ABSTRACT
Immunization against the platelet αIIbß3 glycoprotein due to blood transfusion represents one of the most severe complications in Glanzmann thrombasthenia (GT) disease. Anti-αIIbß3 isoantibodies development may lead to ineffective platelet transfusion and can, in case of pregnancy, cross the placenta leading to fetal thrombocytopenia. We describe here the case of a girl with type I GT who developed high rates of anti-αIIbß3 isoantibodies after first and unique blood transfusion. Surprisingly, this patient had only received red blood cell concentrates and immunization was presumably stimulated by the residual presence of platelets in concentrates. This study emphasizes the need for regular anti-αIIbß3 antibodies screening in GT, even though patients have never been previously transfused with platelet concentrates.
Subject(s)
Thrombasthenia , Pregnancy , Female , Humans , Thrombasthenia/diagnosis , Isoantibodies , Platelet Glycoprotein GPIIb-IIIa Complex , Blood Platelets , Platelet Membrane Glycoproteins , ErythrocytesABSTRACT
We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery.
ABSTRACT
The goal of this study was to assess the interaction of the mTOR inhibitors (ImTORs) sirolimus and everolimus with the human organic anion-transporting polypeptides (OATPs) expressed in hepatocytes and enterocytes by conducting uptake experiments using (i) transfected HEK293T cells, (ii) the hepatocyte-like HepaRG cell line and (iii) the enterocyte-like Caco-2 cell line. Sirolimus and everolimus inhibited in a dose-dependent manner the uptake of [³H]-estrone sulphate by OATP1A2 and OATP1B1 and that of mycophenolic acid 7-O-glucuronide (MPAG) by OATP1B3. ImTOR apparent 50% inhibitory concentrations (IC50) for OATPs were 11.9 µM (OATP1A2), 9.8 µM (OATP1B1) and 1.3 µM (OATP1B3) for sirolimus and 4.2 µM (OATP1A2), 4.1 µM (OATP1B1) and 4.3 µM (OATP1B3) for everolimus. No transport of sirolimus or everolimus by OATP1A2, OATP1B1 or OATP1B3 was observed in HEK-transfected cells and the OAT/OATP/MRP chemical inhibitor probenecid did not significantly decrease the uptake of sirolimus and everolimus in HepaRG and Caco-2 cells, but tended to increase their intracellular accumulation presumably through efflux inhibition. In conclusion, our data suggest that the major OATP transporters expressed in the liver and the intestine do not contribute to the pharmacokinetics of sirolimus and everolimus. However, ImTORs are inhibitors of these transporters.
