Despite my musical tastes aligning more with Gen X, having been born in 1982 I’m apparently a millennial (according to Wikipedia anyway). Clinically, I have been “raised” in a much different world of hemostasis than my mentors. As I’ve mentioned before, I see patients making the transition from pediatric to adult care. These Gen Z folks have been largely unaffected by HIV, most of them have pretty healthy joints (courtesy of prophylactic factor since early childhood), emicizumab has made bleeding a thing of the past for many patients with hemophilia A, and all of them expect to lead a mostly healthy life like anyone without a bleeding disorder. I’m a spoiled clinician (not so much in my sickle cell clinic, but I’ve already written about that). With that as a baseline, what else could I want for my patients with bleeding disorders? I guess I’m a typical, hard-to-please millennial in that sense, finding myself still asking for more. Is it still entitlement if I want it for patients?
Generational stereotypes aside, there’s plenty to talk about in hemostasis this year, with two big themes I’ve noticed: 1) emerging non-factor therapies, and 2) large cohort data hoping to help guide management for patients with hemostatic disorders in tough situations (pregnancy, surgery, COVID, etc.). It’s Tuesday, folks, and with the meeting ending, I’m trying to summarize a little bit of everything and unfortunately had to leave some good stuff out.
On Sunday, we had a live Q&A hemophilia update (“Hemophilia Update: Our Cup Runneth Over”) that made for a good summary of these developing themes. Panelists Drs. Ming Yeong Lim, Alice Ma, and Lindsey George discussed optimal factor use, non-factor therapies, and gene therapy in hemophilia, respectively. If you missed it, watch the recording on the virtual meeting platform for an excellent overview of how this year’s plenary session and some other abstracts I will highlight fit into the larger conversation. The Monday Q&A for genetic testing in von Willebrand disease lived up to the hype (see my preview article) with fantastic discussion and great moderation from Dr. Robert Sidonio.
As we know from the plenary session (see my article detailing that in the Monday issue), fitusiran is making a big showing this year, and despite my gripes with outcomes, it will most certainly represent a paradigm shift for patients with hemophilia B. As a complement to the plenary abstract, which presented results from a phase III trial in patients with hemophilia A and B with inhibitors, we are going to have the late-breaking abstract, “Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia A or B Without Inhibitors (ATLAS-A/B)” presented today, Tuesday, December 14, at 9:00 a.m. Eastern time. Dr. Alok Srivistava will highlight data using fitusiran for patients with hemophilia A and B without inhibitors. I was again disappointed at the percentage of patients with no bleeds (50.6%) but very pleased to see no thrombotic events reported in this group, and quality-of-life metrics were likewise greatly improved.
As for advances in diagnosis and management, in a live Q&A on Monday, December 13, “Pregnancy in Special Populations: Challenges and Solutions,” a panel chaired by Dr. Marie Scully offered valuable guidance on managing von Willebrand disease (vWD) in pregnant women. This was a nice follow up to the Sunday session, “Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: New Insights on Hemostatic Challenges in Acquired and Inherited Bleeding Disorder,”, which featured two talks on the obstetric management of women with factor XI deficiency (abstract 495 by Dr. Shivani Handa) and maternal outcomes in vWD (abstract 494 by Dr. Bonnie Niu). Catch those on demand if you missed them.
In session 322 on “Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Bleeding Phenotypes in Inherited and Acquired Diseases, Interventions, and Complications,” data from Dr. Lauren Merz and colleagues brought much-needed attention to our “clotting bleeders” in a look at anticoagulant use and outcomes in patients with vWD and atrial fibrillation. These are hard groups to study, and findings like these are what lead to iterative improvements in complex management as our patients with hemostatic disorders age. The same session provided useful clinical observations from a large cohort of factor VII–deficient patients, as presented by Dr. Susan Halimeh. This bleeding disorder has a notoriously poor correlation with factor VII activity levels, and their data provide nice additional insight in management.
During oral abstract session 901 “Health Services Research–Non-Malignant Conditions: Optimizing Care in Thrombosis and Hemostasis,” held on Monday, December 13, a Canadian group led by Dr. Nisha Varughese presented interesting data in using pharmacokinetics in a standardized way within the care program to dramatically reduce costs for managing patients with hemophilia, making it a nice companion to the discussion by Dr. Lim in the hemophilia update live Q&A. As I’ve said before, factor isn’t going anywhere even with the new, non-factor kids on the block, so these data are a welcome addition to the hemostasis conversation.
I was privileged to speak in session 322 “Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Safety and Efficacy of Non-Factor Therapy in Hemophilia” on Sunday, December 12. It featured a fantastic group of abstracts regarding emicizumab use in non-severe hemophilia A (by Dr. Claude Négrier, and colleagues), surgical experience in patients with hemophilia A with inhibitors who are on emicizumab (by Dr. Giancarlo Castaman and colleagues), as well as real-world data in emicizumab outcomes (by Dr. Man-Chiu Poon and colleagues), showcasing its efficacy but ongoing difficulty in managing patients who are on the drug. The highlight of the session for me was the great phase II data about the use of concizumab (a tissue factor pathway inhibitor antibody) in surgical patients with hemophilia (by Dr. Allison Wheeler and colleagues), making this a good year for patients with hemophilia B.
In a world of plenty for the hemostasis community, how can we help but be spoiled? Our patients have safe, reliable options, with more on the way. We have great science to follow. With all this to be happy about, I almost feel bad complaining about inflation … but not quite.
Dr. Ellsworth indicated no relevant conflicts of interest.
