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1.
Erkan D Derksen R Levy R Machin S Ortel T Pierangeli S Roubey R Lockshin M 《Lupus》2011,20(2):219-224
The Antiphospholipid Syndrome (APS) Clinical Research Task Force (CRTF) was one of six Task Forces developed by the 13(th) International Congress on Antiphospholipid Antibodies (aPL) organization committee with the purpose of: a) evaluating the limitations of APS clinical research and developing guidelines for researchers to help improve the quality of APS research; and b) prioritizing the ideas for a well-designed multicenter clinical trial and discussing the pragmatics of getting such a trial done. Following a systematic working algorithm, the Task Force identified five major issues that impede APS clinical research and the ability to develop evidence-based recommendations for the management of aPL-positive patients: (1) aPL detection has been based on partially or non-standardized tests, and clinical (and basic) APS research studies have included patients with heterogeneous aPL profiles with different clinical event risks; (2) clinical (and basic) APS research studies have included a heterogeneous group of patients with different aPL-related manifestations (some controversial); (3) thrombosis and/or pregnancy risk stratification and quantification are rarely incorporated in APS clinical research; (4) most APS clinical studies include patients with single positive aPL results and/or low-titer aPL ELISA results; furthermore, study designs are mostly retrospective and not population based, with limited number of prospective and/or controlled population studies; and (5) lack of the understanding the particular mechanisms of aPL-mediated clinical events limits the optimal clinical study design. The Task Force recommended that there is an urgent need for a truly international collaborative approach to design and conduct well-designed prospective large-scale multi-center clinical trials of patients with persistent and clinically significant aPL profiles. An international collaborative meeting to formulate a good research question using 'FINER' (Feasible; Interesting; Novel; Ethical; and Relevant) criteria took place in November 2010. 相似文献
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Structural model of human ceruloplasmin based on internal triplication, hydrophilic/hydrophobic character, and secondary structure of domains. 总被引:9,自引:4,他引:9 下载免费PDF全文
T L Ortel N Takahashi F W Putnam 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(15):4761-4765
A molecular model for the structure of human ceruloplasmin is proposed that is based on the determination of the complete amino acid sequence, studies of the products of limited proteolytic cleavage, calculations of the hydrophilic/hydrophobic character (hydropathy profile), and predictions of the local secondary structure. This multicopper oxidase (Mr approximately 132,000) consists of a single polypeptide chain (1046 amino acid residues) with four attached glucosamine oligosaccharides. Computer-assisted statistical analysis of the internal repetition in the amino acid sequence confirms that the entire polypeptide chain is divided into three contiguous homology units, each containing about 350 amino acid residues. Each homology unit is subdivided into three domains, designated A1, A2, and B, that differ in structure and probably in function. Calculations of the hydropathy profile and predictions of the secondary structure support a molecular model based on internal repetition of three homology units and help to identify characteristic features of the interdomain junctions. The alignment scores for internal duplication of pairings of the three homology units of ceruloplasmin exceed the scores yet reported for contiguous internal duplication of any other protein. This highly significant evidence for intragenic repetition suggests that the ceruloplasmin molecule evolved by tandem triplication of ancestral genes coding for a primordial copper oxidase. 相似文献
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Charles L Bennett Benjamin Kim Anaadriana Zakarija Nicholas Bandarenko Dilip K Pandey Charlie G Buffie June M McKoy Amul D Tevar John F Cursio Paul R Yarnold Hau C Kwaan Davide De Masi Ravindra Sarode Thomas J Raife Joseph E Kiss Dennis W Raisch Charles Davidson J Evan Sadler Thomas L Ortel X Long Zheng Seiji Kato Masanori Matsumoto Masahito Uemura Yoshihiro Fujimura 《Journal of the American College of Cardiology》2007,50(12):1138-1143
OBJECTIVES: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). BACKGROUND: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). METHODS: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. RESULTS: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. CONCLUSIONS: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. 相似文献
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Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia often accompanied by microvascular ischemia, which may manifest as sensorimotor signs, visual changes, renal impairment, cardiac ischemia, and abdominal pain, depending on the organs affected. Until a few decades ago, TTP remained an almost universally fatal disorder. The introduction of plasma exchange therapy (PE) with replacement of fresh frozen plasma has improved the survival of patients with acute TTP dramatically from less than 10% to approximately 80 to 90% and is now considered the therapy of choice. During the last decade, the understanding of the pathophysiology of thrombotic microangiopathies, especially TTP, has increased considerably. The clinical features of thrombotic sequelae in TTP are diverse and usually secondary to microvascular thrombosis. Clinical and laboratory evidence for disruption of primary and secondary hemostasis, the role of endothelial integrity and fibrinolysis, the relevance of large vessel thrombosis, and the prevalence of thrombophilic states in TTP are discussed in this review. In summary, although the syndrome of TTP can sometimes be confused with other thrombotic diatheses, it is clear that the phenomenon of thrombosis in TTP appears to be distinctly different, both biologically and clinically, from other causes of microangiopathy and/or antibody-mediated thrombosis. Traditional anticoagulant and antiplatelet strategies are generally not effective in patients with TTP, despite the predominance of thrombotic manifestations, and common prothrombotic polymorphisms detected in patients with venous thromboembolism are seldom present. 相似文献
7.
Kitchens CS Erkan D Brandão LR Hahn S James AH Kulkarni R Pericak-Vance M Vance J Ortel TL 《The American journal of medicine》2011,124(4):290-296
Physicians periodically encounter patients with an extraordinarily accelerated course of hypercoagulability who develop thromboses in multiple organ systems over days to weeks. Such patients may harbor underlying hypercoagulable clinical conditions, but their clinical course sets them apart from most patients with similar risk factors. Underlying triggers of “thrombotic storm” include pregnancy, inflammation, trauma, surgery, and infection. Aggressive anticoagulant therapy may control thrombotic storm, yet thrombotic storm may resume with even brief interruptions of anticoagulant therapy. The authors of this communication formed the Thrombotic Storm Study Group in order to identify clinical characteristics of such patients, thus constructing preliminary criteria to better define, identify, and study the course of patients deemed to have thrombotic storm. The characteristics culled from these 10 patients are: younger age (oldest was 38 years old at time of presentation); at least 2 arterial or venous (or both) thromboembolic events, typically in unusual sites with or without microangiopathy; unexplained recurrence; and frequently proceeded by a trigger. The following characteristics were not used in defining thrombotic storm: underlying malignancies; use of acute myocardial infarction as a defining arterial event in the setting of established coronary artery disease; use of cocaine; thrombotic complications expected with various intravascular devices; known paroxysmal nocturnal hemoglobinuria or myeloproliferative disorders; severe trauma; and premorbid conditions. 相似文献
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Dowling NF Beckman MG Manco-Johnson M Hassell K Philipp CS Michaels LA Moll S Heit JA Penner J Kulkarni R Pipe S Bockenstedt P Andersen J Crudder S James AH Zimmerman S Ortel TL 《Journal of thrombosis and thrombolysis》2007,23(1):1-7
Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances
in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete
and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for
people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with
all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control
and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related
services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia.
The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention
services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies
to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development
of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators
and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient
outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools.
Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology,
surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the
centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From
August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits
to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers
and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients
receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate
future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation
disorders.
The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers
for Disease Control and Prevention. 相似文献
10.
Kaatz S Kouides PA Garcia DA Spyropolous AC Crowther M Douketis JD Chan AK James A Moll S Ortel TL Van Cott EM Ansell J 《American journal of hematology》2012,87(Z1):S141-S145
The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed. 相似文献