British journal of haematology
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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.