Blood clot agent's genes are read.

Blood clot agent's genes are read

The protein responsible for triggering blood clots in the body has been cloned and its genetic code cracked, researchers report. The new information, they say, could eventually lead to the development of a new class of anticlotting drugs to combat heart attacks and strokes.

The protein, called tissue factor, is one of eight major proteins involved in coagulation. But unlike the other clotting proteins, which circulate in the blood, tissue factor is bound to cell membranes within blood vessel linings. Because of the difficulties in working with such membrane-bound proteins, and because the protein is present in extremely minute quantities, tissue factor did not succumb easily to genetic analysis.

"It took a long time to convince people that it even existed,' Ronald Bach, one of the researchers, told SCIENCE NEWS. "This is not just an accelerator, but the initiator' of the clotting process, he says. And not surprisingly, he notes, the amino acid sequence of tissue factor is remarkably different from other clotting factors--evidence that tissue factor has separate evolutionary roots. Whereas other clotting factors rely upon proteolytic activation by blood-borne enzymes, tissue factor triggers coagulation in response to tissue damage. It is the last of the blood clotting proteins to have its genetic sequence completely deduced.

The research, published in the August PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.84, No.15), was a collaborative effort by scientists at Yale University in New Haven, Conn., and the Mount Sinai School of Medicine in New York City. According to Bach, who was part of the Mount Sinai team, the work could lead to the development of antibodies or assays to measure tissue factor availability. Such tests might detect early signs of thrombosis--the blocking of blood vessels due to unwanted clots--so as to allow early intervention with clot-dissolving drugs. The research could also facilitate the discovery of natural clot inhibitors capable of blocking coagulation before it even begins.

Such inhibitory mechanisms are sure to exist, Bach says. "A microgram of this protein--one-millionth of a gram--is enough to clot all the blood in your body in about 25 seconds. This tells you that it must be very tightly controlled.'