The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC). A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.
Blood is usually irradiated by x-ray to prevent graft-versus-host-disease. However, plasma potassium levels of irradiated blood are rapidly increased during preservation in irradiated blood. The objectives of this study were to develop a rapid blood transfusion system for which irradiated blood can be used and to evaluate the capability of blood purification of the system. Packed red blood cells (RBC) were irradiated (15 Gy x-ray) at 21 days and preserved until 42 days after collection. A blood mixture of RBC and plasma was perfused through a dialyzer at 25, 50, 100, and 200 ml/min. Dialysate was perfused at 100, 100, 500, and 500 ml/min, respectively. Preperfusion levels of sodium, 121; potassium, 35; and chlorine, 76 mEq/L were changed to sodium, 144 to 146; potassium 2.5 to 3.0; and chlorine, 105 to 110 mEq/L, which were comparable with the levels in dialysate after perfusion for 25, 50, and 100 ml/min perfusion groups. For the 200 ml/min perfusion group, potassium was 5.3 mEq/L after perfusion which was slightly higher than other groups, but 84% of the potassium was removed by the system. Citrate levels were significantly decreased to 3.4, 28, 31, and 81 mg/dl for the 25, 50, 100, and 200 ml/min groups, respectively, after perfusions. The rapid transfusion system composed of the dialyzer and the blood pumps was effective in the removal of potassium and in the normalization of electrolytes. Irradiated blood with high levels of potassium can be safely and effectively used for this system in cases requiring massive rapid blood transfusion.
We observed the presence of a new autoantibody, anti-erythrocyte protein 4.1, in a patient with autoimmune hemolytic anemia (AIHA). Western blotting analysis revealed that IgG from the patient's plasma reacted with erythrocyte protein 4.1. However, among other patients with hemolytic diseases (six having AIHA and three each having either hereditary spherocytosis, elliptocytosis, or lead poisoning) as well as among control subjects, no antibody activity to protein 4.1 was observed. In addition to the anti-protein 4.1 antibody, two different kinds of anti-erythrocyte antibodies were detected by conventional serological studies in this patient. One of them was an anti-Ena-like antibody in the eluate from the patient's erythrocytes, while another was the anti-S-specific antibody in the plasma. An elution study and an absorption study using S antigen-positive erythrocytes demonstrated that the anti-protein 4.1 antibody differed from both the anti-Ena-like antibody and the anti-S antibody. Familial analysis of the patient revealed the same antibody in her brother, who did not have hemolytic anemia. These results demonstrate that anti-protein 4.1 antibody is considered to be included in the spectrum of anti-cytoskeleton autoantibodies, which have been observed in patients having increased cell lysis as well as in healthy subjects.
Platelet product derived from single donor plateletpheresis is required to reduce the risks of adverse reactions by blood transfusion. The objectives of this study are to evaluate the status of platelet collection and its efficacy by various kinds of plateletpheresis equipment and to assess the achievement of platelet transfusion by platelet product derived from a single donor. Since the blood centers have introduced some kinds of efficient plateletpheresis equipment, large units of platelet products have been supplied mainly for the patients. Amicus and CCS might be preferable plateletpheresis machines because of their collection efficiencies and wider indication for donors. The average number of donors of platelet product per patient has recently reached nearly 1.0, and around 90% of patients have received platelet product derived from a single donor in the recent several years. However, platelet transfusion derived from a single donor has not yet been completely achieved. Each regional blood center should seriously consider the efficacy of each plateletpheresis equipment and arrange the equipment to collect platelets more effectively to achieve platelet transfusion from a single donor.
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