Tales from the 2023 International Society of Thrombosis and Haemostasis meeting in Montreal

As a core medical trainee aspiring to secure a spot in Haematology training, one of the things I had eagerly anticipated was the opportunity to attend international conferences and connect with haematologists from all around the world.

Becoming a specialty registrar amid the COVID-19 pandemic meant no face-to-face meetings or international conferences during the initial part of my specialty training. While online meetings became the new norm and reshaped the way we work and communicate, I welcomed the return to in-person meetings with immense relief.

I am still filled with gratitude for being able to see people face-to-face, stroll amongst posters, and present my research in person, rather than through a screen. This overwhelming sentiment animated me during ISTH 2023 this year.

My excitement was palpable as I boarded my 7-hour flight to Montreal, and I had already marked on my calendar all the lectures I wanted to attend, focusing heavily on gene therapy and obstetric haematology.

The quality and volume of research presented were jaw dropping. Some highlights from the lectures I attended include:

-The haemophilia basic science sessions on FVIII and FIX, where the German group from the University of Bonn presented intriguing research on intracellular trafficking of full-length versus B-domain deleted FVIII. Matthew Cormier's presentation on the relationship between gut microbiota and the risk of developing FVIII inhibitors in a mouse model during the second basic science session on Monday.

-I also thoroughly enjoyed the SSC women's health session, particularly Dr Rohan D'Souza's lecture on understanding the decision-making process for anticoagulation choice in pregnant patients with mechanical heart valves.

-The haemophilia gene therapy sessions for haemophilia A provided valuable updates from GENEr8-1 and SPK-8011 trials, along with an overview of the gene therapy WFH registry by Professor Barbara Konkle.

Amidst the lectures, I had the chance to network with many clinicians and scientists from around the world. During the poster session, I reconnected with a colleague from La Sapienza University in Rome, with whom I graduated in 2016. She is now a specialist in Internal Medicine with an interest in haemostasis & thrombosis. I enthusiastically shared information about HaemSTAR and my desire to collaborate internationally with Italy, and she quickly thought of also involving her colleagues from the Netherlands, where she had conducted research in the past.

Me and Rossella Talerico, from Policlinico Gemelli in Rome, remembering our university years and thinking about ways of collaborating in the future.

Another significant highlight was connecting with the Haemostasis and Thrombosis Research Society, a scientific community based in North America dedicated to research, mentoring, networking, and medical education in haemostasis and thrombosis. On a beautiful sunny Sunday, I met with Barbara Lam and Justine Ryu to discuss our shared interests in non-malignant research and how HaemSTAR and HTRS could collaborate in the future, paving the way for international trainee collaborations.

Over tasty panini (and losing track of time), we realized the immense potential of joining forces between our two networks that share similar goals and scientific/educational missions.

Later, we attended the early career mentoring session, where we met with the early career committee. Barbara and I pitched our plans to form international connections among trainees and early career researchers with great enthusiasm. It would be wonderful to have a dedicated session on trainees' networks worldwide at ISTH 2024 in Bangkok!

Crashing the HTRS meeting – that Matcha latte was amazing!

Leaving Montreal, I felt overwhelming gratitude and confidence in the future. I eagerly anticipate transforming these connections into long-lasting scientific collaborations.

I am reminded of something Professor Cuneo, head of the Haematology unit in Ferrara, wrote to me in 2017 when I was leaving Italy for the UK. With his words, I want to conclude as it perfectly summarizes my feelings post ISTH.

My Vision for HaemSTAR

It’s an immense honour to take over from Pip Nicolson as HaemSTAR chair. Pip has led us over the last six years from inception and has grown HaemSTAR into a real force to be reckoned with. Whilst we have thus far had tremendous success, it is not time to rest on our laurels. Rather, it is time to harness the energy and momentum that Pip has built up and transform HaemSTAR into something even more powerful.  

Producing Impactful Change 

Both Pip and I agree that the real point of clinical research is to produce impactful change for the better. Whilst our large-scale audits and observational studies add much value and will continue, we need to focus on how we best make use of the finite resource that is our collaborators. Thanks to our amazing collaborators – registrars, other junior doctors, and plenty of consultants – HaemSTAR can do things that very few other organisations can do. That’s why we want to harness this and lead projects that can inform better care. To this end, Pip will set up HaemTRIAL, a parallel network that will work in partnership with HaemSTAR to perform prospective studies. The HaemSTAR committee have already met to brainstorm ideas and we have three potential projects: 1) Randomised trial of venesection versus no venesection for idiopathic and secondary polycythaemia; 2) Randomised trial of blanket screening for antiphospholipid syndrome in patients with unprovoked VTE; 3) a randomised trial of tranexamic acid in heavy menstrual bleeding. These will all be fleshed out and discussed further in due course with the intention of applying for funding. 

