Dr. Oscar D. Ratnoff, whose insightful research into how the
blood coagulates helped reveal the "waterfall" biochemical
response involved in the body's reaction to wounds and trauma,
died on May 20 in Cleveland. He was 91.
The cause was respiratory failure, his family said.
In the late 1950s and early '60s, Dr. Ratnoff, a hematologist at
Case Western Reserve University, was able to isolate several of
the blood proteins involved in coagulation, known as factors, and
thereby helped unravel the biochemical sequence, called the
waterfall sequence or waterfall cascade, that leads to effective
Working with a biochemist, Earl W. Davie, Dr. Ratnoff studied a
blood sample that had failed to coagulate in a laboratory test
tube. The two scientists made comparisons with blood that
exhibited normal clotting and succeeded in isolating a plasma
protein, identified as Factor XII, lacking in the original
sample. In later experiments, they isolated two other proteins,
plasma thromboplastin antecedent (associated with Factor XI) and
Factor IX, and came up with an important hypothesis.
They proposed that proteins, lipids and calcium in the
bloodstream act upon one another in a 13-element sequence to help
construct a clot. In the process, they theorized, the proteins
are converted into enzymes and contribute to the production of
fibrin, an insoluble protein that is essential to coagulation.
Then, they conjectured, in order for the body to make a healthy
response to a wound, fibrin binds with blood cells to form an
Preliminary findings of Dr. Davie and Dr. Ratnoff were published
in the journal Biochemistry in 1962, and were then more fully
described in Science in 1964. Their results, along with related
work by the British scientist R. G. MacFarland, were a
groundbreaking step forward in the treatment of wounds, stroke
In the 1970s, before the advent of genetic testing, Dr. Ratnoff
helped devise a more accurate method for detecting carriers of
hemophilia, a hereditary blood-clotting disease that shows up in
men but is genetically transmitted by women. With a colleague at
Case Western, Dr. Theodore Zimmerman, Dr. Ratnoff adapted an
existing technique to use an antiserum derived from rabbits and
combine it with a blood factor. The test showed an accuracy level
of about 95 percent, a significant improvement from the roughly
25 percent accuracy of earlier tests.
In the 1980s, with the appearance of H.I.V., Dr. Ratnoff voiced
concerns about the vulnerability of hemophiliacs, most of whom
had been prescribed Factor VIII because they had congenital flaws
in their waterfall sequences. A portion of the Factor VIII
available commercially came from large-scale pooled blood
donations, in what Dr. Ratnoff considered to be a dangerous
avenue for the spread of hepatitis and AIDS. He observed that a
drop in lymphocyte counts among hemophiliac patients suggested an
increased susceptibility to blood-borne infections.
Dr. Nathan A. Berger, a professor of experimental medicine,
biochemistry and oncology at Case Western, and a former dean of
its medical school, said that Dr. Ratnoff's objections were
initially dismissed, because of the need to produce enough Factor
VIII for the marketplace.
"But ultimately," Dr. Berger said, "the medical community and the
drug companies came to see his point and favor a single-donor
approach. He was farsighted in that respect, and he had a voice
that had to be listened to."
In the 1990s, Dr. Ratnoff's argument became moot, as the Factor
VIII protein was cloned and genetically engineered for the first
time, eliminating the need for donated blood that might transmit
disease to those who needed Factor VIII.
The son of a prominent Brooklyn pediatrician, Oscar Davis Ratnoff
was born in Manhattan.
After receiving his medical degree from Columbia, he taught at
Harvard and Johns Hopkins. He joined Case Western in 1952, was
named a professor of medicine and remained active in his research
Dr. Ratnoff is survived by his wife of 63 years, Marian. The
couple lived in Cleveland Heights, Ohio. He is also survived by a
son, Dr. William Ratnoff, a rheumatologist, of Lubbock, Tex.; a
daughter, Martha Fleisher of Dallas; and five grandchildren.