vascular medicine

Thrombolysis for Acute DVT Management


In this podcast, Brian G. DeRubertis, MD, answers our questions about his session at the 2021 VEITHsymposium, which highlighted 2 large clinical trials on the more-aggressive strategies of thrombus removal for patients with deep vein thrombosis.

Additional resource:

Brian DeRubertis, MD, is the chief of Vascular & Endovascular Surgery at Weill Cornell Medical Center in New York, NY.



Amanda Balbi: Hello, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator Amanda Balbi with Consultant360.

To continue our coverage of the 2021 VEITH Symposium, we are speaking with Brian DeRubertis, MD, who is the chief of Vascular & Endovascular Surgery at Weill Cornell Medical Center in New York, NY. He recently presented “Thrombolysis for Acute DVT: Utilization and Guidance From Current Clinical Trials,” and joins us today to talk about the take-home messages.

Let’s listen in.

Can you give us a brief overview of your session or the research you’re presenting?

Brian DeRubertis: Sure, so the session is quite an interesting session. There's a variety of topics; they all have to do with thromboembolic disease or venous thrombosis. Most of the session is focused on DVT management (deep vein thrombosis management) and how we approach this problem, as well as some changes that have occurred over time and the way we manage this problem.

By that, I am referring specifically to the progression from simply anticoagulating patients alone with anticoagulation to moving into more-aggressive strategies of thrombus removal. Previously this included primarily thrombolysis, catheter-directed thrombolysis, and that's largely what my talk covered. 

In addition to that, the session will also include discussion of various single-session mechanisms by which we clear thrombosis more aggressively. By that I mean not just catheter-directed thrombolysis but also some of the newer devices that we have for clot retrieval—thrombectomy devices of various types.

So, it’s a broad session that covers really the evolution of management, as well as some of the data behind some of these specific types of management.

Amanda Balbi: Can you talk a little bit about the newer methods or the approaches to clot removal?

Brian DeRubertis: Sure. Historically, as I mentioned before, anticoagulation was the gold standard, and anticoagulation is still a reasonable choice for many patients depending on their presentation, where their DVT is, which part of the venous system it is, whether it's lower leg vs femoral vein or iliocaval. Each of these different areas have implications for different potential types of treatment.

Anticoagulation alone was gold standard for some patients. As we move to more-aggressive treatment, catheter-directed thrombolysis is the next escalation. That's essentially where we try to embed a catheter directly into the area that has occluded or where the DVT exists, and then drip TPA—that’s the primary drug we use these days—TPA or tissue plasminogen activator. Drip that over multiple hours, even sometimes several days, to try to dissolve the clot.

That has the benefit of using lytic therapy that slowly dissolves a clot over time really can help dissolve clot behind venous valves, and it's been a tried-and-true way of managing this problem. The downside of that, of course, is that you have inpatient monitoring of the patient undergoing this therapy over many hours or, again, even up to several days.

There's a bleeding risk that comes with using TPA, especially for prolonged periods of time, and that's why, for both hospital resource utilization as well as various risks attended to using TPA, we've started exploring using other devices such as mechanical thrombectomy devices. There are a number out there.

Experimenting with these different types of catheters to try to do single-session thrombectomy rather than focusing more on the thrombolysis part of it.

Amanda Balbi: Interesting. And then, at what point during the treatment regimen does anticoagulation management stop working, and therefore, either the primary care provider or the cardiologist have to refer to surgery?

Brian DeRubertis: Yeah, that's a great question. That's largely the focus of my talk, as well. Anticoagulation is the immediate first-line treatment for any diagnosed DVT. So, if you have a patient who comes into the emergency room or the primary care doctor’s office and has a swollen leg, is suspected of having a DVT—our first step in diagnosis is to perform a duplex ultrasound to confirm or refute the diagnosis of the DVT.

Once DVT has been diagnosed, immediate anticoagulation is the first step at that point, and now we have various oral options, as well as lovenox, low-molecular-weight heparins, in addition to warfarin, which is what we historically we've always used. Now we have a lot of good options for anticoagulation.

But I would say, to answer your question when is it time to refer on to a vascular specialist, I think that the time is immediately upon diagnosis. One of the points that I made in my presentation during this session is that not all patients are necessarily appropriate patients to undergo these aggressive strategies of thrombus removal. There's a lot of debate about which patients should be treated with aggressive strategies of thrombus removal and what is the long-term benefit of that. That's part of what I got into in my presentation.

Not every patient qualifies or is really going to be expected to benefit from these more-aggressive strategies. We don't ever want to have a patient, who has been evaluated and should have had that discussion and had that offered to them, not get offered that treatment during the window in which that treatment is applicable. 

Because, of course, after you've had a DVT for a couple of weeks or certainly a few months, some of these thrombus removal strategies no longer work. Thrombolysis is no longer an option. I've met a number of patients in my career who have had extensive ileofemoral DVTs, or sometimes just femoral DVTs that are extremely symptomatic, and those patients, for whatever reason, haven't been offered lytic therapy or other thrombus removal strategies.