Professionalising HaemSTAR 

HaemSTAR has grown from something that could easily be managed by a handful of people to a machine that has many moving parts and requires a good deal of management. Pip is tremendously organised – a quality that I cannot replicate. We have therefore unanimously decided to employ an administrator who will at first work four hours a week to answer emails, arrange meetings, and perform other day-to-day admin tasks. We are delighted that we have recruited Helen Apperley to this post. Helen is attentive and diligent, and will be a fantastic addition to the team. 

Widening Access to Research 

There are many ideas and many people in search of projects. HaemSTAR can help bring these together by creating a project matchmaking page on our website. Expansion of the network will continue, especially among doctors and registrars, with a focus on fostering relationships that could lead to research partnerships. We will help set up parallel networks of nurses and allied health professionals, facilitating their involvement in research projects. 

Widening Access to Research Through Education 

I am keen that we provide a small educational offering by inviting inspiring speakers to deliver talks via a free, monthly Webinar that will take place on a weekday morning 8:30 – 9:00 (not clashing with the excellent UKHCDO programme). The idea of these is to bring you really interesting speakers that will be more idea and research focussed than pure content. We have some really engaging talks lined up and this will be launched soon. 

We have also applied for funding to produce a monthly journal club podcast. More details will follow if this is awarded.  

Funding Travel and International Collaboration 

We are excited that we have been awarded $37,500 from the ISTH London 2022 legacy fund. This will go towards awarding travel grants ($25,000) and setting up international collaborations ($12,500). Information on eligibility and how to apply for this funding will be on our website shortly. 

Improving Engagement with Regional Representatives 

We have some wonderful regional reps but thus far have not been too good at engaging with them. In the last year, Pip and I have made a point of meeting with all new regional reps to introduce ourselves, the concept of HaemSTAR and what we would like them to do. This has helped but we also intend on having an online meeting twice a year to update on projects and promote a two-way conversation. The details for the first meeting which will take place in September will be released soon. 

HaemSTAR Prizes 

We know that some of you put in immense amounts of effort and work into the things that you do, consistently going above and beyond your day job. It is important to recognise and reward this excellence and I am pleased to announce that prizes will be awarded at our annual meeting in 2024. The exact nature of these prizes is yet to be determined but will likely include awards such as project of the year, HaemSTAR rep of the year, and non-malignant haematology educator of the year. 

Working with Industry Partners 

Working with industry can often be contentious but I feel it is both necessary and mutually beneficial to continue to develop our industry links in a way that maintains our integrity but allows us to do fantastic work. The RAPIDO project is a good example of how to work with industry. AstraZeneca have provided £90,000 funding for the project with academic control of the project remaining with us. This shows that where interests align, there are huge opportunities. Of course, we will remain vigilant to exploitation and seek advice from senior academics where appropriate. 

HaemSTAR is yours

No matter what my goals are for HaemSTAR, it remains an organisation for you. We are here to offer opportunities to get into research and to promote non-malignant / classical haematology. If you have an idea or want to find out more, just send me an email - richard.buka@nhs.net.

If you want to read more of my musings mostly about classical/non-malignant haematology, follow my blog on Substack.

The Woes and Wonder of Immunohaematology in the United Kingdom

In recent years there has been an increasing expansion of haematologists with an interest in immune-mediated disease within the classical haematology world. This has been driven by an increased knowledge of these conditions and novel targeted treatments that are now available. However, it has become apparent that an abundance for some conditions is balanced by limitations for others.

First, let us start with the wonders: thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenia (ITP). TTP is a devastating and life-threatening diagnosis albeit a rare one. In the last year, NHS England has recognised this with the development of a national TTP framework providing regional access to 24-hour plasma exchange services by experts in its diagnosis and treatment. The use of caplacizumab, a nanobody that reduces von Willebrand factor-platelet binding, has been approved with the TITAN and HERCULES studies showing improved outcomes when added to plasma exchange and immunosuppression. The use of rituximab in treating sub-clinical ‘ADAMTS13’ relapses has also become standard of care in the UK TTP Network. Results from the nationwide UK TTP registry and on-going recruitment in the UK-led ERTTP study will give clinicians further information on dosing options.

