Quality is important within the blood banking and cellular therapy communities, and platelets are no exception. Ensuring that stored platelets will survive in circulation and perform their hemostatic functions helps save approximately 35,000 lives annually. However, because approximately 1 in every 6 transfusions is not effective (due either to alloimmunization, patient condition or problems with the unit), patients do not always get the hemostatic support they need, and additional units of platelets are needed to help them.
Determining whether platelet units are as viable and functional as they could be presents certain challenges. There are three types of tests for measuring platelet quality as a new collection or storage system being considered for licensure — in vitro biochemical, hematologic and functional tests; in vivo radiolabelled autologous recovery and survival tests; and patient clinical trials — which can provide some insight into platelet quality. However, none of these approaches provides a simple and reliable means of assessing the quality of a unit right before transfusion.
Elisabeth Maurer-Spurej, PhD, a scientist at Canadian Blood Services in Vancouver, discussed the use of in vitro studies, which are the most fundamental of the three tests. There are several types of these tests — swirling, morphology score, response to agonists (“extent of shape change”), metabolic function in response to hypotonic shock, expression of extracellular markers, microparticle formation and platelet count — but none consistently predicts patient care outcomes.
“There is no routine, reliable quality commercial test that is easy to do,” Maurer-Spurej said. The company she founded, LightIntegra Technology Inc., is hoping to change that. LightIntegra is in the process of developing ThromboLUX, a new platelet test that may be able to better predict transfusion outcomes.
In vivo tests, which are more clinical in nature than in vitro tests, can determine platelets’ recovery and survival. They provide a more “real-life” scenario by documenting what happens to platelets when they are transfused and tracking them with radioactive tagging, according to James AuBuchon, MD, president and CEO of Puget Sound Blood Center. Unlike red cell storage systems, platelets have no absolute criterion of acceptability, and simply comparing a new system with a previous one sets up the potential for a slippery slope of creeping inferiority.
According to AuBuchon, the late platelet guru Scott Murphy, MD, proposed comparing the new system’s platelets at the end of storage with fresh platelets from the same research subject. As adopted by the Food and Drug Administration, these platelets should show 67 percent of the recovery and 58 percent of the survival of fresh platelets, standards that current systems meet and that provide adequate platelet longevity for patients. Investigators also are developing and validating mouse models to assess the storage of human platelets.
The results of clinical trials that examined the efficacy of different types of platelets were presented by Alan Tinmouth, MD, MSc, a clinical epidemiologist at Ottawa Hospital Research Institute. According to Tinmouth, data indicates platelet transfusions are effective in reducing bleeding in thrombocytopenic patients, but how to quantify the effect of platelet transfusions has been difficult to answer.
The amount of patient bleeding can measure platelet efficacy, Tinmouth said. Unfortunately, surrogate measures, such as stool bleeding loss and bleeding time, do not provide as robust data, so larger studies are necessary. The World Health Organization scale for bleeding has been most commonly used in clinical trials, but there remains variability in the reporting and analysis of bleeding events, which can present difficulties in interpreting the results of clinical trials evaluating platelet efficacy.
One recent study investigated clinical efficacy of platelets stored in platelet additive solutions compared with plasma and found no difference in bleeding between the two groups. Adverse transfusion reactions occurred less often with the additive solution approach. Other recently published studies have assessed the clinical efficacy and safety of platelets prepared with a pathogen inactivation technology compared with untreated components by assessing bleeding. The results, Tinmouth said, show that “pathogen-inactivated platelets appear to be as clinically effective” in preventing bleeding, although additional studies still may be needed.
Tinmouth concluded his remarks by emphasizing the importance of platelets in transfusion medicine and said that, in the future, platelets that offer enhancements (e.g., pathogen inactivation) or platelet alternatives should undergo robust evaluation of clinical bleeding using a validated tool to ensure adequate function.
All of these approaches are used in combination to assess new platelet systems with the goal of identifying improvements in platelet viability and function.
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