Journal of thrombosis and haemostasis : JTH
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J. Thromb. Haemost. · Aug 2006
ReviewManagement of patients with refractory immune thrombocytopenic purpura.
In immune thrombocytopenic purpura (ITP), thrombocytopenia is a result of both increased platelet destruction and insufficient platelet production. In adults, the course is commonly chronic, but most patients never experience serious bleeding even with severe thrombocytopenia. In case series of consecutive adult patients identified at the time of diagnosis, the frequency of death from bleeding is low, < 1%. ⋯ Immunosuppressive agents, including rituximab and combinations of agents, may be less effective than splenectomy in achieving complete remissions and the remissions may also be less durable. New agents for patients with ITP are currently in development that enhance platelet production, rather than diminish platelet destruction. In preliminary reports, these agents have been effective in maintaining safe platelet counts in patients with chronic ITP that was refractory to splenectomy and other treatments.
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J. Thromb. Haemost. · Jun 2006
ReviewPharmacoeconomics of anticoagulation therapy for stroke prevention in atrial fibrillation: a review.
Atrial fibrillation (AF) increases the risk of ischemic stroke 5-fold and may not only be responsible for as many as 15% of all strokes that occur but also for larger and more disabling strokes than those attributable to other causes which increase the associated costs of care. Anticoagulation with warfarin in the target INR of 2.5 is a major clinical challenge in real-life practice, given that the complex relationship between warfarin dosage and response is readily altered by a variety of factors such as concurrent medications, illnesses, genetic influences, and dietary/lifestyle changes. Consequently, INR values are out of the target range approximately half of the time in real-life studies compared to clinical trial setting. Current anticoagulation therapies are less likely to be cost-effective in routine clinical practice and need improvement. The aim of this review is to discuss the pharmacoeconomic consequences of this management strategy by analysing the optimal treatment option within specific age and risk groups, confirming current guidelines for a health economic perspective and considering the economic impact on health care policy. ⋯ Improvement could be achieved by optimising physicians and patient's knowledge driven through prevention campaigns by health care policy.
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J. Thromb. Haemost. · Aug 2005
ReviewSignificance of the transcription factor KLF5 in cardiovascular remodeling.
Structural remodeling of the heart and blood vessels is an important pathologic process in the development of many cardiovascular diseases. However, transcriptional regulation of altered gene expression during cardiovascular remodeling is not well understood. We previously isolated KLF5/basic transcription element-binding (BTEB)2, a Krüppel-like factor, as a transcription factor that binds the promoter of the embryonic smooth muscle myosin heavy chain gene (SMemb). ⋯ KLF5 activities are regulated by many transcriptional regulators and nuclear receptors, such as retinoic acid receptor-alpha (RAR alpha), NF-kappaB, PPAR gamma, p300, and SET. Interestingly, RAR alpha agonist suppresses KLF5 and cardiovascular remodeling, whereas RAR alpha antagonist activates KLF5 and induces angiogenesis. These results indicate that KLF5 is an essential transcription factor in cardiovascular remodeling and a potential therapeutic target for cardiovascular disease.
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This overview summarizes the history of thrombotic thrombocytopenic purpura (TTP) from its initial recognition in 1924 as a most often fatal disease to the discovery in 1997 of ADAMTS-13 deficiency as a major risk factor for acute disease manifestation. The cloning of the metalloprotease, ADAMTS-13, an essential regulator of the extremely adhesive unusually large von Willebrand factor (VWF) multimers secreted by endothelial cells, as well as ADAMTS-13 structure and function are reviewed. The complex, initially devised assays for ADAMTS-13 activity and the possible limitations of static in vitro assays are described. ⋯ We believe that, at present, patients without severe acquired ADAMTS-13 deficiency should be treated with plasma exchange as well, until better strategies become available. Constitutional TTP can be treated by simple FFP infusion that rapidly reverses acute disease and--given prophylactically every 2-3 weeks--prevents relapses. There remains a large research agenda to improve diagnosis of TMA, gain further insight into the pathophysiology of the various TMA and to improve and possibly tailor the management of affected patients.