Blood clots can help or hurt, depending on where they occur. When you get a cut, platelets swarm to the site of an injury and join together, forming a clot that stops the bleeding. But for individuals with the disease atherosclerosis, injury occurs within the wall of an artery and fatty tissue builds up inside these walls and eventually bursts. When platelets swarm to this injury site, the resulting clot can block the flow of blood. Blockage in the coronary artery can cause thrombosis and a heart attack.
The dual nature of blood clots has also been part of a standing mystery: Clots can squeeze in on themselves, becoming denser and tougher, but they don’t seem to do this when closing a wound. Now, a team of researchers from the Engineering School has uncovered the reason why—clots are able to sense the flow of blood around them.
“Researchers have known for decades that blood sitting in a test tube will clot and then contract to squeeze out water,” says Ryan Muthard, a graduate student in the Department of Chemical and Biomolecular Engineering. “Yet clots observed inside injured mouse blood vessels don’t display much contractile activity. We never knew how to reconcile these two studies, until an unexpected observation in the lab.”
Muthard and Scott Diamond, professor and chair of Chemical and Biomolecular Engineering, say they were using a specially designed microfluidic device to study the bleeding-blocking properties of blood clots. When they stopped the flow to add a fluorescent dye, they were startled to see that a massive contraction was triggered in the clot. When they delivered the dye without stopping the flow, there was no change in the clot’s properties.
“We think this may be one of the fundamental differences between clots formed inside blood vessels that cause thrombosis and clots formed when blood slowly pools around a leaking blood vessel during a bleeding event,” Diamond says. “The flow sensing alters the clot mechanics.”
The researchers believe that blood flow normally washes away some of the chemicals that activate platelets, so when blood flow is blocked, those chemicals build up and cause the clot to contract. By adding drugs that block these chemicals, the researchers were able to prevent the contraction. Millions of patients already take drugs, such as Plavix and aspirin, which target these chemical pathways.
A better understanding of the clotting dynamics that occur in atherosclerosis, as opposed to the dynamics at play in closing a wound, could lead to more effective drugs for heart attack prevention.
Originally published on November 1, 2012