Angela Weyand, MD
I’m with Dr. Alice Ma on this one. Classical hematology, or the study of nonmalignant, but not so “benign,” hematologic conditions evokes an image of white bearded, Latin speaking, tweed blazer (with elbow patches) wearing physicians, gathering in dusty, musty libraries. But based on all the exciting sessions at the 2020 ASH Annual Meeting, it is clear that classical hematology is anything but stodgy.
Over the past three decades, the care of patients with hemophilia has evolved from sole reliance on plasma derived therapies to the development of non-factor products and the promise of gene therapy. Though plasma derived therapies held great promise, they also carried enormous consequences. And no one knows this better than author and activist Dr. Robert Massie, who was born with severe hemophilia and acquired HIV and hepatitis C through factor therapy. In the Blood and Beyond session “Medical Mistakes and Miracles: Surviving Hemophilia, HIV and Hepatitis C” (available on demand). Dr. Massie presents a compelling story of medical error ultimately ending in redemption. From missing out on Halloween due to a joint bleed, calling for senate hearings on plasma factor products, and undergoing the liver transplant that cured him, Dr. Massie weaves a touching tale, infused with humor, hope, and inspiration. Transfusion-transmitted diseases created an exigent push for new technologies, and factor replacement therapy now is incredibly safe.
Yet challenges in the treatment of hemophilia remain, and these challenges led to the development of non-factor products such as emicizumab, a bispecific antibody that acts as a FVIII mimetic. Emicizumab has revolutionized the care of patients with FVIII inhibitors but its role in the treatment of patients without inhibitors is not without controversy. Dr. Guy Young and Dr. Robert Sidonio debate the role of emicizumab in the Spotlight Session “Emicizumab’s Impact on the Landscape of Hemophilia A Treatment: Two Artists Debate the View” (available on demand). Although the topic is blood, thankfully none is shed. Whether you are a factor fanatic or an emicizumab extremist, this is a lively discussion, one that touches on use in previously untreated patients; concomitant factor VIII and emicizumab; the role of inhibitor tolerance induction; periprocedural management; and use in non-severe, older, and highly active patients. Even more exciting than nonfactor products, the dream of gene therapy for hemophilia is finally becoming a reality. Catch the on-demand recording of the Late Breaking Abstract session where Dr. Steven Pipe presents phase III data on the uniQure Hemophilia B program, the largest hemophilia gene therapy cohort to date, demonstrating achievement of near-normal levels of FIX, despite 42 percent of patients entering the trial with pre-existing antibodies. Patients were able to discontinue prophylaxis, with bleeding largely abolished in the 26-week follow-up, and with a similar safety profile to that seen in earlier phases.
I think we can all agree that those results are amazing. But if you’re looking for more debate, look no further than the Education Program session “What Hematologists Need to Know About Giving and Stopping Aspirin” (available on demand). For such a tiny little pill, aspirin sure does incite a lot of strong opinions. For years, many older adults lived by “an aspirin a day keeps the interventional cardiologist away” but more recent studies have led to changing guidelines. Dr. Erin Michos discusses patient selection for those who may benefit from daily aspirin, the factors that weigh into this decision, and how to engage in clinician-patient risk discussion. For primary prevention, the overall risk of cardiac events is quite low and bleeding risk must be considered. The best advice on aspirin in healthy people? “Take one aspirin a day. Take it out for a jog, take it to the gym, then for a bike ride.” Dr. Geoffrey Barnes discusses the hemostasis nightmare of dual antithrombotic and antiplatelet therapy, clearly breaking down a complicated topic. With huge numbers of patients affected by atrial fibrillation, where anticoagulation is recommended, and by coronary artery disease, where antiplatelet is indicated, a lack of data means that things could quickly turn into a bloody mess! As Dr. Barnes so eloquently states “Sometimes more is more. Sometimes less is more. We review when to use more meds and when to use fewer!” Finally, although we typically think of aspirin with regard to arterial events, Dr. David Garcia considers whether “an aspirin a day keeps the SCDs* away” in discussing the possible role of antiplatelet therapy in preventing both primary and secondary venous thrombosis. Although there are data that aspirin has an effect in primary prevention, it should only be rarely used in secondary prevention. Further questions remain with regard to comparative efficacy with anticoagulation and the extent that bleeding risk is decreased.
Although unlikely to provide as much benefit as aspirin, it turns out that an apple a day (or at least how it affects your gut microbiome) may also impact your thrombosis risk. These days, commensal microbiota are increasingly recognized to be involved in numerous disease states. Dr. Martin Kriegel presents the role of the microbiome in the scariest of non-benign hematologic conditions, antiphospholipid syndrome, in the Scientific Program session “Gut Microbiome and the Endothelium” (available on demand). Not to be outdone, Dr. Mark Kahn blows our minds by presenting a gut-brain (!) disease axis and its implications for vascular malformations and stroke. Lastly, Dr. Weifei Zhu discusses mechanistic links between a western diet, platelet hyperresponsiveness, and cardiovascular disease and how this contributes to stroke risk susceptibility. I suggest gathering some healthy snacks for that one.
Clearly what we put in our bodies is important, and nutritional deficiencies have many hematologic consequences. Iron deficiency (ID), the most common nutritional deficiency in the world, is incredibly common in pregnancy (with 77% of North American pregnant women affected) and is associated with poor maternal and fetal outcomes. Dr. Jennifer Teichman presents on this important topic in the oral session “Suboptimal Iron Deficiency Screening in Pregnant Women in a High Resource Setting.” (This was also spotlighted in Dr. Alisa Wolberg’s roundup of nonmalignant themes in the Best of ASH session.) In a study of more than 47,000 (!) pregnancies, less than 60 percent of patients had ferritin levels evaluated; of those, more than half had ID, with almost a quarter being severely affected. Although only 8.3 percent of the women were anemic, only 27 percent had ferritin evaluated following the anemia diagnosis. Despite the fact that iron deficiency is associated with lower socioeconomic status (SES), the authors found that lower SES status was associated with reduced odds of screening. I applaud the authors in advocating for universal screening to address this important health equity issue.
Whether you call it classical, nonmalignant somewhat-benign (copyright Dr. Ma), complex (copyright Dr. Sholzberg), or just reclaim “hematology” alone (the others can have “oncology”), there is lots of work to be done and so much fun to be had!
Dr. Weyand indicated no relevant conflicts of interest.
*Sequential compression devices