Storage and transfusion of platelets : In vitro and in vivo studies in healthy volunteers and in allogeneic hemapoetic progenitor cell transplant recipents

Abstract: Early studies in the 1960´s showed that platelet (PLT) transfusions significantly reduced the incidence of fatal hemorrhages. Together with the advances in the hematology and transplantation field, easily accessible PLTs for transfusion use have resulted in a rapid increase of PLT utilization and a change from therapeutic-i.e., treatment of clinical bleeding- to prophylactic PLT transfusions, despite limited clinical evidence regarding whether a prophylactic PLT transfusion strategy results in a lower morbidity or mortality compared with transfusing patients with early signs of bleeding. About 2 million PLTs are transfused in the United States, 2.9 million in Europe and 40 000 in Sweden with a roughly tenfold increase since 1984. In a 1991 survey in the United States, more than 70% of hospitals reported transfusing PLTs primarily for prophylaxis. Continued increase in demand may result in problems with shortages and difficulties to comply with orders. Several in vitro studies have shown satisfactory quality results for platelets stored for 7 days and even longer. Storage has been limited to 5 days because of the risk of bacterial contamination, with subsequent bacterial increase during storage at room temperature. Provided that contaminating bacteria can be effectively detected or put out of action in platelets, prolonged storage represents one possibility to obtain improved availability, logistical management and decreased outdating. The overall aim of this thesis was to assess the quality of platelets after prolonged storage up to 7 days and to evaluate the consequences of lowering the platelet transfusion trigger for prophylactic transfusion, representing two possible approaches suggested to have impact on the platelet accessibility. In paper I, we showed that a prophylactic platelet transfusion trigger level of 10 instead of 30 x109 platelets/L for allogeneic HPCT recipients considerably reduced the number of PLT transfusions without increasing the incidence of hemorrhagic events. In paper II, recovery and survival in healthy volunteers of PLTs stored for 7 days decreased, but met the suggested criteria. Analyzed in vitro parameters showed acceptable results. Addition of potassium and magnesium to the storage medium indicated higher quality in vitro but this could not be verified by in vivo recovery and survival (paper III). In paper IV, when comparing transfusion in allogeneic HPCT recipients of PLTs stored for 6-7 days vs 1-5 days, a significant lower platelet increment (CCI) and shorter interval between transfusions was noticed with prolonged storage. To have sufficient PLTs of excellent quality in stock at any given time to provide to patients in great need represents a difficult challenge to transfusion services. If prolonged storage results in decreased time between the transfusion and more PLTs are transfused in general the result might not be what was aimed at. In that case it might be wiser to question the need of prophylactic transfusion. Lately it has been proposed that patient selection may be the key to the safety of therapeutic only based platelet transfusion strategy. To conclude, there is a growing need of further randomized, controlled clinical trials to establish the therapeutic approaches that maximizes the quality of patient care in different patient categories while minimizing expenses to transfusion services and the health care system to be able to ensure an adequate PLT supply when really needed.