British journal of haematology
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Depletion of B lymphocytes using the anti-CD20 monoclonal antibody rituximab has wide-spread use in the treatment of patients with autoimmune disorders. As haematopoietic progenitor cells and only a fraction of differentiated plasma express CD20, the effect of rituximab on immune function appears to be minimal. ⋯ Reactivation of latent JC virus, resulting in progressive multifocal leucoencephalopathy, and hepatitis B virus, resulting in hepatoxicity, have been documented in patients receiving rituximab; although confounding effects of concomitant immunosuppressive therapies and immune dysregulation due to the underlying disease make causal associations of infections problematic. This review discusses the efficacy of B cell depletion therapy in the treatment of autoimmune diseases, the effect of B cell depletion on infection and immunity including the role of the B cell in autoimmunity, and identifies areas of controversy.
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Progressive degeneration of the central nervous system leading to the loss of neuromotor, neurophysiological and cognitive abilities is the fundamental clinical problem in patients with many inherited metabolic diseases (IMD). Worldwide experience shows that morbidity, quality of life, and survival in these patients can be improved by allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed early in the course of the disease. At present, while available for some conditions, exogenous enzyme replacement therapy is unable to correct cognitive and central nervous system disease because of its inability to cross the blood-brain barrier. ⋯ Traditionally, bone marrow has been the graft source for IMD patients. However, in the last 5 years many studies utilizing unrelated donor umbilical cord blood (UCB) as a graft source have demonstrated that UCB provides rapid and increased access to transplantation with favourable outcomes. This review describes preclinical studies and past and present clinical treatment approaches and discusses current controversies and future directions of this promising field.
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Liver disease impacts on both primary and secondary haemostatic mechanisms and historically these changes were thought to underpin the bleeding diathesis. However, bleeding complications in patients with liver disease are unpredictable, with the majority of haemorrhagic episodes occurring as a result of porto-systemic varices. ⋯ Routine laboratory tests do not reliably predict the risk of haemorrhage and the optimal management strategy to avert potential bleeding complications is yet to be established. There may be a future role for global coagulation assays, such as thrombelastography and thrombin generation, in both stratifying the risk of bleeding and guiding management of these patients.
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Neuraxial anaesthesia is increasingly performed in thrombocytopenic patients at the time of delivery of pregnancy. There is a lack of data regarding the optimum platelet count at which spinal procedures can be safely performed. ⋯ It is likely that lower platelet counts may also be safe but there is insufficient published evidence to make recommendations for lower levels at this stage. For patients with platelet counts of 50-80 x 10(9)/l requiring epidural or spinal anaesthesia and patients with a platelet count 20-40 x 10(9)/l requiring a lumbar puncture, an individual decision based on assessment of risks and benefits should be made.
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Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality world-wide. Although first described in 1983, it took two decades to develop consensus definitions, which remain controversial. The pathogenesis of TRALI is related to the infusion of donor antibodies that recognize leucocyte antigens in the transfused host or the infusion of lipids and other biological response modifiers that accumulate during the storage or processing of blood components. ⋯ This review demonstrates that critically ill patients are more susceptible to TRALI and require special attention by critical care specialists, haematologists and transfusion medicine experts. Further research is required into TRALI and its pathogenesis so that transfusions are safer and administered appropriately. Avoidance including male-only transfusion practises, the use of leucoreduced components, fresher blood/blood components and solvent detergent plasma are also discussed.