CURRENT CLINICAL INTERESTS
Evaluate whether pathogen reduction will allow extension of the storage time of platelets and whether it will also prevent alloimmunization to platelets when combined with filter-leukoreduction of platelets.
CURRENT RESEARCH INTERESTS
- Evaluate methods of extending platelet storage times;
- Assess viability and function of new platelet products; i.e., cryopreserved platelets, cold stored platelets, and lyophilized platelets;
- Initiate a large hematology/oncology patient transfusion trial of pathogen reduced platelets.
Evaluate Methods Of Extending Platelet Storage Times: Currently, platelets can be stored for only 5 days at room temperature (22°C). As it is not feasible to completely sterilize the venipuncture site, it is always possible that bacteria may enter the stored platelets resulting in an infectious risk to transfused thrombocytopenic patients. To extend storage beyond 5 days, it is very likely that the Food and Drug Administration (FDA) will require a pathogen reduction process. As pathogen reduction reduces platelet viability, we are conducting studies to determine how long pathogen reduced platelets can be stored and still meet FDA’s post-storage viability criteria.
Assess Viability And Function Of New Platelet Products:
- Cryopreserved Platelets: We have completed of a dose response safety study of cryopreserved platelets given to thrombocytopenic hematology/oncology patients. Our next study will be an efficacy study comparing bleeding outcomes in cardiac surgery patients.who are randomized to receive either standard platelets or cryopreserved platelets.
- Cold Stored Platelets: It is very difficult to supply platelet products to far-forward combat casualty care facilities. It has been known since the 1970’s that 22°C and 4°C stored platelets have almost the same post-transfusion platelet increments but platelet survivals are much better for 22°C stored platelets; i.e., approximately 5 days versus 1 day, respectively, in normal subjects given their autologous radiolabeled 3-day 4°C or 22°C stored platelets. To decrease transfusion frequency for hematology/oncology patients, blood centers routinely store platelets at 22°C. However, to maintain hemostasis long enough for wound repair, platelet survivals of only several hours may be needed. We are determining how long platelets can be stored at 4°C and maintain adequate post-storage viability and function.
- Lyophilized Platelets: Lyophilized platelets can be stored in small bottles on a shelf for periods of a year or more. We are currently doing a “first in human” dose response safety study of autologous lyophilized platelets given to normal subjects. If safety is demonsrated, follow-on studies will be radiolabeled autologous lyophilized platelet studies to determine recovery and survival kinetics and, finally, transfusion studies to determine hemostatic efficacy in patients who need platelet transfusions.
Initiate A Large Hematology/Oncology Transfusion Trial Of Pathogen Reduced Platelets in Patients: Currently, there is only one FDA licensed pathogen reduction process for platelets. However, there is another pathogen reduction process that is licensed in Europe but not in the U.S. I will be the principal investigator for a large multi-institutional 600 patient licensing trial to assess the safety and efficacy of the other pathogen reduction process. The primary endpoint will be days of bleeding in hematology/oncology patients randomized to standard or pathogen reduced platelets. The major secondary endpoint will be the rates of alloimmunization to platelets. In our dog platelet transfusion model, we have shown that leukoreduced/pathogen reduced platelets are 97% effective in preventing alloimmunization to donor platelets. This trial will allow us to determine whether leukoreduced/pathogen reduced platelets are similarly effective in patients.
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Slichter SJ, Bolgiano D, Corson J, Jones MK, Christoffel T. Extended storage of platelet-rich plasma prepared platelet concentrates in plasma or Plasmalyte. Transfusion 2010;50(10);2199-2209.
Dumont LJ, Dumont DF, Unger ZM, Siegel A, Szczepiorkowski ZM, Corson JS, Jones MK, Christoffel T, Pellham E, Bailey SL, Slichter SJ; for the BEST Collaborative. A randomized controlled trial comparing autologous radiolabeled in vivo platelet recoveries and survivals of 7-day stored platelet-rich plasma and buffy coat platelets from the same subjects. Transfusion 2011;51(6):1241-1248.
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Slichter SJ, Pellham E, Bailey SL, Christoffel T. Filtration leukoreduction followed by pathogen-reduction (Mirasol treatment) prevents alloimmune platelet refractoriness in a dog platelet transfusion model. Blood 2012;120(21):271.
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Slichter SJ, Corson J, Jones MK, Christoffel T, Pellham E, Bailey SL, Bolgiano D. Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS). Blood 2014;123(2):271-280.
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