By Alvin H. Schmaier, MD, and Stanton L. Gerson, MD
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
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.
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