Until 3 or 4 months go by, they remained highly symptomatic, and at that point they get referred to me with really very few options that can treat them. So, what we're trying to do is get the message out that all patients who have been diagnosed with a DVT should immediately see a vascular specialist within the first week of their diagnosis.

What I typically do is I will see the patient in my office within days of the diagnosis, and I rush to get them in to see me. For some patients who are mild to moderately symptomatic, I just continue their anticoagulation that’s already been started. I generally will see them back in about a week and see if they've had full resolution of their symptoms. Those who do see resolution, I often do nothing further but watch them with anticoagulation, but those who remain highly symptomatic after a week, we tend to suggest for those patients that we get them in to be in the CATH lab or in the OR to get to one of these strategies of aggressive thrombus removal.

There is some guidance from clinical trials and that's another topic of discussion in my presentation. There's been 2 large national randomized trials that have looked at using some type of thrombus removal strategy. The CaVenT trial in Norway was about a 200-patient trial, which did show an improvement in ileofemoral patency for those patients who underwent aggressive strategy of thrombus removal. They also showed, both at 2 years and 5 years, lower rates of post-thrombotic syndrome, so that was a positive trial for use of these more-aggressive strategies.

The ATTRACT trial was an NIH-funded trial in the United States that randomized patients to anticoagulation vs and more-aggressive strategy of thrombus removal. A difference from the CaVenT trial, in terms of its primary endpoint of any post-thrombotic syndrome, they did not show the difference between the two.

But that said, if you look at the subsets of patients with more proximal illiac vein thrombosis compared to infrainguinal thrombosis, those patients with more proximal thrombosis work much more likely to see a benefit, at least numerically in terms of the reduction of post-thrombotic syndrome. Those patients with moderate or severe post-thrombotic syndrome were more likely to have a benefit from the more-aggressive strategy. So, even though the primary endpoint of any post-thrombotic syndrome was no different between the 2 arms, if you look the more moderate-severe patients they certainly did benefit.

The results can be a little bit confusing or a little mixed, I would say. And I think that in the primary care world or in the general medicine world, they may look at the headlines of some of these trials and think that maybe there's no benefit to a certain type of therapy, but you really have to understand the subsets of those patients and use that data to make somewhat of an educated decision based on your specific patient.

That's why, as I mentioned moments ago, I'll see a patient initially in the office, if they are moderately symptomatic, I’ll watch them for a week. Also, I take into account, where their thrombus is. If it's an iliocaval thrombus, then I'm much more likely to offer them thrombolysis or a pharmacomechanical thrombectomy. If it's more of a popliteal DVT, I’m a little less aggressive about those.

Amanda Balbi: Great. So, with all of these take-home messages, I think you mentioned a few in there, how can clinicians implement those into daily practice tomorrow?

Brian DeRubertis: I think the biggest message I would say for the nonvascular specialist is to have a high suspicion of DVT. For those patients presenting with the obvious signs and symptoms, get them immediately started anticoagulation.

And really plug them into a vascular specialist of some type—someone who's very familiar with the full range of more-aggressive therapies of thrombus removal like a vascular surgeon, an interventional cardiologist, or radiologist—someone who really has that venous disease, deep venous disease as part of the full spectrum of care that they offer patients. That's step number one.

Then I think for those vascular specialists who are practicing and trying to decide how to choose the right patients for the right interventional therapy, this session overall does a great job of introducing them to some of the devices that are available for these patients. 

In terms of making that decision as to whom to intervene, I think the clinical trials that I highlighted give some guidance, but I'd say that the most important thing is to take the learnings from those trials and take it to that individual patient and have an open dialogue and open line of communication with the patient to see if they are improving with anticoagulation alone. And if they're not, have a low threshold to get them in to a CATH lab and start an intervention within, ideally, 7 days but really no more than 2 weeks, because that's the window at which this type of therapy is most effective.

Amanda Balbi: That’s interesting. So, what is the next step in the research for DVT management and approaches?

Brian DeRubertis: That's a good question and I say that primarily because there have been several large, randomized trials that have tried to tease this question out in terms of which patients are most likely going to benefit from these different types of therapy. I don't know that we'll ever have that kind of large, randomized trial in this area that has been successfully carried out. Again, I think each of these trials suffered from prolonged recruitment periods of their patients, and these are big endeavors and they're fairly well done.

And each has their limitations and some criticisms. For example, in the ATTRACT trial, the use of the primary endpoint of having any post-thrombotic syndrome I would say obscured what the ultimate conclusions could be from this trial, because those are a somewhat heterogeneous group of patients. But that was largely necessary for recruitment of patients, and so I don't know that we'll have any better large-scale, randomized controlled trial data than these 2 trials. I think these 2 trials do give us a fair amount of information.

Going forward, I think the next step is the recognition that catheter-directed thrombolysis, where we're administering TPA over many days, is not ideal. I think that the future research will most likely focus on those new devices that are available that are able to remove a large burden of thrombosis in a very short period of time for single-session lytics. 

I think that the future research that is probably most relevant to our patients will be the research that shows how effective those devices are on an individual patient-by-patient basis.

Amanda Balbi: Interesting. Thank you so much for joining me and answering all my questions.

Brian DeRubertis: Great, my pleasure.