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Dare to Think Outside the Box: A Celebration of Platelets, Passion, and Perseverance

December 10, 2023
Hilary Whitworth, MD, MSCE, (@HilaryWhitworth)
Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, PA

This year’s Ham-Wasserman Lecture was the capstone to a long, successful, and meaningful career by Andreas Greinacher, MD, who will retire from clinical medicine shortly after the 2023 ASH Annual Meeting. Dr. Greinacher is a professor of transfusion medicine at the University of Greifswald in Germany, with a wide range of expertise including transfusion medicine, immunohematology, thrombosis, and hemostasis. His Ham-Wasserman Lecture yesterday focused on one of his first passions — platelets and anti-platelet factor 4 (PF4) related disorders. Heparin induced thrombocytopenia (HIT) is the classic anti-PF4 disorder, where IgG antibodies bind to heparin PF4 complexes, leading to platelet activation and thrombosis with the potential to precipitate devastating consequences if left unrecognized. Anti-PF4 disorders had a recent resurgence of fame thanks to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare adverse event associated with adenovirus-based COVID-19 vaccines due to heparin independent platelet activation by anti-PF4 antibodies.  

I had the distinct pleasure of talking with Dr. Greinacher about his career as I prepared for this article. He told the story of his initial interest in platelets which began as a medical student in Germany, caring for a woman about to have a splenectomy to treat presumed immune thrombocytopenia (ITP). After reviewing the blood smear, Dr. Greinacher was not convinced by the ITP diagnosis. He went on a quest that medical students today could not even fathom — including a trip to the library where he read a paper describing a similar clinical scenario and mailing a letter to that author, Jim White, MD, a professor at the University of Minnesota who has since passed. In a world without internet literature searches, email, or video calls, a tenacious Dr. Greinacher cobbled together reagents and sent Dr. White a sample, which confirmed the diagnosis of Sebastian syndrome (now part of the MYH9-related disorders) and led to Dr. Greinacher’s first publication. This experience taught him to question whether what he is told is correct and demonstrated the importance of mentorship. He now teaches his trainees the same, encouraging them “to dare to use their capacities to think outside the box.”  

Dr. Greinacher’s interest in anti-PF4 related disorders also developed as a trainee, when he cared for a patient with thrombosis and thrombocytopenia after orthopedic surgery who was treated with heparin, and unfortunately died shortly after. He began to develop diagnostic tests and study alternative anticoagulants to treat these patients, leading to a long and productive research career with enormous clinical impact. His prior work on anti-PF4 disorders prepared him and his colleagues to quickly recognize and investigate VITT. He shared with me a remarkable timeline from March 2021, starting with a phone call on March 14 reporting the first VITT patient in Vienna, followed by a German guidance paper published just three days later, and a submission to the New England Journal of Medicine on March 20. They were able to leverage their prior work and experimental designs from HIT to study VITT. “It was like condensing 30 years of research into three weeks,” he shared. VITT brought broad recognition of the importance of anti-PF4 disorders, which continues to provoke important questions Dr. Greinacher hopes to answer, such as whether unrecognized anti-PF4 antibodies are implicated in other populations with thrombosis. 

What’s next after he retires from his clinical obligations? He said he will continue some of his research and focus on activities that keep him motivated. These include a long-standing passion for international initiatives, such as working with colleagues in Nigeria to organize safe blood services. (Read more about this project and the collaboration between Dr. Greinacher and Dr. Angela Ugwu through the ASH Visitor Training Program in this ASH Clinical News article).  

His impressive career is marked by numerous high-impact papers, awards, and accolades. However, he told me that while the accomplishments are nice, “Nothing tastes as flat as the success of yesterday.” Rather, he highlighted the ongoing interactions with colleagues from all over the world as one of the most rewarding parts of his career. These relationships and collaborations, many of which he developed at annual meetings such as ASH, have been the maintaining force in his career.  

Dr. Greinacher ended our virtual meeting by telling me he will pack up his office when he gets back from ASH. However, only one of his many awards hangs in his office given to him in 2021 for teaching the best academic course — a medical student pharmacology course on anticoagulants. He took the plaque off the wall and brought it closer to the camera to show me, telling me the most important job of a clinician-scientist is to teach the next generation. When I asked him what advice he would give someone in their early career, he replied, “Do what you feel is important, and do it right.”  

The Ham-Wasserman Lecture told the story of anti-PF4 disorders from HIT to VITT, but this is just one part of Dr. Greinacher’s remarkable career. It was a privilege to meet him, and I hope others are as inspired by his passion and perseverance as I am.  

Dr. Whitworth indicated no relevant conflicts of interest. 

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