Young, energetic platelets start thrombosis, study indicates
Young blood platelets appear to be “first responders” to injuries in blood vessel walls, plugging the site of bleeding, while older platelets glom on as a blood clot begins to develop, according to new research out of the Health Science Center.
The research, funded by the National Heart, Lung, and Blood Institute, may have implications for the prevention of strokes caused by thrombosis (clot formation). It provides, for the first time, a picture of the process in zebrafish larvae. The Health Science Center scientists have repeated their finding in a mouse model.
Pudur Jagadeeswaran, Ph.D., professor of cellular and structural biology at the Health Science Center, and his co-authors found that young platelets appear to spur clots at the site of a blood vessel wound, whereas the more mature platelets appear to spread the clot formation further in the vessel. Platelets are thin disks of blood that have clotting properties.
Many strokes result from proliferation of platelets at the site of vessel lesions. About 700,000 Americans will have a stroke this year, one every 45 seconds, according to the American Stroke Association, a division of the American Heart Association.
“This is a novel finding that to our knowledge has not been shown in either zebrafish or mice,” said Dr. Jagadeeswaran, who joined the Health Science Center faculty in 1988. “It has implications for development of more effective anti-stroke therapies.”
The researchers, who have one of the largest collections of zebrafish in the United States, placed zebrafish larvae under a microscope and used a laser to cause blood vessel injury. They labeled young and old platelets with fluorescent dye to distinguish the activity of the two groups. “The younger platelets have more receptors (features on the surface that enable them to interact with external sources) and demonstrated more robust biological activity than the mature ones,” said Dr. Jagadeeswaran, who recently was invited to be the keynote speaker for the U.K.-Ireland Platelet Conference to be held in Dublin this September.
He noticed a mosaic pattern to resulting blood clots – clusters of younger and older platelets sort of woven together like a tapestry. “We believe this gives strength to the thrombus (clot),” he said.
Stroke often is treated with blood-thinning, anti-coagulant drugs – such as aspirin – that leave patients at higher risk for bleeding. Dr. Jagadeeswaran sees in his research the potential to design a drug to block only the young platelets from attaching to the site of vessel injury. “Aspirin blocks all the thrombotic activity indiscriminately,” he said. “If I can design an ‘anti-young-platelet drug,’ you would still have the old guys (mature platelets) plugging the site of bleeding, but not with as much vigor as the young guys.”
The zebrafish larvae findings will be reported in the July 1 print issue of Blood, the journal of the American Society of Hematology. They already are available online.