Extending Platelet Storage

Extending the Life of Donated Platelets for Transfusions

About 2.2 million platelet doses are transfused annually in the U.S., most prophylactically to reduce the risk of spontaneous bleeding, but also in cases of trauma, burns, immunodeficiency diseases, autoimmune conditions, clotting disorders, and cancer. Unlike other blood components such as red blood cells and plasma, which can last refrigerated up to 42 days and frozen up to two years, platelets must be stored at room temperature, limiting the shelf life to about five days due to the risk of bacterial growth. In fact, sepsis from a bacterially contaminated platelet unit represents the most frequent infectious complication from any blood product today. Since the need for platelets continues to rise, maintaining sufficient clinical platelet inventories is difficult.

Biochemist Renhao Li, PhD, associate professor of pediatrics in hematology/oncology at the Emory Children's Center, was researching how transmembrane receptors on the platelet's surface transmit signals across the cell membrane. He stumbled upon a glycoprotein—Ib-IX-V complex—and started trying to understand how it worked and what it did. "GPIb-IX-V complex is the second most abundant receptor complex expressed on the platelet surface," Li says. "It is critically involved in many aspects of platelet physiology including its genesis, clearance and activation, and is a receptor for important ligands in the blood, such as von Willebrand factor, which affects blood clotting." He started studying how GPIb-IX-V "tells" platelets where to start clotting—how they "mark" the injury site under the force of the flowing blood.

A more complete understanding of these processes have the potential to lead to various therapeutic breakthroughs, especially if the signals can be controlled and used to combat illnesses from clotting disorders to cardiac disease.

But Li also made a side discovery: One subunit of GPIb-IX-V complex, called glycoprotein Ib-alpha (GP1BA), is continuously cleaved or shed from the platelet surface during platelet storage. The shedding is correlated with storage lesions, and some studies suggested that GP1BA shedding might lead to platelet clearance. "It takes two days to process donated platelets, making sure they are disease free—and now with Zika there's even more of a threat," he says. "So you have only three days left after that, which is often not enough time to get them to the people who need them. A high percentage of stored platelets go bad."

In fact, 16% of units become outdated or wasted, and each unit costs about $700. The important question, says Li, became: "Can we find a way to store them longer by slowing down GP1BA shedding?" So Li set about making an inhibitor, creating mouse monoclonal antibodies that bind a unique part of human GP1BA and inhibit its shedding and thus, platelet aging. He was able to pursue patent protection of these inhibitors with the help of Emory's Office of Technology Transfer (OTT), and began testing it in animal studies with Cassandra Josephson, MD, professor of pathology and pediatrics at Emory.

"This is the first of its kind. There is no other specific GP1BA shedding inhibitor in the world," he says. "Our tests suggest that it makes 8-day-old platelets behave like fresh ones." The antibody could be humanized and added to platelets in storage to increase their lifespan, which would reduce waste and save money and lives. "Even if the extension is only a moderate improvement, it's still extremely valuable," says Catherine Murari-Kanti, licensing associate in the Office of Technology Transfer. "He discovered this because he's looking at molecular mechanisms, platelet aging, and particular proteins—proving the very real value of basic science."

Techid: 13053

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