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Oscar Ratnoff, 91, Expert on Blood Clots, Is Dead




 

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 clotting.

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 internal plug.

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 and hemophilia.

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 until 2001.

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.



 


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