Expert Conversations: VTE and COVID-19 Infection
In this podcast, Shari Barnett Brosnahan, MD, and Bhavin Dalal, MD, talk about venous thromboembolism (VTE) and COVID-19 infection, including the treatment options, clinical challenges, and updates in trials. They also presented on this topic at CHEST 2021 Annual Meeting.
- Rivera-Lebron BN, Brosnahan S, Rali P, Dalal BD. COVID and VTE: clinical challenges and update in trials. Talk presented at: CHEST 2021 Annual Meeting. October 17-20, 2021; Virtual. https://chestmeeting.chestnet.org/session/covid-and-vte-clinical-challenges-and-update-in-trials/
- Lemos ACB, do Espírito Santo DA, Salvetti MC, et al. Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID). Thromb Res. 2020;196:359-366. https://doi.org/10.1016/j.thromres.2020.09.026
- Sadeghipour P, Talasaz AH, Rashidi F, et al; INSPIRATION Investigators. Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: The INSPIRATION randomized clinical trial. JAMA. 2021;325(16):1620-1630. https://doi.org/10.1001/jama.2021.4152
- Lopes RD, de Barros E Silva PGM, Furtado RHM, et al; ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397(10291):2253-2263. https://doi.org/10.1016/s0140-6736(21)01203-4
- Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial. J Thromb Haemost. 2021;19(9):2225-2234. https://doi.org/10.1111/jth.15450
- Lawler PR, Goligher EC, Berger JS, et al; ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators.Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med. 2021;385(9):790-802. https://doi.org/10.1056/nejmoa2105911
- Goligher EC, Bradbury CA, McVerry BJ, et al; REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med. 2021;385(9):777-789. https://doi.org/10.1056/nejmoa2103417
- Sholzberg M, Tang GH, Rahhal H, et al; RAPID trial investigators. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ. 2021;375:n2400. https://doi.org/10.1136/bmj.n2400
- Spyropoulos AC, Goldin M, Giannis D, et al; HEP-COVID Investigators. Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in hIgh-risk hospitalized patients with COVID-19: The HEP-COVID randomized clinical trial. JAMA Intern Med. 2021:e216203. https://doi.org/10.1001/jamainternmed.2021.6203
Shari Barnett Brosnahan, MD, is a pulmonary critical care attending and an associate program director for the critical care fellowship at New York University Langone Health in New York, New York.
Bhavin Dalal, MD, is an associate professor at Oakland University William Beaumont School of Medicine, a pulmonary critical care sleep medicine physician at Beaumont Health, and a program director of the pulmonary critical care fellowship at Beaumont Health in Canton, Michigan.
Stephanie Holland: Hello everyone and welcome to another installment of "Podcast360," your go‑to resource for medical news and clinical updates. I'm your host, Stephanie Holland, alongside our moderator, Jessica Bard, with Consultant360.
Today we're speaking with Dr Shari Brosnahan and Bhavin Dalal, who recently presented the recent study on clinical questions surrounding VTE and COVID‑19 infection at Chest2021. To begin, could you give us a brief overview of your background and experience?
Dr Shari Brosnahan: My name is Shari Brosnahan. I'm one of the pulmonary critical care attendings at NYU Langone Health in New York, New York. I'm also one of the associate program directors and the pulmonary critical care fellowship there.
Dr Bhavin Dalal: Good afternoon, everyone. My name is Bhavin Dalal. I'm an associate professor at Oakland University William Beaumont School of Medicine and a pulmonary critical care sleep medicine physician at Beaumont Health. I'm a program director for the pulmonary critical care fellowship for the Beaumont Health, Detroit area, Michigan.
Jessica Bard: Thank you both for joining us on the podcast today. We appreciate it. Can you please start by giving us a brief overview of your session in your research please?
Dr Brosnahan: Our section was great. We were able to cover all the clinical questions surrounding VTE and COVID‑19 infection. We walked through different aspects of COVID‑19, and the pathophysiology behind thrombosis as well as treatment options in the wards and the ICU.
Dr Dalal: We had a session about, which are the patients good for the screening of the VTE or a DVT, or pulmonary embolism? Which are the patients good for therapeutic and prophylactic anti‑coagulation? What can we do about VTE in general with the COVID‑19 infection?
Jessica: I know there's a lot to get into. If you could just take the key clinical takeaways, what would you say are the key take‑home messages for the audience?
Dr Brosnahan: I think COVID‑19 has been very interesting for a lot of people because we've shifted so quickly in a lot of our treatment paradigms. Initially, we kept on seeing patients come in, we were overwhelmed by the amount of thrombosis we are seeing.
It made us think that these patients were pro‑coagulopathic and were more likely to clot. However, there are a lot of randomized control trials, that have been done recently, that show that this is more of a confusing question than we thought originally.
If we look at the randomized control trials, what they've shown is that in floor level patients, patients who don't require high‑flow oxygen, that these patients benefit from anti‑coagulation. However, in the ICU patients, there was no benefit seen in anti‑coagulation.
