Current opinion in hematology
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Curr. Opin. Hematol. · Sep 2003
ReviewThe association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome occurs more commonly in women and among women is commonly associated with pregnancy. Case series of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome from 1964 to 2002 were reviewed (1) to document the reports of occurrence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy and (2) to search for reports of women with congenital or familial thrombotic thrombocytopenic purpura-hemolytic uremic syndrome who were initially diagnosed during their first pregnancy. ⋯ These other syndromes may also be associated with thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal insufficiency, making their distinction from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome difficult or impossible. The occurrence of preeclampsia and related syndromes, the hypercoaguable state that occurs in late pregnancy and postpartum, and the progressively decreasing concentration of ADAMTS13 that occurs during late pregnancy may combine to increase the risk for occurrence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
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Thrombotic thrombocytopenic purpura (TTP) has been a mysterious and deadly disease that often could be treated effectively by plasma exchange, but without real understanding of the underlying pathophysiology. Recent advances now suggest that deficiency of a specific von Willebrand factor (VWF) cleaving protease promotes tissue injury in TTP. VWF multimers participate in the formation of platelet thrombi. ⋯ The VWF cleaving protease proves to be a new member of the ADAMTS family of metalloproteases, designated ADAMTS13. Autoantibodies that inhibit ADAMTS13 cause sporadic TTP, and mutations in the ADAMTS13 gene cause an autosomal recessive form of chronic relapsing TTP. Further studies of ADAMTS13 seem likely to change our approach to the diagnosis and treatment of TTP and other thrombotic microangiopathies.
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The ability to use an effective treatment constitutes a main concern in the management of acute ischemic stroke. Randomized trials have so far failed to demonstrate any beneficial effect of neuroprotective agents on neurologic outcome after an acute stroke. ⋯ Among them, a single randomized trial, the National Institute of Neurological Diseases and Stroke Trial, showed a beneficial effect of thrombolysis on outcome after an acute ischemic stroke with a significant increase in the number of patients with no or minimal disability at 3 months in the group receiving intravenous recombinant tissue plasminogen activator (rt-PA) compared with placebo. However, there was no reduction in mortality and there was, as in all other trials, a significant increase in the risk of symptomatic intracerebral hemorrhage (ICH).
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Curr. Opin. Hematol. · Jul 2002
ReviewMolecular mechanisms of resistance to STI571 in chronic myeloid leukemia.
Therapeutic use of the recently FDA-approved drug STI571 has been successful in the treatment of Philadelphia chromosome-positive leukemias. STI571 is a small molecule inhibitor with activity against BCR-ABL, the deregulated tyrosine kinase responsible for initiation and maintenance of the disease in the chronic phase of chronic myeloid leukemia (CML). ⋯ Studies investigating the molecular mechanisms of resistance to this novel compound have progressed rapidly and point to the continued importance of BCR-ABL in disease maintenance even at its latest stages. Here the authors review recent work aimed at elucidating the nature of STI51 resistance.
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It has long been believed that mammalian stem cells are irreversibly committed to the individual tissue in which they reside; however, several recent studies have challenged this assertion and suggest a remarkable plasticity of stem cells derived from various adult tissues. Hematopoietic stem cells have been central to this paradigm shift, and in this review, the authors discuss the recent advances in this rapidly growing field. Although several exciting findings in rodents have already led to clinical trials in humans, true stem cell plasticity has not rigorously been established in most, if not all, studies to date, and a number of issues remain unresolved. Large animal models should prove invaluable to the progress of the field.