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Hematology

Army Research Challenges Long-Standing Platelet Storage Recommendations

by Annette Boyle

February 1, 2019

SAN ANTONIO–For nearly 50 years, platelets have been stored at room temperature. Research conducted by investigators at the U.S. Army Institute of Surgical Research Center in San Antonio very well could change that.

Their study presented at the recent American Society of Hematology 2018 annual meeting calls into question the long-standing practice.1

In 1969, a study published in the New England Journal of Medicine concluded that “the use of cold temperatures should be abandoned in the preparation and storage of platelets for transfusion purposes” based on “rapid loss of viability as measured by poor recovery and shortened life-span in the recipient.”2

Today, platelets are stored in incubators that maintain a temperature of 20 oC to 24oC and provide continuous, gentle agitation. Because room temperature storage increases the risk of bacterial contamination, platelets can only be held for five days in most instances. Use of a special testing protocol and equipment approved by the U.S. Food and Drug Administration can extend storage to seven days.

The short storage time leads to significant waste. “Refrigeration of platelets would allow for all blood products to be kept at the same temperature and has the potential to significantly extend platelet shelf life to at least 14 days,” said Kristin Reddoch-Cardenas, PhD, staff scientist, Coagulation and Blood Research Program, U.S. Army Institute of Surgical Research Center–Cherokee Nation Technology Solutions.

In addition, “refrigeration minimizes the risk of bacterial contamination (and the subsequent risk of transfusion-associated reactions like sepsis and transfusion-related acute lung injury),” Reddoch-Cardenas told U.S. Medicine. While platelets are typically tested for bacterial contamination at collection, the testing methods can take up to seven days to detect contamination, according to the authors of the ASH study.

To assess the difference in bacterial growth in refrigerated versus room temperature platelets, the Army researchers inoculated both fresh plasma and apheresis platelets in plasma with Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis or placebo. The room temperature samples were gently agitated as customary; the refrigerated samples were not.

They found that the room temperature platelet samples should rapid bacterial growth over the first four days, while none of the refrigerated samples had detectable growth through Day 5. Refrigeration seemed to preserve platelet function and minimize activation, regardless of bacterial contamination. Room temperature storage, in contrast, led to markedly reduced platelet aggregation made worse by bacterial contamination.

The researchers concluded that “bacterial growth can be controlled through refrigeration without loss of function and [room temperature] storage may potentiate growth of certain bacterial strains through accelerated [platelet] metabolism.”

Effectiveness of Refrigerated Platelets

But do refrigerated platelets work as well as platelets stored at room temperature? The 1969 NEJM article and subsequent move to refrigeration assumed that hemostatic function and survival in circulation were both necessary for effective transfusion.3

“Accelerated platelet clearance is a well-known outcome of platelet refrigeration,” noted Reddoch-Cardenas. Research over the past 15 years by Karin Hoffmeister, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston and colleagues have demonstrated that platelet clearance and hemostatic function may be independent.

Further, the desialylation of platelet glycoproteins that lead hepatic macrophages to target platelets for removal could be reduced by the addition of sialidase inhibitors, Reddoch-Cardenas noted, “but it is currently unclear what effect this action has on platelet hemostatic function.”

Rapid clearance may not reduce the benefit of refrigerated platelets, however. “Despite a very short circulation time and accelerated clearance, refrigerated platelets have been shown to participate in clot formation at the site of injury in a rat model of polytrauma and hemorrhagic shock,” Reddoch-Cardenas said.

And, an ongoing trial in Norway has found that “transfusion of seven-day refrigerated platelets in [platelet additive solution] to cardiac surgery patients caused no risk of adverse effects, better aggregation responses than room temperature platelets and effectively lowered postoperative bleeding,” she added.

A variety of tests conducted by the Army researchers demonstrated that refrigerated platelets perform better than platelets stored at room temperature. “In our studies, we have shown that room temperature samples stored for five days show a dramatic reduction in aggregation, lose the ability to adhere to collagen and form weak clots that are susceptible to lysis. In contrast, refrigerated samples stored for up to 21 days show equivalent, if not superior function, compared to five-day room temperature samples in all of the aforementioned tests,” Reddoch-Cardenas explained.

Refrigeration offers other, nonclinical advantages. Platelets could be stored with other blood products and, without the need for constant agitation, would no longer need bulky agitators. Refrigeration also would reduce the cost of testing for bacterial contamination, she noted.

The Army research has already led to the extension of cold platelet shelf life to 72 hours and enabled the DoD to obtain a variance to collect and transfuse 14-day cold stored platelet in military treatment facilities.

“The next step to stem from our research is to obtain a licensed 14-day cold-stored platelet product that can be used to treat actively bleeding patients in both the military and civilian sector,” according to Reddoch-Cardenas. Getting to that point will require participation and clinical data from hospitals across the country to ensure the safety and efficacy of the platelets, she said.

“We’re just beginning to scratch the surface of the potential that cold-stored platelets have at treating bleeding in patients suffering from trauma and hematological malignancies,” she noted, “but there’s always more work to be done.”

1. Ketter P, Cap AP. Platelet metabolism during room temperature storage contributes to bacterial growth: Effect mitigated by refrigeration. ASH 2018. Abstract 3822. December 3, 2018.

2. Murphy S, Gardner FH. Platelet Preservation: Effect of Storage temperature on maintenance of platelet viability—Deleterious effect of refrigerated storage. NEJM. May 15, 1969; 280:1094-1098.

3. Reddoch KM, Pidcoke HF, Montgomery RK, Fedyk CG, Aden JK, Ramasubramanian AK, Cap AP. Hemostatic function of apheresis platelets stored at 4oC and 22oC. Shock. 2014;41 Suppl1 (0 1):54-61.



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