As the overall cancer death rate has declined over past decades and cancer survival has increased, unforeseen challenges are emerging. Thrombocytopenia, often associated with cancer disease or anticancer therapy, will be more present in thrombotic cancer patients, but evidence on how to treat these patients is lacking. Prof Anna Falanga discusses these Guidelines with host Dr Stephen Hibbs in this HemaSphere Podcast episode.  You can find the referenced article, in full and open access, here on the HemaSphere website, or watch the video on our YouTube channel.

00:14 Stephen Hibbs: Welcome to this episode of the HemaSphere podcast. My name is Stephen Hibbs and I'm a hematologist and clinical research fellow based at Queen Mary University of London; and I am one of the scientific editors for HemaSphere.

In today's episode, we will be discussing a common but challenging sect of clinical scenarios. What do you do when a patient with cancer and low platelets also has an indication for antithrombotic drugs? They might have had venous or arterial thrombosis.

Well, you might be considering treating them prophylactically.

How do you balance the risk profiles of different medications, different severities of thrombocytopenia and different indications for treatments?

Anna is Professor of Hematology at the University of Milano-Biccocca and works clinically at the Hospital Papa Giovanni XXIII in Bergamo.

Anna, could you start by telling us how you first became interested in this subject?

01:22 Anna Falanga: Yes, thank you. I am very pleased to be here with you and share some of the thoughts that we had when we were just preparing these guidelines.

I have been involved in the field of cancer thrombosis for a long time and, as you say, the cancer patients are at high risk of both arterial and venous thrombosis. But they also suffer with atrial fibrilation with ageing and everything.

So there are several circumstances here which we need to administer anticoagulation, or antiplatelet agents, to these patients.

But there are several factors that render difficult regarding these treatments in cancer patients. And, thrombocytopenia is one of these factors. It's a very well-known limiting factor for the mystery of anticoagulation in general.

But it can commonly occur in patients with cancer, due to the bone marrow infiltration by the cancer cells, or also through the anti-cancer treatments, high dose chemotherapy and all these kinds of things.

So, thrombocytopenia is a strong factor for the clinical use of anticoagulation or antiplatelet therapy. And different strategies must be undertaken to be able to provide, in a sense of protection against thrombosis, to these patients; without causing hemorrhage.

So this is a very, very challenging situation. We have to kind of really balance the risk of bleeding against the risk of thrombosis.

So there is a way, but very little evidence-based, if any, to help in this decision; and therefore, it needs much attention. And this is why we started --

This, of course, challenged me as well as the other clinicians.

03:24 Stephen Hibbs: So the timing of this guideline that you've published last year... What would you say have been the most important findings or changes, or new evidence, in the years leading up to making it a guideline?

03:38 Anna Falanga: Well actually, the challenge wasn't the lack of evidence-based data. Nothing particularly special has been coming out in the last years about that.

The only things that appear - so they were very clear throughout the research and the literature - is the great heterogeneity, or the approach of clinicians, in managing patients with severe thrombocytopenia and acute thrombosis, or in need of an acture treatment with antithrombotic drugs.

The scenario is very varied, very diverse... And for this reason we, the EHA, the European Hematology Association, in collaboration with the European Society of Cardiology, decided to produce this consensus guideline... because it cannot be called an evidence-based guideline. It's a consensus guideline to help clinicians in the decision-making for these patients.

We have learned - and it is a real need for the clinical practice.

04:46 Stephen Hibbs: On that kind of topic of a consensus guideline and, I guess, that being quite a different thing in some ways than a sort of fully -- Just working from lots of trial data-type guideline... What was the process like?

In particular, I'm interested to know if there are any areas where it was really hard to find consensus between the different members of the guideline writing group? Were there any parts of it where there were such strongly different views that it was hard to know how to come to a consensus? How did you approach that?

05:18 Anna Falanga: Well, these guidelines are focused on adult patients with cancer and the clear indication for anticoagulation, or for antiplatelet, or dual antiplatelet -- Single or dual antiplatelet therapy, or a combination... with concurrent thrombocytopenia.

This is, per se, an extremely challenging situation. So in my practice, I mean, the most challenging scenario since I am a hematologist, is the patients with acute leukemia or other hematological malignancy and the treatment with high-dose chemotherapy; who experience an acute thrombotic episode, like a pulmonary embolism or an acute myocardial infarction or stroke. This is, in any case, extremely challenging.

So we are just on the cutting edge of this problem. I cannot say that one scenario is worse than the other. This consensus guideline focuses exactly on the worst scenario we can have. And this is a particularly difficult one, when the platelets drop below fifty thousand and then even lower than that; below twenty thousand.

