Don't Just Read the Abstract

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.

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.

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.

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: 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

In this episode, Pip and Rich discuss the FRAIL-AF study: Joosten et al. Safety of Switching From a Vitamin K Antagonist to a Non–Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. Circulation. 2024;149:279–289.This trial randomised the switching of elderly frail patients who were established on a vitamin K antagonist to either remain on this treatment or switch to a direct oral anticoagulant. They found increased rates of bleeding in the switch arm. However, there is a lot of detail that is not in the abstract! Pip and Rich take a deep dive into the manuscript, discuss their thoughts with Chief Investigator, Geert Jan Geersing on the trial, and put the findings into context with consultant haematologist David Sutton.To read more about this trial check out Rich's blog on it: https://classicalcompass.substack.com/p/frail-afLinksFRAIL-AF: https://www.ahajournals.org/doi/epdf/10.1161/CIRCULATIONAHA.123.066485