ITP is likely to be the most common condition faced by the immunohaematologist. It still lacks a specific diagnostic test but due to its higher incidence, clinicians have more experience and are comfortable in its treatment. Refractoriness or loss of response is one of the key concerns for clinicians but the arsenal of therapies available to treat the condition has increased over the last decade. The TPO receptor agonists, romiplostim, eltrombopag and avatrombopag, as well as rituximab are now being used earlier and with greater confidence. Fostamatinib, a SYK inhibitor, has recently been approved by NICE and the HaemSTAR-supported FLIGHT study gave support for the early use of mycophenolate with steroids at the time of diagnosis. A combination of better clinical data for ‘old-fashioned’ drugs and the industry development of new targeted therapies has helped to transform the list of treatment options. Excitingly, HaemSTAR is now working with industry to trial novel immunosuppressants in this space.

Let us now turn our heads to the woes: antiphospholipid syndrome (APS) and acquired haemophilia A (AHA). APS is a prothrombotic condition causing venous and arterial thromboses as well as obstetric morbidity. Its problems at present lie in several areas: 1) its multi-headed nature making clinical or surrogate end-points difficult to assess in clinical trials, 2) poor outcomes in anticoagulation studies, and 3) the lack of a clear molecular target. Assessing the surrogate markers of thrombin generation assays in the TRAPS study comparing warfarin to rivaroxaban, failed to translate into safe patient outcomes. DOACs have become the standard of care in the 2020s for treating venous thromboembolism in the UK however due to the findings from the TRAPS study, warfarin still remains the preferred anticoagulant for APS. Similarly, varying forms of immunosuppression have yet to show clear benefit. The HaemSTAR supported A2PLS audit has provided a snapshot of current practice in the UK and publication is eagerly awaited. Although there is recognition that β2-glycoprotein plays a key role in the condition, antibodies to the protein are not seen in all patients and its physiological and pathogenic role are still poorly understood. These issues remain a key barrier to the treatment of this disease.

Finally, acquired haemophilia A (AHA). Similar to TTP, this is rare but treatment options are less well tested and the field is plagued a lack of prospective data. Control of bleeding and immunosuppression are key. Rituximab has shown some benefit for AHA, similar to other immune-mediated conditions, but large multi-centre data has yet to be presented and the risk of subsequent relapse is less clear. The EACH2 Registry helped to give better understanding of the impacts of cyclophosphamide and steroid for the disease. Factor VIII bypassing agents including FEIBA and recombinant factor VIIa, are used but they are non-specific, can be problematic to administer, and there is a lack of experience in non-specialist haemostasis centres; surely, these must impact upon patient outcomes. Emicuzimab, a bivalent FVIII-mimicking monoclonal antibody, has revolutionised the bleeding experience of patients with cogenital haemophilia A with inhibitors. However, despite anecdotal evidence and case reports, industry-supported prospective studies for AHA have yet to materialise. It is only in Japan that emicizumab is licences for AHA.

Going forwards there is a clear need to better understand the underlying disease processes in these conditions in order to develop targeted therapies. Along with this, clinicians need to be able to engage with industry to improve the treatment of these rare or neglected conditions. However, it takes many years drug development to bring these therapies from bench to bedside. Developing clinical care networks to support research in immunohaematology has shown benefit in some of these diseases. Surely, this must be applicable to others on a national scale to focus clinical research questions, rationalise currently available treatments and improve patient outcomes.

Diving into clinical academia: what’s holding you back?

This blog is for all those out there who feel like they don’t have their ‘foot in the door’ of clinical academia, or who are feeling the very well-known ‘imposter syndrome’ when they think about getting more involved in research.

Good news – there’s no reason why you can’t get involved in research later in your training career. From my own experience, I had not undertaken an intercalated degree nor any research whilst at university (isn’t the medical degree enough?!), and had never been in an academic training post – but, I was really interested in clinical research and what it involved, and actively sought out opportunities with my colleagues by expressing a keen interest. With the help of supportive and encouraging mentors and consultants, I was able to go out of the haematology training programme to do a PhD in April 2019, and I haven’t looked back since.

I have always believed that the more you put into any aspect of your life, the more you will get out of it, and this most definitely includes in your career. No-one can deny that those first steps into clinical academia can be daunting; it is a very steep learning curve, a whole new language and way of working – but there are plenty of us around who will happily talk about the highs and lows of our career journey so far and share in all your sentiments! I’ve had the chance to meet so many different people from across the country through the HaemSTAR network, made good friends and had so many uplifting conversations about our shared experiences.

