Freeze-Dried Platelets

East Carolina University Pathology professor Arthur P. Bode can hold the symbol of $10 million and 12 years of painstaking research in the palm of his hand: a vial of white powder that looks no more glamorous than Epsom salts. But, a few years from now, in the hands of an Army medic on the battlefield, a paramedic at an accident scene or a surgeon in an operating room, that little vial could save a life.

Or many lives. Dubbed StasiX™, the powder consists of human blood platelets freeze-dried and sterilized though a process Bode developed with collaborators at UNC-Chapel Hill. In laboratory and animal tests, the freeze-dried platelets have shown the ability to quickly stop bleeding in cases of severe injury. Best of all, they can be stored safely at room temperature up to five years — compared with a limit of five days on blood bank platelets — making them practical for situations beyond the reach of traditional blood banks. These properties represent the potential to save the lives of thousands of people worldwide who bleed to death each year.

To turn that potential into reality, Bode and his partners have formed Hemocellular Therapeutics Inc., a private company that has licensed the technology from the universities and secured about $1 million in private seed capital to refine the freeze-drying process further. Within the next few months, they plan to submit to the U.S. Food and Drug Administration a proposal to begin clinical trials in humans. If all goes according to plan, freeze-dried platelets could be in widespread use within the next few years.

For the military, freeze-dried platelets represented the potential to keep soldiers and sailors from bleeding to death in the midst of battle. Platelets have several properties, the most critical being their role as the body’s first-responder to injury. When they sense a wound, they stick to it and promote clotting. Without platelets, chances of stopping severe bleeding are slim. Yet platelets have been missing in action from the battlefront.

Currently, blood is separated into three products for blood banking. Plasma, the fluid part, can be freeze-dried and stored for years. Red cells, which carry oxygen, can be kept refrigerated for seven weeks. Refrigerated platelets, on the other hand, refuse to recirculate. At room temperature, the short shelf life of platelets renders them useless for military field operations. Civilian blood banks also run into problems. Occasionally, they run short, but overall, they discard about 20 percent of platelets, unused, when they pass the expiration date. Clearly, freeze-dried platelets — easy to store and transport — would be a major benefit.

Previous attempts to produce freeze-dried platelets for transfusion date back to the 1950s. None succeeded. In 1989, with funding from the Navy, Bode at ECU and Dr. Marjorie Read at UNC-CH took on the challenge. One after another, they tried different fixatives and treatments — microwaving, air-drying, freeze-drying, a lot of “kitchen chemistry,” as Bode described it. “It took about four years to get to where we could, very nicely, with fine tuning, get the platelets fixed so that we rigidified their surface no more than you had to, to be able to freeze-dry them and still have a fairly active cell once you added the water back.”

Eventually, tests would show that freeze-drying, or lyophilization, not only preserves the platelets’ clotting properties, but enhances them. When transfused, blood bank platelets can take up to 24 hours to regain full function. Freeze-dried platelets, reconstituted in a saline solution, instantly go to work to stop bleeding.

The process is amazingly simple. “There’s nothing fancy about it,” Bode said. “Just take a bottle [of freeze-dried platelets], shoot it into the salt solution, and swirl, swirl, swirl. It bursts back into cells.” With that burst, the reconstituted platelets are ready for a bleeding patient.

So far, the platelets have shown no deterioration from being stored up to five years. The only apparent use for which blood bank platelets remain superior is as preventative therapy. Blood bank platelets are preferable if the goal is to fortify a patient’s blood to prevent bleeding; but if the patient is already bleeding, freeze-dried platelets promise a better solution.

As Hemocellular has gotten off the ground, federal funders have renewed their interest. The Office of Naval Research recently awarded Bode a $270,000 grant to help refine the process so it can meet FDA requirements and be scaled up to produce quantities necessary for clinical trials. Still, significant challenges lie ahead. Eventually, Hemocellular will need at least $5 million in financing to complete the first phase of clinical trials and 10 times that to be ready to produce the first commercial vial of StasiX™. So far, fund-raising has been hampered by a slow economy.

The team also must prove the technology for medical use. Freeze-dried platelets must be shown to be both safe and effective in humans.

The first clinical trials, Bode said, will likely involve open-heart surgery. “Open-heart surgery patients bleed a lot,” he said. “About 15 percent will bleed to the point where they’re in danger of bleeding to death. We think that if you infused our products, you’d stop the blood loss and avoid shock. [Patients] will get off the table sooner and recover faster. There’ll be less stress on the body.”

Because open-heart procedures are so carefully controlled, he said, they will provide an ideal test. The potential uses are far broader. Every year some 4 million hospital admissions involve hemorrhaging, and 50,000 people bleed to death, according to the Centers for Disease Control. That’s just in the United States. Worldwide, 110,000 women will bleed to death every year in childbirth alone. Of all the potential uses, however, never far from Bode’s mind is the dire need that first launched the research.

“We want to get into the trauma market,” he said. “Will we be able to stop death from exsanguination on the battlefield? Right now, they can only put in plasma, which will increase blood pressure and cause further bleeding. It keeps the brain alive, but you bleed out. Put in our stuff, and you save a life.”

That little vial of white powder begins to look pretty big.