In fact, maybe even a trend to harm. I think this is even more confusing because when we look at the patients who are more likely to have blood clots, that's higher in the patients that are in the ICU and lower in the patients that are in the floor level.
The question is, what are we protecting against, and how is this helpful for patients? It's still yet to be discovered.
Dr Dalal: Another important key message for the COVID in general I will say is whatever we are going to discuss today may not be truthful tomorrow. It's an ever‑changing scientific field, and just in the last 18 months, we have seen A‑to‑Z and Z‑to‑A for every single diagnostic and treatment intervention we have thought about COVID.
You might have to record the session again next month.
Jessica: I think that's a good tee‑off for the next question. I know information is changing all the time. What's next for COVID‑19 and VTE research?
Dr Brosnahan: It's getting more into this mechanistic idea of what's causing anti‑coagulation to be beneficial in a patient population, that might be less a risk for venous thrombosis. The question, is heparin...Even more of a confusing question surrounding this is if heparin, or anti‑coagulation, is what's causing this benefits to be seen.
There are trials and we'll have a platform trial that was published in the "New England Journal," that shows that heparins portend favorable prognosis on floor‑level patients. We saw in COVID that Lovenox also shows this favorable prognosis.
However, in the LOPED study, we don't see a trend towards paper prognosis with the use of DOAC, to let the Xa inhibitors. The idea is that heparin, not just simply anti‑coagulation, might be part of this treatment phenomenon.
It has the ability to interact with the spike protein, and the spike protein is important for getting into cells, via the ACE‑2 receptor. Whether heparin changes the way the spike protein interacts with the ACE‑2 receptor is still under investigation.
What's next is that further differentiate heparin from other anti‑coagulation. Then what kind of thrombosis are we talking about? Because conventionally, when we look at anti‑coagulation of VT, we're talking about venous thrombosis and pulmonary embolism.
However, when we look at COVID specifically, we see arterial thrombosis in a reasonable number of patients. When we look at the hep COVID study, we look at VTE specifically. There can be differences than if we look at, include arterial thrombosis, and take endpoints such as organ free survival days, or mortality, which have been shown to be improved with heparin products.
Dr Dalal: Just to kind of elaborate on the Shari's idea. As she mentioned, the heparin may have additional anti‑viral, anti‑inflammatory, and even some other activities, which we are not aware of, apart from the anti‑coagulation effects.
That's why the heparin was shown to improve mortality of the organ free‑support days, in the multi‑platform randomized control trial, in the non‑sick or non‑critically ill patients. They were not shown the same improvement in the critically ill patient, what we originally believed all of us do a lot of anti‑coagulation or therapeutic anti‑coagulation for our ICU or the sickest of the sickest population.
The evidence of the study results were completely counterintuitive. One of the thought process behind that is that during the early phase of thrombosis, the clots are fresh. If you give anti‑coagulation during that time, they are more likely to work.
When the time goes on, and the clot becomes more organized, anti‑coagulation or therapeutic anti‑coagulation maybe even harm. These are very recent findings from the New England Journal of Medicine article published in August of 2021. Still not adopted widely from the practice standpoint, and there are a lot of questions emerged after the study visits.
Jessica: Is there anything else that you'd like to add on this topic that you think that we missed?
Dr Brosnahan: When I talk about all these randomized control trials, we think about randomized control trials as the gold standard and infallible. All of these randomized control trials are all open‑label, which makes the endpoint, being mortality, probably the best endpoints we could pick or organ-free survival.
If we're looking for thrombosis generation, that can be harder to look for in a non‑blinded study because a provider might think the pretest probability of a patient having a thrombosis, if a patient is getting anti‑coagulation, is significantly different.
Furthermore, they might think undergoing an invasive test or a non‑invasive test, such as an ultrasound, might not be worth it, because patients aren't getting the treatment for that disease. A lot has been made about the endpoint seen in the studies, including not being related to thrombosis.
I would remind everyone that this being open‑label make that harder to achieve.
Dr Dalal: The one other point I would like to add, is the value of a D‑dimer. In the COVID, VTE, we have given a lot of value, the value of the D‑dimer. This study results, especially in non‑critically ill patients, or floor patients, what Shari was saying earlier, those who got a benefit from therapeutic anti‑coagulation, irrespective of a D‑dimer value.
They had done analysis for the people who have a low D‑dimer, which was defined as less than two times upper limit of normal, roughly speaking at 1,000 units, versus the high D‑dimer and unknown D‑dimer. In all 3 groups, they have seen a significant survival or the organ free‑support days benefit. What is the value of a D‑dimer now? It's, again, another confusing question.
Jessica: Thank you both for your time today. I appreciate it. It was a pleasure speaking with you both.
Dr Brosnahan: Thank you so much for having us.
Dr Dalal: Thank you.
Stephanie: Catch up with all of our episodes at consultant360.com/podcasts. Stay tuned for more.