Decoding the VTE enigma: Learnings from COVID 19. Episode 3 - Dr. Abhay Bhave and Prof. Roopen Arya

This edition of the podcast will focus upon:

  • Extending thromboprophylaxis for patients with COVID-19 beyond hospital discharge
  • Resolving concerns around:
  1. Vaccine-induced thrombotic thrombocytopenia (VITT)
  2. Anticoagulation use before COVID- 19 vaccination

Time stamp



00:07  - 00:47

Male Speaker

Welcome to VTE Unplugged, a brand new podcast series curated by Sanofi. The aim of VTE Unplugged is to bring latest in the field of Venous Thromboembolism management delivered by renowned experts in this field. Today, let's listen to our ongoing discussion on decoding the VTE enigma learnings from COVID-19 . In the previous episode, we exchanged information on VTE management in special cohort of patients like renally impaired, obese, pregnant women, and also among cancer patients. Importance of biomarkers like D-dimers were also alluded to in detail by Prof. Roopen Arya. Now, we will take this discussion forward.

00:52  - 01:38

Dr. Abhay Bhave

So many of our clinicians find comfort in extending the VTE prophylaxis that was given to the patient in the hospital beyond discharge, and this will be the thought process that the inflammatory process might still go on when they're at home, and they might experience thrombotic events at home. So to prevent it, they would like to extend. Now this is not the usual practice for our patients of medically ill who are in the hospital. When we send them home usually based on the scoring, we would not have sent everyone home on some prophylaxis. But in your opinion, is there any kind of scientific evidence to confidently recommend extending prophylaxis in patients with COVID-19 when they are going home?

01:40  - 04:27

Prof. Roopen Arya

Thanks for that question, which is a very important one because I'm aware that the use of extended thromboprophylaxis after hospitalization with COVID is quite, quite stretchy. But I feel there's no evidence to support it. Our group published this study last year in nearly 2,000 patients hospitalized with COVID which looked at the incidence of post-discharge Venous thromboembolism. And we did not find post discharge VTE was increased compared to historical data. And subsequently, there have been and other couple of studies, smaller studies which reached the same conclusion. So I think the data of hospitalized patients do not show an increase in post-discharge Venous thromboembolism. Equally, I think outside of COVID times the evidence supporting extended thromboprophylaxis, but clearly with the use of direct oral anticoagulants is not strong. And this is not a practice that has been adopted generally, and is not in most of the guidance globally because the number needed to treat on the basis of the DOAC studies is something like one, seven, six. The number needed to harm is sixty. So it is not quite spread practice. And my current view is that we should not be using extended thromboprophylaxis as a routine. So clearly, I think we do have the option of taking an individualized approach if there are some persisting risk factors on this chart, you know, you have, for example, a patient with a poor performance status who is still very mobile or has risk factors like cancer, and you might in those cases consider, you know, giving thromboprophylaxis and low molecular weight heparin or a DOAC for a few weeks. Again, I'm aware there's some practices in which people are using D-timer at discharge to guide post-discharge thromboprophylaxis, but I do not think the evidence supporting that is particularly strong, and I would to advocate it routinely. Thank you.

04:28  - 05:20

Dr. Abhay Bhave

Thank you very much for that -- the thought process that you gave us. What we also need some guidance from you is that the government initiative is to see that vaccination is given to all, but in our media there is some discussion of patients developing low platelets and thrombosis after taking especially what we have in India that is the chimpanzee adenovirus AstraZeneca vaccine. And there's a lot of scare and confusion, and people are a little bit worried about taking it. So could you please tell our audience what is this vaccine-induced thrombotic thrombocytopenia, VITT? How much should we be worried about this? And would it be a reason for people not to take this vaccine?

05:21  - 08:36

Prof. Roopen Arya

Thanks, Dr. Bhave. This is a phenomenon that we first became aware of about a couple of months ago. There's an adverse immune reaction which seems to be -- to the adenovirus vectors whether it's in the AstraZeneca vaccine or the Johnson and Johnson vaccine. And it seems to be behaving very much like what we've seen in the past in heparin-induced thrombocytopenia where you get a lowering of the platelets due to this hyperimmune response in combination with a strong thrombotic tendency and manifesting as unusual site thrombosis quite often. Nearly half the cases we have seen have been of cerebral sinus thrombosis, but we have also seen other forms of venous thrombosis both typical and atypical, as well as cases of arterial thrombosis. Now we have given over 30 million doses of the AstraZeneca vaccine in the UK. So we have seen I think to date about 260 cases of this phenomenon. So it is very rare. I think the overall incidence is about one in 100,000 taken in the population as [inaudible 00:07:00] and maybe one in 50,000 in the under 50s. But it's important to be aware of this phenomenon because it is managed in a very particular way, the avoidance of platelets and avoidance of heparin by analogy with it, and using immune blockade in the form of intervention. So it's important to be aware of it if you see a very rare case, but I think it's equally important to realize that this is a very rare complication, and it is far outweighed by the very high thrombotic risk that is associated with actually catching COVID-19 disease, and the risk benefit is firmly in favor of having the vaccine. So it's very, very important that, you know, we don't overstate the risk due to this rare consequence. Yes, we should be aware of it in the rare chance that we have to manage a case. But the benefits of the vaccine are particularly in India today with numbers that of infected patient [inaudible 00:08:30] that the benefits far outweigh the risk of vaccine. Thank you.

