Dr. Minoru Okuma, who acted as President of the 59th Congress of the Japanese Society of Hematology, as Chairman of the Board of Directors of the Japanese Society of Hematology, and as an honorary member of the Japanese Society on Thrombosis and Hemostasis, passed away at the age of 90 on January 17, 2024. Here I would like to look back upon his achievements with deep respect and gratitude for his contributions to progress in hematology, especially in the area of thrombosis and hemostasis.

Born in 1933, Dr. Okuma graduated from the Faculty of Medicine, University of Kyoto in 1958. Shortly after graduation, he joined the 1st Department of Internal Medicine, chaired by Professor Gyouiti Wakisaka, Kyoto University, where he began his professional career in medical sciences under Dr. Kohjiro Yasunaga (later, Professor of Kansai Medical University) following his clinical training. In 1968, he joined Professor Mario Baldini’s laboratory at Brown University in Providence, R.I., U.S.A. to study platelet storage as a post-doctoral fellow. In this laboratory, he was assigned to research lipid content and changes during platelet storage. He ended up studying changes in malondialdehyde as an indicator of lipid peroxidation during platelet storage, and found that malondialdehyde formation increased in thrombin-stimulated platelets. Notably, at that time, it was not known that malondialdehyde increased as an arachidonate metabolite (also including thromboxane A2) in activated platelets until Dr. Bengt Samuelsson (a Nobel prize laureate) uncovered the details of arachidonate metabolism via both cyclooxygenase and 12-lipoxygenase in human platelets. After finishing his post-doctoral fellowship, Dr. Okuma returned to Kitano Hospital in Osaka, Japan. While working there as a hematological clinician, he also continued to study the glycerophosphate pathway in platelets late into the night almost every day at the Department of Medical Chemistry, Kyoto University, chaired by Professor Shosaku Numa, who was strongly impressed by Dr. Okuma’s hard-working research attitude. Due to these achievements and Professor Numa’s strong recommendation, in 1974, Dr. Okuma became an assistant professor of the 1st Department of Internal Medicine, chaired by Professor Haruto Uchino. Needless to say, Internal Medicine during this period was not yet as narrowly specialized as it is today, but was divided into three large departments. The 1st Department of Internal Medicine consisted of two divisions: Gastroenterology and Hematology. Both divisions at that time were further differentiated into several subgroups, each having its own laboratory. The Hematology division included the Leukemia Laboratory led by Dr. Toru Nakamura (later, Professor at Fukui Medical School), the Lymphoma Laboratory by Dr. Shigeru Shirakawa (later, Professor at Mie University), and the Immunology Laboratory by Dr. Kiyoshi Takatsuki (later, Professor at Kumamoto University), among others.

Dr. Okuma was mainly responsible for the clinical area of thrombosis and hemostasis until he was appointed Professor and Chairman of the 1st Department of Internal Medicine in 1990. He aimed to discover novel platelet function disorders, especially ones related to arachidonate metabolism. In retrospect, his idea was prescient and timely considering that arachidonate metabolism in platelets was a newly developing research area, and platelet aggregometry became available worldwide. Dr. Okuma established his own rigorous and sensitive method for evaluating platelet function and arachidonate metabolism, and soon discovered 12-lipoxygenase deficiency in platelets obtained from patients with myeloproliferative disorders (now called myeloproliferative neoplasms). Importantly, in his laboratory, these platelet function studies were performed almost every day for all the patients Dr. Okuma met at Kyoto University Hospital. His move into these routine studies was greatly aided by young graduate students such as K. Kanaji, T. Sugiyama, F. Ushikubi, T. Ishibashi, S. Sensaki, K. Tomo, and myself. Notably, this patient and meticulous work, passed down from one to another, resulted in the important discovery of two platelet dysfunctions among thousands of tested patients.

Dr. Ushikubi (later, Professor at the Department of Pharmacology, Asahikawa Medical University) found thromboxane A2-unresponsive platelets suspected to have a receptor abnormality. This finding motivated him to purify the human thromboxane A2 receptor, leading to achievement of its molecular cloning in Professor Narumiya’s laboratory at the Department of Pharmacology, Kyoto University.

Dr. Sugiyama found glycoprotein VI (GPVI) deficient collagen-unresponsive platelets and anti-GPVI autoantibodies in patient plasma. This discovery constituted a breakthrough in understanding platelet-activating collagen receptor, which was previously a mystery in platelet biology. Generous gifts of these anti-GPVI autoantibodies in response to requests from many laboratories worldwide greatly contributed to progress in understanding the previously unknown platelet-activating collagen receptor now defined as the immunoreceptor GPVI/Fc receptor γ-chain complex.

You might wonder why these remarkable original discoveries were achieved in Dr. Okuma’s laboratory, which was a small clinical laboratory not as well-equipped as basic medicine laboratories. The answer might lie in what I mentioned above: the rigorous and sensitive platelet function studies established by Dr. Okuma were performed almost every day for thousands of patients, even though the results often seemed insignificant or disappointing.

I remember Professor Mario Boldini saying that Dr. Okuma was his favorite of the many Japanese post-doctoral fellows who came to his laboratory because Dr. Okuma was an extremely keen and hard-working researcher, earning him the nickname “Iron Man.”

Professor Okuma dedicated himself wholeheartedly to progress in all aspects of his laboratory, and medical research in the 1st Department of Internal Medicine at Kyoto University. We will deeply miss him and his extraordinary dedication to research in the field of platelet biology and dysfunctions.