ASH Presentations Highlight Advances in Hematology Research

Several current research initiatives at Cleveland Clinic aim to answer critical questions about the origin and treatment of blood disorders. These initiatives will take center stage among the abstracts, posters and talks at the 56th Annual Meeting of the American Society of Hematology.

Below is a sample of the work to be presented at ASH, with insight from Keith McCrae, MD, hematologist at the Taussig Cancer Institute and researcher in the Department of Cellular and Molecular Medicine at the Lerner Research Institute.

A Novel Mechanism of Cellular Activation Mediated By Antiphospholipid Antibody-Induced Extracellular Vesicles

This project assessed an innovative mechanism by which endothelial-derived extracellular vesicles may contribute to Antiphospholipid Syndrome. When scientists incubated endothelial cells with antiphospholipid antibodies, the vesicles released by the activated cells were able to activate resting endothelial cells through a novel pathway involving vesicle-attached RNA. Endothelial cell activation renders the cells more prothrombotic.

“This provides us with new information about the nature of these vesicles,” Dr. McCrae says. “Everybody has circulating extracellular vesicles, but patients with antiphospholipid syndrome have greater numbers, and these results suggest that these vesicles also differ functionally from those in normal individuals.”

Findings will inform future research to better characterize and define how these vesicles differ in patients with the syndrome, hopefully shedding light on the disease’s pathogenesis.

Risk of Arterial and Venous Thrombosis in Patients with “Indeterminate” Lupus Anticoagulant Testing

What is the meaning of an uncertain test result? This project, also related to Antiphospholipid Syndrome, sought to answer that question by investigating Lupus anticoagulant, a subtype of antiphospholipid antibody that is most strongly associated with thrombosis.

One criterion for diagnosing Antiphospholipid Syndrome is a positive Lupus anticoagulant test. However, a large number of patients who are symptomatic for the syndrome test neither negative nor positive. This retrospective study examined patients with indeterminate results on the Lupus anticoagulant test to understand whether or not such test results are of any clinical significance.

“In our cohort, it appears that many patients with indeterminate Lupus anticoagulants still develop thrombosis. Moreover, in patients with other risk factors for thrombosis, such as factor V Leiden, thrombotic events are accentuated,” Dr. McCrae explains. “We still don’t know exactly what this means, but it suggests that an indeterminate Lupus anticoagulant test may still be meaningful and shouldn’t be simply ignored — particularly if the patient also has one of these other genetic risk factors.”

NADPH Oxidase Mediates Antiphospholipid Antibody-Induced Endothelial Cell Activation

A third study on Antiphospholipid Syndrome assessed the involvement of the NADPH oxidase enzyme complex in the activation of endothelial cells by antiphospholipid antibodies. The goal: to better understand the cellular signaling mechanisms triggered by the antiphospholipid antibodies during endothelial cell activation. Researchers discovered that, in endothelial cells, blocking the NADPH oxidase enzyme complex can greatly inhibit the ability of antiphospholipid antibodies to activate endothelial cells, thus preventing them from expressing prothrombotic activity.

These results suggest the potential therapeutic use of NADPH oxidase inhibitors for patients with antiphospholipid syndrome. Dr. McCrae considers such potential therapy beneficial as a possible alternative to the current standard of care—the life-long use of anticoagulant medications.

Increased Morbidity During Long Term Follow-up of Survivors of Thrombotic Thrombocytopenic Purpura

This follow-up study of thrombotic thrombocytopenic purpura clarifies the long-term effects of this rare but potentially fatal blood disorder — even after its successful treatment.

“The general idea in the past was, you treat it, and it’s over. But more and more evidence is suggesting that these patients have long-term complications,” explains Dr. McCrae, citing hypertension, stroke and depression as possible side effects. The study’s outcomes confirm that sequelae do occur and may be a target of intervention.

Presentation of these and other studies at the meeting will help underscore the need for better understanding of blood diseases, Dr. McCrae notes. In today’s austere funding environment, they also point to the need for advocates for greater research support.

“Hematology interfaces with and is an important component of many other diseases,” he says. “These presentations show that there’s a lot we still don’t know in hematology. There is a lot still to be done, and the answers to many, many questions remain unknown.”