ThinkSono are a UK-based company providing an innovative solution for the diagnosis of DVT

On this episode, Pip and Rich chat to Fouad Al Noor, CEO of ThinkSono. ThinkSono have developed an AI-powered handheld scanning tool for DVT that enables anyone to perform a diagnostic quality ultrasound scan for the diagnosis of DVT. The images are then reviewed by a radiologist, providing a rapid answer for most patients. The tool is entering use within the NHS and in this podcast, Pip and Rich discuss the story and the evidence behind ThinkSono as well as the challenges and opportunities that the tool provides. For more information, visit <a href="www.thinksono.com" rel="noopener noreferrer" target="_blank">www.thinksono.com</a> and to access the evidence, head to <a href="www.thinksono.com/research" rel="noopener noreferrer" target="_blank">www.thinksono.com/research</a>. Pip and Rich have no relevant conflicts of interest for this episode. The podcast was initially started thanks to a hands off grant from Sobi who have had no editorial input into the show.

AI powered ultrasound for DVT - an interview with CEO of ThinkSono, Fouad Al Noor

Rich and Pip critically appraise de Latour et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. NEJM 2024

In this episode, Rich and Pip discuss <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2308695" rel="noopener noreferrer" target="_blank">de Latour et al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. NEJM 2024</a>. Iptacopan is a proximal complement inhibitor and the first oral treatment for paroxysmal nocturnal haemoglobinuria. The study randomised patients to either continuation of a C5 inhibitor or switch to ictacopan and found that a significant proportion of patients achieved hemoglobin levels of 120 g/L or higher without the need for transfusions. The treatment was generally well-tolerated, with a safety profile consistent with previous studies, suggesting that iptacopan is a viable alternative to existing therapies. Join us as we delve into the study's methodology, results, and implications for the future management of PNH.

Iptacopan for PNH

In this episode, Pip and Rich discuss plasma exchange free treatment of thrombotic thrombocytopenic purpura with Dr Lucas Kuhne and Professor Paul Brinkoetter, authors of a recent study in Blood: <a href="https://ashpublications.org/blood/article-abstract/144/14/1486/516366/Management-of-immune-thrombotic-thrombocytopenic?redirectedFrom=fulltext" rel="noopener noreferrer" target="_blank">Kühne et al. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange.</a> The study is an observational, retrospective study reporting outcomes of patients with TTP who were treated without plasma exchange, which is currently considered the standard of care. The advent of a novel nanobody against vWF called caplacizumab, that targets and prevents catastrophic thrombosis that is seen in TTP, has allowed the study of this approach.

Plasma exchange free treatment of TTP: Author Discussion

Discussion of Kühne et al. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange. Blood. 2024

In this episode, Rich and Pip discuss a paper a German/Austrian study published in Blood: <a href="https://ashpublications.org/blood/article-abstract/144/14/1486/516366/Management-of-immune-thrombotic-thrombocytopenic?redirectedFrom=fulltext" rel="noopener noreferrer" target="_blank">Kühne et al. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange.</a> The study is an observational, retrospective study reporting outcomes of patients with TTP who were treated without plasma exchange, which is currently considered the standard of care. The advent of a novel nanobody against vWF called caplacizumab, that targets and prevents catastrophic thrombosis that is seen in TTP, has allowed the study of this approach. Rich and Pip discuss the nuances of the paper and offer critical analysis. In a follow-up episode, Rich and Pip will interview the study authors.

Plasma exchange free treatment of TTP

In this episode, Rich and Pip discuss gene therapy for sickle cell disease, focusing on <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2309676" rel="noopener noreferrer" target="_blank">Frangoul et al. Exagamglogene Autotemcel for Severe Sickle Cell Disease, NEJM 2024.</a>

7. Exa-cel for severe sickle cell disease

In this episode, Pip and Rich discuss ANNEXA-I with Dr Will Lester, consultant haematologist at University Hospitals Birmingham. ANNEXA-I was a randomised controlled trial of andexanet alfa for reversal of anti-FXa oral anticoagulants in patients with intracerebral haemorrhage. There's a lot to get your teeth stuck into so and this one is a lively discussion! Disclosure: Pip and Rich are named investigators on a grant from AstraZeneca to audit the use of reversal agents (including andexanet) across the UK. Pip has also received honoraria from AstraZeneca. Will has received honoraria from AstraZeneca. To see our full list of financial disclosures, search for us on Who Pays This Doctor.

ANNEXA-I: Discussion with Dr Will Lester

Pip and Rich discuss the ANNEXA-I trial of andexanet alfa for oral factor Xa inhibitor-associated intracerebral haemorrhage

In this episode, Rich and Pip discuss the ANNEXA-I trial (https://www.nejm.org/doi/full/10.1056/NEJMoa2313040). This was a randomised controlled trial of andexanet alfa, a decoy factor Xa molecule that is a reversal agent for oral factor Xa inhibitors. Patients were randomised to andexanet alfa or usual care. The primary outcome was haemostatic efficacy and andexanet alfa was shown to result in better control of haematoma expansion compared to usual care. However, there are many discussion points here not least the validity of the surrogate outcomes used in the trial. Disclosure: Pip and Rich are named investigators on a grant from AstraZeneca to audit the use of reversal agents (including andexanet) across the UK. Pip has also received honoraria from AstraZeneca. To see our full list of financial disclosures, search for us on Who Pays This Doctor. In the next episode, Pip and Rich will discuss ANNEXA-I with Dr Will Lester. There is also a tiny mistake in the news section where Pip says that the infected blood inquiry report is 1200 pages long where in fact it is over 2500.

ANNEXA-I

Rich and Pip discuss the latest research in VITT and HIT including Schonborn et al. Blood, 2023.

In this episode, Rich and Pip discuss vaccine-induced immune thrombotic thrombocytopenia and heparin-induced thrombocytopenia. They critique a recent paper that has shown that VITT has been around before vaccines against Covid-19. Importantly, they discuss which patients should be tested for spontaneous VITT- and HIT-like syndromes, and discuss a recent case. The paper is: Schönborn L. et al. Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure. Blood. 2023 Dec 28;142(26):2305-2314.

VITT, HIT, and spontaneous syndromes

Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial

In this episode, Pip and Rich discuss the ADVANCE IV trial: Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia: a multicentre, randomised, placebo-controlled, phase 3 trial. With the help of Professor of Immunohaematology, Prof. Nikki Cooper, Rich and Pip dissect the trial, learning loads about ITP and the difficulties of doing trials in this space. Links: <a href="https://pubmed.ncbi.nlm.nih.gov/37778358/" rel="noopener noreferrer" target="_blank">Broome C et al. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Nov 4;402(10413):1648-1659</a>

Efgartigimod for ITP

Go beyond the abstract and enrich your learning

Want to stay up-to-date on the very latest developments in non-malignant haematology? Don't have the time or skills to critically appraise important papers? Join Pip and Rich, two haematology doctors on a journey of learning and discovery. Each episode, they will discuss a seminal trial, critically appraise the paper, interview a study author, and discuss the implications of the trial on clinical practice with a subject expert. CPD credits are available from RCPath. The podcast is sponsored by Sobi as a hands-off educational grant. Sobi have no editorial input whatsoever. This podcast helps you to go beyond the abstract, delving deep into the methods, results, subanalyses, and implications. Interviews with authors gives a real-life perspective on the running of a clinical trial allowing explanations of why they did what they did and good honest discussion on limitations and how they might do it differently next time.

Don't Just Read the Abstract

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