This article reviews evidence for the involvement of cell-derived microparticles (MP) in transfusion-related adverse events. The controversy concerning possible added risk of older vs. fresher stored blood is also reviewed, and is consistent with the hypothesis that MP are involved with adverse events. Although all types of circulating MP are discussed, the emphasis is on red cell-derived MP (RMP). The evidence is particularly strong for involvement of RMP in transfusion-related acute lung injury (TRALI), but also for post-operative thrombosis. However, this evidence is largely circumstantial. Work in progress to directly test the hypothesis is also briefly reviewed.
Recurrence of focal glomerulosclerosis (FSGS) following renal transplantation is a common cause of allograft loss and clinical morbidity. Recent attempts to control proteinuria and morbidity with plasmapheresis (PP) have met with limited success. Our experience with the use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the management of refractory FSGS pre transplant suggested its potential benefit in post-transplant recurrence. This report presents our 25-year experience in pediatric renal transplantation of patients with FSGS divided into two treatment eras: Era 1-prior to use of daclizumab (anti-IL-2R) and Era 2-after daclizumab. A total of 179 pediatric patients were transplanted during the 25-year period. FSGS was confirmed in 27 (15%); 16 of 28 allografts (57%) had recurrence of FSGS during the post-transplant period. In Era 1, only 6 of 16 (38%) recurred in the allograft, while 10 of 12 (83%) recurred during Era 2. The odds ratio of recurrence of FSGS in the allograft after induction with anti-IL-2R was 8.3 (95% confidence interval=1.3-52, P =0.02). Only 2 patients in Era 1 received PP, while 10 in Era 2 were entered into an intensive PP protocol followed by maintenance with AB consisting of angiotensin receptor blockers alone, or in combination with angiotensin-converting enzyme inhibitor. Although proteinuria decreased an average of 80+/-16% with PP, the response was variable and severe morbid edema persisted in poor responders. Maximum benefit occurred with the addition of AB and MMF. After a follow-up of 27+/-15 months, proteinuria has shown a sustained decrease of 94+/-8% below baseline. In conclusion, our experience suggests that, with recurrent FSGS, a limited course of PP followed by maintenance therapy with AB and MMF improves symptoms and may preserve allograft function.
The serum cytokine profile in thrombotic thrombocytopenic purpura (TTP) has not been extensively characterized. In this pilot study, a novel technique was utilized to evaluate multiple cytokines in patients with idiopathic TTP during a course of plasma exchange (PE). Single serum samples were obtained from five TTP patients before and after each PE. Random sera were obtained from nine healthy volunteers who served as controls. The samples were evaluated for 13 cytokines (IL-1B, IL-2 , IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IFN-g , GM-CSF, and TNF-a) using the Luminex bead array (LINCOplex) multianalyte detection system that permits simultaneous detection of multiple cytokines from a single sample. Each patient received 4-6 PEs (Cobe Spectra) with 3.0-4.0 L of fresh frozen plasma as replacement fluid. Four of 5 patients received corticosteroids prior to and during PE. The control group did not receive steroids. Baseline values for IL-8 (182.9 vs. 6.5 pg/mL, P < 0.05) and TNF-a (11.4 vs. 0.9 pg/mL, P < 0.001) were significantly higher in TTP patients compared with controls. Other tested cytokines were not significantly different between the two groups. Comparison of cytokine values pre-and post-PE indicate a substantial decrease after each PE. However, cytokines rebounded to abnormal levels by the following day. There was no correlation between cytokines and serum LDH or platelet count. These findings suggest that certain cytokines, particularly IL-8 and TNF-a, are altered in TTP, and this may indicate a direct role in TTP pathogenesis, reflect ongoing tissue injury, or perhaps indicate an inadequate attempt to limit tissue injury.
RBC alloimmunization can present a special challenge to solid-organ transplantation. Early serologic testing of the recipient pretransplant and prompt communication between the transfusion service and transplant team facilitates successful transfusion management of these patients.
Stiff‐man syndrome (STS) is a rare neurological disorder characterized by involuntary axial and proximal limb rigidity and continuous motor unit activity on electromyography (EMG). Autoantibodies to glutamic acid decarboxylase (GAD) present in 60% of the patients are implicated. We report on the use of plasma exchange (PE) in 2 patients with STS whose serum and cerebrospinal fluid were negative for GAD autoantibodies. One patient showed minimal clinical improvement following PE while the second reported subjective improvement, but not any different from that with medications. Based on the results of PE in our patients, it seems that those who are autoantibody negative are less likely to respond. Whether a more aggressive approach to PE will be beneficial remains speculative.
Coulter volume is far more accurate measure of cell volume than forward angle light scatter. In this report, we have used Coulter volume to determine the mean cell volume and diameter of normal human peripheral blood cells and hematopoietic progenitor cells obtained by apheresis (HPC-A) from patients with hematological malignancies. Fresh peripheral blood samples (treated with Beckman Coulter IMMUNOPrep erythrocyte lysis solution), HPC-A samples (treated with BD Biosciences FACSLysing solution), or processed by Ficoll Hypaque sedimentation method were stained with CD45-FITC and PE-labeled CD34, CD90, CD117, and CD133 antibodies and analyzed for electronic volume and two color fluorescence. The mean electronic volume and diameter of mononuclear cells from fresh peripheral blood samples prepared with IMMUNOPrep were lymphocytes (191 lm 3 , 7.16 lm), monocytes (370 lm 3 , 9.91 lm), and granulocytes (328 lm 3 , 8.56 lm). In mononuclear cells of HPC-A samples prepared by Histopaque-1077 sedimentation, the lymphocytes had volume and diameter of 311 lm 3 , 8.4 lm, monocytes were 486 lm 3 , 9.76 lm, and granulocytes were 515 lm 3 , 9.95 lm.
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