only using warfarin now, but the future of other drugs that may replace warfarin.

In addition to that, we talked about the appropriateness of using thrombolytic agents, especially in patients with massive iliofemoral DVT also gradient elastic stockings are utilized and the way they work, which is very interesting jokes was an engineer.

He had horrible varicose veins. He stood up in a swimming pool and he felt better.

And as you well know, standing up with varicose veins is not a great idea for long periods of time.

It turns out that he discovered that the reason he felt better in the swimming pool was because the hydrostatic pressure, the water pressure of the bottom of the pool was greater than the water pressure in the top of the pool in a gradient fashion.

And as a result, this gradient was able to allow us to increase blood flow through the leg, also utilizing intravascular filters and also thrombectomy as other modalities of management of lower extremity DVT.

Upper Extremity DVT

In selected instances, the upper extremity DVT is a little bit of a different animal because these type of patients, whereas most common DVTs are more likely to occur in the lower extremity.

We also then know that 90% of all pulmonary emboli will come from lower extremity DVT, but in the upper extremity DVT, we usually get the DVT for other reasons.

Very commonly with central venous catheters with pacemakers, IV drug abusers, there's an entity called effort thrombosis for which athletes such as rowers, et cetera, weightlifters, develop an anatomic issue of compression on the vein, and they develop effort thrombosis in the upper extremity DVT.

We also, if there's a spontaneous upper extremity DVT, we have to suspect that there may be a malignancy or some form of a hypercoagulable state that occurs in these situations.

Thoracic outlet syndrome, the axillary subclavian thrombosis, we know in these patients what's unique is that there's a 25 to 75% chronic disability and persistent symptoms with no treatment or treatment with anticoagulation alone.

Treatment Guidelines for Upper Extremity DVT

The current treatment guidelines in chest supplement, this is June, 2008, will be coming out probably in the spring of 2012.

This occurs every three to four years, and we notice here that our initial anticoagulation of acute DVT the upper extremity is really the same, is very similar as it is for the lower extremity.

However, in selected patients, we may elect to use catheter directed thrombolytic therapy as our initial treatment.

These are patients of course that have a low bleeding risk, severe acute symptoms and especially if expertise and the appropriate resources are available for these patients.

These guidelines were different previous guidelines because they're suggesting to utilize catheter directed thrombolytic therapy rather than systemic thrombolytic therapy.

Now, on this busy slide, you can see that the new modalities of potentiality of treatments that we can use in an upper extremity that's unique to upper extremity DVT.

You notice here catheter extraction, surgical thrombectomy, transluminal angioplasty, stent replacement, staged approach of lysis, followed by intervention or surgical approach for the initial treatment of upper extremity DVT.

As you can see, these are done in selected patients with upper extremity DVT, with patients that have failure to anticoagulant therapy or thrombolytic therapy with persistent symptoms, again, in selective patients.

If there is a contraindication for this despite adequate therapy, then these patients we have to consider using the placement of a superior vena cava filter as a suggested treatment catheter extraction.

As you can see, the most recent guidelines are essentially the same in the past, except newer techniques as I pointed out, such as angioplasty stents, stage lysis, are now modalities that we use, which we did not use in the past.

Conclusion

In conclusion, the natural course of DVT is based on clinical and lab testing, including lysis, extension, recanalization, and possible recurrence.

The knowledge of the natural course of lower and upper extremity DVT will aid in the appropriate management of these conditions and is something that we can use every day to appropriately take care of these particular patients.

Thank you very much.