So, if you are interested and keen in being involved in clinical research, at whatever capacity that may be, don’t be put off – don’t compare yourself to what others may have done - and do grab every opportunity that comes your way. We all have our individual strengths to bring to the table, and research really can be for everyone.

2023 HaemSTAR Meeting Highlights

Writes Dr Eman Hassan, Haematology Registrar, West Midlands

Finally, after a long four years of waiting, on Monday 6th February, HaemSTAR members had the chance to get together for a face-to-face meeting. The event in Newcastle upon Tyne was tagged to the popular ASH/ISTH non-malignant highlights day, making the journey even more worthwhile.

It was an exciting opportunity for people of different backgrounds to come together to share experiences, get the most recent updates on HaemSTAR projects, and listen to some compelling educational content delivered by experts in classical haematology. A wide variety of delegates attended including junior doctors, haematology trainees, consultants, pharmacists, clinical scientists, and industry representatives. The meeting was also streamed online for those unable to attend in person to ensure no one missed out.

The meeting started with a warm welcome from the HaemSTAR chair Pip Nicolson, and this was followed by a rich session about current and future HaemSTAR Projects. Lorna Cain presented initial results from the national Two Sample Rule survey which has been supervised by Dr Suzy Morton, Birmingham. The survey was circulated end of last year to ED doctors through HaemSTAR leads. Strikingly, results showed poor understanding of the reasons for the Two Sample Rule; two thirds had taken two samples from the same blood draw and labelled them with different times. This had a lot of interest on Twitter! Full results will be presented at the BSH ASM this year.

Following this, Christina Crossette-Thambiah, presented results from A2PLS study, which was also presented at the ASH meeting at the end of last year. This project was conceived and supervised by Dr Deepa Arachchilage. A2PLS is a national audit of antiphospholipid syndrome to assess national practice. It included 500 patients and to our knowledge is the largest cohort of APLS patients ever. It found a 40% risk of recurrent thrombosis at 10 years, higher in arterial thrombosis. Interestingly, the risk of thrombosis recurrence with lupus anticoagulant positivity was same as triple anti-phospholipid positivity. The manuscript is in preparation.

Becks Shaw then presented data from the ConNeCT study – a questionnaire-based study on long term neurological complications in TTP which is supervised by Dr Tina Dutt, Liverpool. 30% of patients recruited had moderate-severe depression. The study is still recruiting, and enthusiastic trainees were encouraged to get involved.

The final talk of the session was an update from Pip Nicolson on three randomised trials that HaemSTAR are supporting – testing the utility of Ianalumab, an anti-B cell activating factor (BAFF) monoclonal antibody. Two studies are in ITP and one in warm autoimmune haemolytic anaemia. Already, HaemSTAR members have helped set up sites.

After lunch, our educational session kicked off with haematology consultant, Noémi Roy, gave an inspirational lecture on the pain in sickle cell disease. The talk concluded with a call to action – can HaemSTAR support patient driven studies for better pain control?

Next, we welcomed Ian Roberts who ran many of the large trials on tranexamic acid including the CRASH and WOMAN trials. Ian gave an update on tranaexamic acid use in trauma, major haemorrhage, post-partum and surgery, and discussed that despite the strong evidence of benefit, tranexamic acid remains under used.

Following on from Ian’s talk, we held a discussion forum, breaking off into small groups to discuss the workings of HaemSTAR and how to make an impact. These discussions were constructive and allowed thoughts and plans to evolve.

In the final session, Vickie McDonald presented the output from the more than 5,000 patient strong UK adult ITP registry with a focus on how treatment of ITP changed during the COVID-19 pandemic. The registry has a lot of potential for answering further research questions and anyone interested in analysing data can contact Vickie.

To close the day, Richard Buka presented interim results of RAPIDO audit, our national project looking at the use of reversal agents for DOACs. This was presented in the context of a talk on the weak evidence for DOAC reversal. Thus far, RAPIDO has collected data on 837 patients, median age 81, 88% of whom received PCC. Mortality was high at 40%. Early results show heterogeneity of practice. More data will be collected in Autumn 2023.

We would like to thank all the delegates and speakers for attending what we think was a great event. We are really looking forward to seeing some of you at the BSH ASM in April in Birmingham and we plan to run this meeting annually.

If you would like to find out more about our projects, check out our Past Projects and Current Projects pages; or email haemstarnetwork@gmail.com.