British journal of haematology
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Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their formation and/or persistence. We therefore developed CPHPC ((R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl]pyrrolidine-2 carboxylic acid), a novel bis(D-proline) drug, to specifically target SAP and report here a first, exploratory, open label proof of principle study in systemic amyloidosis. CPHPC produced sustained, >95% depletion of circulating SAP in all patients and c. 90% reduction in the SAP content of the two amyloidotic organs that became available. ⋯ No accumulation of amyloid was demonstrable by SAP scintigraphy in any patient on the drug. In hereditary fibrinogen amyloidosis, which is inexorably progressive, proteinuria was reduced in four of five patients receiving CPHPC and renal survival was prolonged compared to a historical control group. These promising clinical observations merit further study.
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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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Case Reports
Extracorporeal membrane oxygenation as a rescue therapy for leukaemic children with pulmonary failure.
In patients with leukaemia, acute respiratory distress syndrome (ARDS) secondary to intensified chemotherapy-induced immunosuppression is a devastating disorder resulting in high morbidity and mortality. Compared to standard indications for extracorporeal membrane oxygenation (ECMO), cytopenia further increases the risks of infection and bleeding. We describe the use of ECMO in four children with ARDS and leukaemia. ⋯ All patients had a highly increased demand for packed platelet and red blood cell transfusions. This increased demand and unmanageable chronic bleeding into both lungs in one patient were probably caused by a combination of coagulopathy from the primary illness, the use of anticoagulants, chemotherapy-induced cytopenia, and a reduced survival rate of platelets and red cells due to permanent contact to foreign surface. We concluded that ECMO is a supportive tool to reduce the incidence of early death, treatment-related mortality and, ultimately, to improve overall survival in childhood leukaemia.