Don't Just Read the Abstract

In this episode, Pip and Rich discuss the C-TRACT trial: Vedantham et al. Endovascular Therapy for Post-Thrombotic Syndrome — A Randomized Trial. 2026N Engl J Med 2026;394:2293-2304C-TRACT (Chronic Venous Thrombosis: Relief with Adjunctive Catheter-Directed Therapy) was a phase 3, publicly funded, multicentre, open-label, assessor-blinded RCT published in NEJM that randomised 225 patients with moderate-to-severe post-thrombotic syndrome (PTS) and imaging-confirmed iliac-vein obstruction to endovascular therapy (iliac-vein stenting + enhanced antithrombotic therapy) plus standard care versus standard care alone.Key ResultsAt 6 months, the endovascular group had a statistically significant reduction in PTS severity by the Venous Clinical Severity Score (VCSS: 8.1 vs. 10.0, adjusted difference −2.0 points; P=0.001). Quality-of-life scores also improved with a 14.5-point improvement in venous disease–specific QoL (VEINES-QOL) and a 6.1-point improvement in the SF-36 physical component summary with the intervention.However, bleeding was significantly higher in the intervention group (11.6% vs. 3.6%; P=0.03).In the episode, Pip and Rich discuss key critical appraisal points including:Modest primary endpoint difference. The 2-point VCSS difference, while statistically significant, is relatively small on a 0–30 scale. The clinical meaningfulness of this difference at the individual patient level is debatable, though the authors argue that many patients shifted to lower severity categories.Open-label design. The trial was open-label, which is a significant limitation for patient-reported outcomes like quality of life. While the primary outcome (VCSS) was assessed by blinded evaluators, the large QoL differences (which are the most compelling results) are susceptible to expectation and performance bias - a limitation the authors themselves acknowledge.Short follow-up. Results are reported at only 6 months. Stent patency, durability of benefit, and long-term safety (including stent-related complications and the consequences of enhanced antithrombotic therapy) remain unknown.The relevance of enhanced antithrombotic therapy which confounds the intervention. The endovascular arm received both stenting and additional antithrombotic therapy, making it impossible to disentangle the contribution of each component and likely explaining the higher bleeding rate.Generalisability. The trial was limited to patients with iliac-vein obstruction and moderate-to-severe PTS, a specific subset of the broader PTS population. Results should not be extrapolated to milder disease or non-iliac obstruction.

On this episode, Pip and Rich discuss the FRONTIER2, the phase 3 trial of Mim8 (denecimig) for prophylaxis in haemophilia A with or without inhibitors. They review the study design, efficacy and safety results, and consider where Mim8 may fit into the rapidly evolving haemophilia treatment landscape. They also explore the key unanswered question: does Mim8 offer any meaningful clinical advantage over emicizumab, or is its main benefit greater convenience through fixed-volume administration?

On this episode, Pip and Rich discuss the COBRRA trial: Castellucci et al. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. NEJM. 2026. The trial showed a convincing reduction in clinically relevant bleeding in patients treated with apixaban (3.3% vs 7.1%) and no difference in efficacy. It's a compelling study but there were important exclusion criteria and as ever, there are some nuances beyond the abstract. This episode also includes an update on Pip's daughter's school science project where unwitting families were invited for dinner to find out whether there is, indeed, always time for pudding.

Following its recent US FDA approval, on this episode, Pip and Rich discuss mitapivat, an allosteric activator of red-cell pyruvate kinase. They focus on ENERGIZE, a randomised controlled trial of mitapivat vs placebo (2:1) randomisation in people living with transfusion dependent thalassaemia. It met its primary endpoint of achieving significantly more patients reaching a haemoglobin rise of at least 1 g/L. However, Pip and Rich discuss the relevance of this surrogate endpoint as well as the small effects on fatigue and quality of life. Taher et al. Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): a phase 3, international, randomised, double-blind, placebo-controlled trial. Lancet. 2025 Jul 5;406(10498):33-42. doi: 10.1016/S0140-6736(25)00635-X.

On this episode, Pip and Rich VAY-HIT2, a trial recently published in the New England Journal of Medicine. This study randomised patients with relapsed/refractory ITP after first line corticosteroids to eltrombopag + ianalumab or placebo. As the thrombopoietin receptor agonists such as eltrombopag are often given for extensive periods, there's a lot of interest in giving additional treatment that can result in a relatively short course of treatment. Ianalumab is an anti-B-Cell Activating Factor (BAFF) Receptor monoclonal antibody. VAY-HIT2 was a phase 3, randomised, double-blind trial, assigning, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive eltrombopag + ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. The trial did meet its primary endpoint but there's a lot to discuss, most importantly the quality of life end points - and the interpretation is not straight forward!Conflict of interest disclosure here: Pip has received travel expenses and payment for attending an advisory board for Novartis. Pip is also leading a Novartis-sponsored UK audit of the treatment of warm autoimmune haemolytic anaemia on behalf of HaemSTAR (www.haemstar.org/TRUTH).

In this second of a two-part episode, Pip and Rich discuss their highlights of 2025. They discuss a wide range of developments across medical haematology with a focus on red cells disorders and a bit less naval gazing than the first episode.

In this first of a two-part episode, Pip and Rich discuss their highlights of 2025. They discuss a wide range of developments across medical haematology with a focus on bleeding disorders and immuno-haematology.

On this episode, Pip and Rich discuss two of their recent publications on idiopathic and secondary polycythaemia. The first is an audit across two large hospitals in the Midlands. The team screened over 2000 patients who had had a JAK2 mutation screen performed, eventually finding 266 with confirmed idiopathic or secondary polycythaemia. By the time patients were seen, the haematocrit was already dropping. 60% were never venesected and venesection seemed to make no difference to haematocrits and had no association with thrombotic events. In the second paper which was a survey of clinicans, practice was, as expected, shown to be variable. 85% responded to say that they would be willing to randomise patients to a clinical trial of venesection vs no venesection.This is an interesting discussion on a common situation for which there is almost no academic interest whatsoever. However, it is a big clinical problem - there is a lot of work for haematologists here. The evidence does not support treating this group of patients in any way shape or form and a trial to prove non-inferiority of no venesection is very much needed.Here are the links to the papers: Maybury et al. Venesection and resolution of erythrocytosis are not associated with reduced thrombotic risk in secondary and idiopathic polycythaemia: Results from a dual centre, 5-year retrospective study. Br J Haematol . 2025 Sep;207(3):1127-1132. doi: 10.1111/bjh.20235Nicolson et al. Common Themes and Uncertainties in Management of Secondary Polycythaemia: An International Clinician Survey of Practice. EJHaem . 2025 Oct 27;6(6):e70171. doi: 10.1002/jha2.70171