Katherine Regling, DO
Alexander Glaros, MD
When patients present for surgery, they have well-defined expectations of those involved. The surgeon performs the surgery. When patients bleed, the hematologist tells them why (“someone just cut you open”). A distant scientist identifies a treatment for that why (“don’t let someone cut you open next time”). To the average, non-medical professional the roles taken on in medicine may appear unbendable, with little room for overlap. In reality, medicine is a Venn diagram, with innumerable contact points between the work of basic scientists, clinical researchers, and the various clinical specialists involved for a given patient diagnosis. We all exist as individual components in a complex cascade not unlike the coagulation cascade. If we think of the patient as the broken endothelial surface, the surgeon becomes the platelet, rushing in to establish primary hemostasis. The hematology team is that collection of clotting factors supporting the surgeon in ensuring secondary hemostasis. The rest of the medical team bringing in factor XIII to cross-link the cascade, solidifies the overall health of the patient. And in the background, the scientists lyse the pieces, discovering why and how to empower all of them with the tools they need to perform at their best. One piece cannot truly succeed without the other, and no role is synonymous or restricted.
Dr. Shannon Meeks of Emory University chaired the fascinating Scientific Program session “Mechanisms and Modifiers of Bleeding” (Q&A available on demand), which demonstrated the importance of each of the aforementioned roles. “The session has so much diversity,” said Dr. Meeks, “looking at novel mechanisms that modify the coagulation system and how across many fields of medicine, these mechanisms and modifiers matter.”
The session dives into the history of resuscitation in trauma patients and its associated coagulopathy. Dr. Mitchell Cohen of the University of Colorado said, “The understanding of mechanisms across disease states has been revolutionized; it is beyond the bleeding and balancing of immune processes.” Dr. Cohen dissected the improvements in knowledge of the coagulation and inflammatory perturbations over the past few decades, and how this has led to translational methodologies to research not only trauma, but several other disease states including burns, cancer, and postpartum and peripartum hemorrhage.
Dr. Valerie O’Donnell of Cardiff University discussed the pivotal role of the phospholipid membrane surface of platelets and white blood cells with coagulation factors. With phospholipid oxidation of fatty acids, her lab has shown increased calcium localization, binding of clotting factors, and enhanced ability of phosphatidylserine to support coagulation. “They are an essential component to hemostasis, but when made at the wrong place at the wrong time they can contribute to thrombotic disease states,” said Dr. O’Donnell. Her lab has shown in mouse models that the lack of enzymatically oxidized phospholipids is protective against abdominal aortic aneurysms.
“My goal is to teach the viewers about the value of mathematical modeling and give clues and insights about what it is, what it can do, and how it may be useful as a hypothesis-generating tool,” said Dr. Karin Leiderman of the Colorado School of Mines. She leads the audience through how this computational approach has permitted studying of the variability of bleeding patterns amongst individuals with hemophilia A. Results of these computational studies identified how low-normal factor V activity enhances thrombin generation in hemophilia. When combined with high-normal prothrombin activity, thrombin generation was augmented further. Dr. Leiderman also highlights how the mathematical model allows researchers to retrospectively look at why the findings may be occurring and what the biochemical mechanism may be.
This year, an exhilarating common ground was found at the ASH annual meeting. Regardless of title, specialty, or scientific interest, this session on mechanisms and modifiers of bleeding had that “special something” to fully captivate each member of its audience, solidifying the dynamic roles and relationships each of us hold in the field of hematol”ogy and medicine overall. Each of us uniquely contributes to the Venn diagram in multiple areas and doing our part to unveil the missing pieces to the equation allows the patient to maintain their simple expectation — that whatever is broken is fixed.
Dr. Regling and Dr. Glaros indicated no relevant conflicts of interest.