In a recently published study in the New England Journal of Medicine, Mayo Clinic researchers Adam Kanack, Ph.D., Nelson Leung, M.D., and Anand Padmanabhan, M.B.B.S, Ph.D., have identified a novel subtype of a recently identified severe blood clotting disorder called monoclonal gammopathy of thrombotic significance (MGTS). This follows closely on the heels of the identification of the “index” (first) case in 2023 by Drs. Kanack and Padmanabhan, in a joint effort with the University of Michigan that was published in the journal Blood.

The new subtype of MGTS presents significant diagnostic challenges, with important implications for patient care. The discovery was made through the case study of a 62-year-old man who experienced multiple unprovoked blood clots over the previous six years, including clots in his legs and lungs, and a stroke. Despite anticoagulation therapy, the patient continued to develop blood clots, leading his Mayo Clinic physician, Dr. Leung, to further investigate his condition in collaboration with Dr. Padmanabhan’s group. Results showed that previously used standard tests for an MGTS diagnosis were entirely negative. Upon closer examination, it was found that the patient’s blood sample activated platelets only in the presence of a protein called platelet factor-4 (PF4), consistent with the presence of prothrombotic (clot-inducing) antibodies in the patient. Dr. Kanack, an associate Cconsultant in Dr. Padmanabhan’s group, devised a novel method to synthetically produce the harmful antibody, further confirming the diagnosis.

“It is so important to diagnose this condition because if you don’t have a diagnosis, you cannot come up with a treatment plan,” says Dr. Padmanabhan.

Dr. Leung adds, “The biggest research question in my mind related to MGTS is, how common is this? How many are we missing?”

Mayo Clinic has now followed several patients with MGTS across multiple countries since the publication of the index case.

“It appears pretty clear that we were missing these cases when they, in fact, existed,” added Dr. Padmanabhan.

The identification of MGTS allows for treatments that attack the plasma cells producing these harmful antibodies, as recently shown by Dr. Padmanabhan and colleagues at Stanford University in a separate paper in the New England Journal of Medicine. Future research aims to determine the prevalence of MGTS, identify potential triggers, and develop better diagnostic tools and treatments, which could help identify cases early and improve patient outcomes.

This discovery not only shines the spotlight on a previously unrecognized cause of blood clots, but opens new avenues for research, offering hope to patients with MGTS-driven clotting events.

“I think it’s important for us to keep learning from each other and educate ourselves about this new syndrome,” says Dr. Leung. “When my fellow physicians see a patient who may have some of the signs and symptoms of MGTS, it would be important for them to engage with the right expertise to explore this possibility because, if confirmed, it would open up important treatment possibilities.”

Mayo Clinic Laboratories is in the process of developing a test for MGTS. However, Mayo currently offers extensive and cost-effective testing for coagulation disorders, with 350,000 special coagulation tests performed annually.

Learn more in this paper published in the New England Journal of Medicine.