Patients undergoing complex cardiac surgery are at risk of excessive bleeding, a life-threatening complication that can occur during or after the operation and often requires a transfusion of platelets. Platelets help blood clot, preventing blood loss.
The Food and Drug Administration allows hospitals to store platelets at room temperature for only five to seven days. But there is renewed interest in reviving a practice common before 1970: using platelets stored at cold temperatures, particularly in people experiencing trauma or massive bleeding. Small studies have suggested that cold platelets may be more effective at helping blood clot. Currently, however, cold platelets can only be stored for three days, which makes it difficult for hospitals to keep supplies stocked. Recent data have shown that cold platelets stored for up to 21 days may improve clotting function compared with room-temperature platelets stored for up to 5 to 7 days.
A large, multicenter study led by researchers at Washington University School of Medicine in St. Louis and the University of Minnesota Medical School in Minneapolis seeks to definitively determine whether maintaining platelets in cold storage is as effective in reducing blood loss as platelets stored at room temperature and whether the shelf life of cold platelets can be safely extended to 21 days, which could boost availability of platelets for patients experiencing major blood loss.
The research will be funded by the Department of Defense via a $26 million, five-year contract. The effort will include a phase 3 multicenter, double-blinded trial of 1,000 adult and pediatric patients who are undergoing complex cardiac surgery and will require platelet infusions that are given to patients who are actively bleeding. Up to 20 hospitals will participate in the research, scheduled to begin in the summer, with the potential to include additional sites in Canada, Australia and the United Kingdom.
The defense department’s primary interest in the research is to improve outcomes for bleeding patients by licensing a product that is more effective at making blood clots and has improved availability. The longer shelf life will allow wider distribution to remote medical teams, and may improve treatment for bleeding soldiers injured in combat and austere settings in the U.S. Civilians also stand to benefit from the research. In the U.S., nearly 7,000 units of platelets are needed each day, and supplies often are limited, according to the American Red Cross.
“Platelets are essential for saving the lives of patients with severe bleeding,” said the study’s co-principal investigator, Philip C. Spinella, MD, a director of the Pediatric Critical Care Translational Research Program and a professor of pediatrics at Washington University. “If we find a clotting benefit from cold storage, the findings from this trial with cardiac surgery patients also may be applied to patients who experience life-threatening excessive bleeding from other causes of severe bleeding such as traumatic injury, gastrointestinal problems or childbirth.”
Cold storage of platelets fell out of favor decades ago, when the blood banking community preferred to have a single storage temperature for platelet products instead of maintaining a dual inventory, with cold platelets used for actively bleeding patients and room-temperature platelets used to prevent bleeding in cancer patients with low platelet counts.
However, recent studies have indicated that the use of platelets stored at 4 degrees Celsius (39 degrees Fahrenheit) may be more effective at forming clots and preventing excessive bleeding than platelets stored at room temperature, which is 22 degrees Celsius (68 degrees Fahrenheit). Studies also have shown that storing platelets in cold temperatures helps to reduce the platelet’s cellular metabolism, maintain their ability to clot, and limit bacterial growth that may cause infections. Platelets stored at room temperature expend energy more quickly and, as a result, may struggle to form clots.
“If the study indicates that cold platelets can be stored longer, this will increase the availability of platelets for patients with excessive bleeding,” said Spinella, who treats patients at St. Louis Children’s Hospital. “Platelets are unavailable at many hospitals in suburban and rural areas due to the five-to-seven-day shelf life. Extending storage time with platelets that have superior clotting function has the potential to save many lives at hospitals that cannot keep platelets in inventory because of the short shelf life.”
Patients in the study will be randomly assigned to receive platelets stored at 4 degrees C or at room temperature before their surgeries. During the course of the study, the researchers plan to slowly increase the storage duration of cold platelets from seven days to a maximum of 21 days; however, they will stop if a longer duration proves ineffective at controlling bleeding. “There are transfusion reaction risks when using room-temperature platelets and cold-storage platelets, and we will monitor each patient closely,” Spinella said.
The study’s other co-investigators include the University of Minnesota’s Marie E. Steiner, MD, a professor of pediatrics, and Nicole D. Zantek, MD, PhD, an associate professor in laboratory medicine and pathology.
The contract also includes a parallel laboratory-based study that will be led by Susan Shea, PhD, a researcher in pediatric critical care medicine and who works in Spinella’s lab. This study will examine platelet function for cold and room-temperature platelets and the different ways those platelets may be collected and stored. The FDA needs such data when deciding whether to approve the licensing of cold platelets.
This project involves collaboration between the School of Medicine and the U.S. Army Institute of Surgical Research. The U.S. Army Medical Materiel Development Activity, a medical products development program, is providing funding to Washington University to conduct the trial.