To determine the relative importance of clinical factors on the efficacy of platelet transfusions, 941 pooled platelet transfusions from HLA-unmatched donors were studied prospectively in 133 patients with bone marrow failure. Multiple linear regression analyses identified the major factors influencing one-hour-corrected increments (CI) as prior splenectomy, bone marrow transplantation, disseminated intravascular coagulation, concurrent intravenous amphotericin B, splenomegaly, and HLA antibody grade. The relative impact of these factors on CI has been quantitated by using a formula developed from these data. A linear relationship was demonstrated between increasing percentage of HLA antibody grade and decreasing CI. A number of other factors were less important in the linear regression model than the aforementioned major factors. These included platelet-specific antibodies, concurrent antibacterial antibiotics, clinical bleeding grade, and temperature. Factors that did not influence CI included the number of prior platelet transfusions, prior granulocyte transfusions, prior red cell transfusions, infection, age, blood group, diagnosis, sex, pretransfusion platelet count, prior pregnancies, and concurrent antineoplastic drugs. This study identified major clinical factors that significantly influenced CI and were major causes of refractoriness to pooled platelet transfusions.
Glycolysis and oxidative metabolism were assessed in washed human platelets incubated in a Ca++ and Mg++ free Krebs-Ringer bicarbonate buffer, pH 7.4 at 37° C for 1 hour. Glycolytic rate was 45-65 per cent lower under aerobic than anaerobic conditions. Glycolysis was decreased further when albumin was present in the incubation medium and under these conditions glucose uptake, glycogen utilization and lactate production were 21.4, 15.8 and 78 µmoles/hr. per 1011 platelets, respectively. The oxidation of 6-14C glucose was 0.39 µmoles/hr. per 1011 platelets and of U-14C palmitate 0.19 µmoles/hr. per 1011 platelets, and the rate of oxidation of either substrate was increased in the absence of the other. The uncoupling agent, dinitrophenol, stimulated oxidation of glucose to a much larger extent than fatty acid. It is concluded that both glycolysis and oxidative phosphorylation are important to platelet energy metabolism, that either pathway may compensate for decreased activity of the other and that, under conditions of metabolic stress, glucose is preferred to fatty acids as a substrate for oxidative metabolism.
Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens. HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies. The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months. In two patients this occurred whilst still receiving platelet transfusions. Antibody reappeared in only two of six patients subsequently transfused. Antibodies to platelet specific antigens were detected in 28 patients. They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity. There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens. Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies. These findings have important implications for the selection of platelet donors for alloimmunized recipients.
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