July 2008 Ratnoff Headshot
Dr. Oscar D. Ratnoff was the consummate triple threat. He was an excellent clinician, basic and clinical researcher, and teacher and mentor. His 302 publications are filled with seminal observations that moved his field forward in the 1950s to the 1980s. His observations populated 29 Journal of Clinical Investigation and 63 Journal of Laboratory Clinical Medicine publications, many with trainees as first authors.
Dr. Ratnoff started his investigative career in liver disease, which introduced him to plasma proteins. At Johns Hopkins with Dr. Calvin Menzies, Dr. Ratnoff described a simple method to measure fibrinogen. In 1950, he moved to Cleveland and Case Western Reserve University (CWRU). In 1955, Dr. Ratnoff and Dr. Jane Colopy reported on a patient, John Hageman, who had reduced surface-activated blood coagulation times without bleeding. He and Dr. Earl Davie later identified, in 1961, the missing protein in the Hageman trait as factor XII and showed that it activated factor XI. This collaboration led directly to publication of the coagulation cascade hypothesis in 1964. They observed that isolated factor XII autoactivates on negatively charged surfaces leading to factor XI activation and then a waterfall of proteolytic reactions. At the time, the model synthesized the biochemical basis of blood coagulation and led to 44 years of refinements.
Dr. Ratnoff had a long-standing collaboration with Dr. Irwin Lepow, the discoverer of properdin in the complement system, and together they described the C1 inhibitor of the first components of the complement system. In 1969, Drs. Ratnoff and George Naff showed that the C1 inhibitor inhibits plasma kallikrein and plasmin, and, with Dr. Charles D. Forbes, described in 1970 that the C1 inhibitor also inhibits factor XIIa and factor XIa. In the 1970s, as part of an evaluation of a patient who had a long APTT without bleeding, but had normal factor XII, Drs. Ratnoff and Hidehiko Saito simultaneously, with the laboratories of Weupper, Colman, and Kaplan, described high-molecular-weight kininogen deficiency in humans.
Dr. Ratnoff's contributions to medicine were recognized by his election to the American Society for Clinical Investigation, the Association of American Physicians, and the National Academy of Sciences. He served as President of ASH and was selected to present the Henry M. Stratton Lecture in 1972. At CWRU and University Hospitals, he served as Division Chief of Hematology and Oncology and interim Chairman of the Department of Medicine. To his trainees, he was the skillful and talented editor, tireless reviewer, and constant scientific protagonist, but his greatest legacy is his influence on countless physicians, internists, and hematologists as the accomplished physician-scientist.
Dr. Ratnoff is survived by his wife, Marian Foreman Ratnoff, his daughter, Martha Ratnoff, and son, William Davis Ratnoff, MD.
For those who wish to donate, contributions may be made to the Dr. Oscar D. Ratnoff Research and Education Fund at the Case Western Reserve University School of Medicine.
Dr. Ratnoff was profiled in the January/February 2008 issue of The Hematologist as part of ASH's ongoing series for the 50th anniversary.