At that time, you clearly have to stop any treatment - and this; reducing the dose or to stop the antithrombotic therapy is a very, very hard decision.

06:56 Stephen Hibbs: So how does a guideline like this get written? What happens in terms of the consensus discussion? What does that look like? How do you go about that?

07:09 Anna Falanga: Yeah, as you can imagine, the debate has been often very heated in several circumstances, given the scarcity of evidence-based data on which to base our recommendations. So we use the Delphi procedure, which is the panel of experts who are engaging and several rounds of questions about how to make the decision and their responses are then aggregated and shared with the group after the round; until the consensus was achieved.

So this is the method that was utilized... because you can imagine that, very often, we had difficulties in finding an agreement.

07:53 Stephen Hibbs: I'm kind of struck by how complex this area is for us as clinicians and how difficult we find it to come to understand what to do. And so, I'm wondering what it would feel like to a patient when you're trying to explain to them the risks and the benefits and how you weight these things up.

Do you have any kind of advice about how you approach these sort of discussions with patients to make really complicated sort of risk-benefit discussions understandable to the patients that you are treating?

08:25 Anna Falanga: Yeah. This is a very important question because the most challenging time is when you have to communicate to the patient the circumstances. I would start with explaining to the patients the role, the job that the platelets do in normal conditions and the way they stop, very simply; the way they stop the blood loss in our body.

And then, of course, say that the small number of platelets, of course, render this situation at high risk of bleeding. And at the same time, they are already at risk of bleeding because they are taking antithrombotic drugs and they know that this is already at a risk of bleeding. This whole bleeding situation.

So the two things together are very, very difficult to manage - and this is why we have to try to find some strategies to help him or her to combat thrombosis without worsening the bleeding possibility.

09:39 Stephen Hibbs: Yeah. I can imagine that in practice it's very hard, isn't it?

09:44 Anna Falanga: Yes.

09:45 Stephen Hibbs: With everything kind of being different. But I guess that's it. We have to share that uncertainty with them, to say --

09:46 Anna Falanga: Yes.

09:48Stephen Hibbs: This is simple. This is part of it.

09:54 Anna Falanga: Yes. And this variant... we don't know. There are two very difficult situations together. And probably understanding why the background -- What the background is behind these difficulties can help us to understand also; the final decision that we have to share together.

10:14 Stephen Hibbs: So from the sort of situation we're in now where there's big gaps in the evidence base for this topic, I'd like to ask you: If you could have as much money as you wanted, as many researchers as you wanted, access to any patient report you wanted... What would be your dream study that would answer, sort of, the most important uncertainty here?

10:37 Anna Falanga: Yeah. I think that clinical studies in this field are highly needed. Many, many studies are needed. I would start, for my personal background, with an issue of cancer patients with severe thrombocytopenia grade three or four and acute venous thromboembolism.

I would start from that because, for me, a clinical trial is assessing the proper anticoagulation dose reduction, as compared to full dose, and also assessing the efficacy of platelet transfusion would be very urgent and also very helpful for our clinical practice because to provide information that can be extrapolated for a decision and also in other acute situations.

So probably I would give the preference to this type of trial, as first. So of course, for doing this type of trials, an international corroboration is crucial to achieve the goal.

11:51 Stephen Hibbs: Brilliant. I really hope that you get to do it, Anna. That sounds like a crucial study. If I can ask you... Is there any kind of final take-home message that you'd want to give to clinicians who are dealing with this sort of situation today?

12:05 Anna Falanga: The things that are -- I think about things that are simple but sometimes it's not easy to remember. The first thing to do from a hemostasis point, or coagulation point of view, is to assess the indication; to reassess the indication to the antithrombotic therapy; because sometimes the therapy is not necessary anymore. We can stop it - and so the problem is resolved.

You have to reassess the risk of thrombosis and the risk of bleeding or syncopations, of course. And also, anticipate the duration of the severe thrombocytopenia to make a clear plan for the management of the other thrombotic treatment.

And finally, I would say... Do not forget to restart antithrombotic therapy once the platelets go back to a reasonable over 50,000. Please don't forget to restart antithrombotic therapy.

These would be the things that I would suggest first.

13:15 Stephen Hibbs: Yeah. That's really useful. There's all the complex stuff that we don't have enough trials for and so on. But there's actually simple stuff that is just really hard to remember when there's so much other stuff going on.

So, thank you so much Anna for speaking with us today.

13:30 Anna Falanga: Thank you. Lovely... Thank you. Bye bye.

13:32 Stephen Hibbs: Thank you - and thank you to everyone listening to this podcast, so you can learn more from this guideline on the HemaSphere site. Please feel free to suggest other topics or articles you'd like us to explore on future episodes of this podcast.