08:37  - 09:08

Dr. Abhay Bhave

Prof. Arya, thank you very much for the insights on your -- on this topic of COVID-19 and coagulopathy. May I take the opportunity to ask a couple of more questions which would invest clinicians in India? One of them being that if a patient is on Warfarin or is on DOACs for any other reason, would it be a deterrent to take the vaccine? Should they be stopping the drug or can they go ahead despite the patient being on the anticoagulant?

09:10  - 09:46

Prof. Roopen Arya

If the warfarin is well controlled, then the INRs in the therapeutic range, and also with the black patient, they should go ahead and take the vaccine. There is not a significant increase in bleeding risk, but as a precaution, they should make sure that they press on the injection site maybe for three or four minutes just to ensure that the bleeding has stopped. But certainly, the patients who are fully anticoagulated should receive the vaccine, and it is safe.

09:48  - 10:15

Dr. Abhay Bhave

Thank you very much for that. And I also get questions from my patients who have experienced thrombosis in the past, and they're off therapy now. They've led a normal life without a recurrence of the DVT. But now they're a little bit anxious about this VITT, and they are worried whether they are prone to thrombosis, and whether they should take some form of anticoagulation for a temporary period of time. What's your thought on this?

10:14  - 10:39

Prof. Roopen Arya

Yeah. So there's no evidence that previous history of thrombosis or of thrombophilia increases, number one, you know, the risk of catching COVID, and number two, that it does not increase the risk of developing vaccine-induced thrombosis and thrombocytopenia in any way as far as we are aware.

10:40  - 11:24

Dr. Abhay Bhave

Thank you. So based on the pathophysiology you have told us, it appears that the reason of thrombosis in those VITT is different from what these patients have in terms of the inherited thrombophilia status. Thank you for clarifying that. And the last thing which is there on everyone's mind which has taken India by storm in the last couple of weeks, and that is what we have called as the black fungus. Mucormycosis is a problem for our patients who are on -- who receives steroids. So what's your thought process or what's the take-home message you're going to give us with regards to use of steroids or antifungals or the cohorts of patients?

11:25  - 13:35

Prof. Roopen Arya

Yeah. I think the awareness about Mucormycosis is very much allied and particularly in the media in India at the moment, and it is a very significant concern which I'm pleased to say, we don't see this condition in the UK. And so I think it has arisen due to some perfect storm as it were of the different risk factors. So in that you are in India more likely to have widespread exposure to the fungus in the environment which is less the case, you know, in the west. And the damage to the airway tissues, as well as to the blood vessels resulting from COVID-19 also does increase the susceptibility. The high background rates of diabetes in the population I think are reflected in the fact that the majority of cases to the black fungus, in fact, do have underlying diabetes. And then if you add to this widespread an indiscriminate use of steroids, you know, particularly in patients who do not require it in the community, I think this is all contributed to this problem with the mucormycosis or the black fungus. But I think it's a lesson to us all to stick to the evidence and also to avoid the polypharmacy that we have been seeing in the community where the widespread use, you know, and mildly affected people at home of drugs like steroids [inaudible 00:13:26] and Remdesivir, you know, when it is clearly not indicated, and in fact is more likely to cause harm [inaudible 00:13:34].

13:36  - 14:08

Dr. Abhay Bhave

Thank you very much for that, and thank you for sharing your insights with us and helping us better understand the issues of Venous thromboembolism including the pathophysiology of thrombosis in patients with COVID-19. I'm sure our audience will be very significantly benefited from this rich knowledge that has come from you and will help us to improve the outcomes in our patients. Before I let you go, Prof. Arya, are there any last thoughts you'd like to share on this topic for our listeners?

14:08  - 16:25

Prof. Roopen Arya

Thank you for that. So my take-home advice [not clear] is, you know, that there's little doubts that SARS Coronavirus-2 and COVID-19 disease is associated with an extraordinary burden of thrombosis. So be aware of the risk particularly in the hospitalized patients and use the appropriate prophylaxis, which in the majority of patients will comprise standard dose low molecular weight heparin. My second advice is to stick to the evidence base because there has been I think a huge acceleration of research during this time, but also sometimes an expectation to respond to the evidence before the paper has been published, and we've had an opportunity to analyze it. So I think the evidence is the evidence. So please try not to depart from it as far as possible. And VTE prevention and the use of anticoagulation is only one aspect of the overall care of the patients. I think the improvement in outcomes that we have been seeing is due to the incremental use of, for example, proning, hydration of the patients, the use of steroids, antivirals in the hospitalized patients. So the anticoagulation is only one component of that, and really I think the ideal approach to VTE prevention is to prevent the COVID whether it's through this social distancing and the PPE and taking all the precautions, as well as getting as much of the population vaccinated as possible. So I think the ultimate answer will lie in this system-wide approach to preventing COVID and then managing the patient care holistically if they are admitted to hospitals. I'll stop at that point. Thank you for attention.

16:25  - 16:59

Dr. Abhay Bhave

Thank you, Prof. Arya, for sparing time from your busy schedule and enriching us with your thoughts and experiences. I hope our listeners have enjoyed this interaction as much as we have enjoyed bringing it to you. Special thanks to Sanofi India for their continuing support in innovation and providing such knowledge-sharing platforms, which will go a long way in realizing our vision of VTE free India. So till the time we plugin again to another interesting episode of VTE Unplugged, stay safe, and stay healthy. Thank you.