Author
Indira Warrier
Bio: Indira Warrier is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Haemophilia B & Thrombocytopenic purpura. The author has an hindex of 12, co-authored 16 publications receiving 2194 citations.
Papers
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TL;DR: This report begins with a brief summary of the panel’s recommendations, followed by a more detailed analysis of its methodology, the findings of the comprehensive literature review, and a full presentation of the recommendations.
1,553 citations
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TL;DR: In this article, the authors evaluated the pharmacokinetics, efficacy and safety of a plasma-free recombinant FVIII concentrate, ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method, rAHF-PFM], in children < 6 years of age with severe hemophilia.
137 citations
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TL;DR: To the Editor: Inhibitors to factor IX (fIX) develop in approximately 1.5% to 3% of persons with severe hemophilia B and are commonly associated with the complete absence of fIX antigen due to large gene deletions or nonsense mutations.
119 citations
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TL;DR: By preventing new target joints, prophylaxis can lead to reduction in long‐term morbidity and a better quality of life despite increased central lines and higher factor usage.
Abstract: The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.
94 citations
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TL;DR: The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphyactic immune response.
Abstract: Haemophilia B is an X-linked recessive coagulopathy due to mutations in the factor IX gene. Occasionally, patients receiving factor IX replacement therapy develop inhibiting antibodies to the factor IX protein, and it has been recently documented that a subset of these patients have had anaphylactic responses to factor IX replacement therapy in association with the development of inhibiting antibodies. To determine the relationship between mutation type and the risk of anaphylaxis, eight unrelated patients from families in whom anaphylaxis had occurred were genotyped. The mutations were compared to those in 550 haemophilia B patients and to those in 276 patients with clinically severe disease. Individuals with complete gene deletions were found to be at greatest risk for anaphylaxis, with an estimated risk of 26% or greater. Anaphylaxis was less likely to occur in patients with protein truncation mutations or partial gene deletions and least likely to occur with missense mutations. Genotypes can help physicians and patients anticipate the likelihood of anaphylaxis, a potentially life-threatening complication of factor IX replacement therapy. The very high risk of anaphylaxis associated with a complete gene deletion suggests that the lack of expression of a partial protein product may predispose to anaphylaxis and/or that the absence of a closely linked, codeleted gene enhances the anaphylactic immune response.
81 citations
Cited by
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University of Washington1, University of Paris2, Queen Mary University of London3, McMaster University4, Cornell University5, University of Pennsylvania6, University of New South Wales7, Medical University of Vienna8, Sapienza University of Rome9, Scripps Research Institute10, Boston Children's Hospital11, University of Toronto12, University of Oklahoma Health Sciences Center13
TL;DR: An International Working Group of recognized expert clinicians convened a 2-day structured meeting to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response.
2,127 citations
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Queen Mary University of London1, National Health Service2, University of Toronto3, Manchester Royal Infirmary4, NewYork–Presbyterian Hospital5, University of New South Wales6, Hospital of the University of Pennsylvania7, University of Washington8, Boston Children's Hospital9, Hull York Medical School10, King's College London11, St James's University Hospital12, Scripps Research Institute13, Harvard University14
TL;DR: This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy.
1,902 citations
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TL;DR: Some of the key characteristics of protein therapeutics are overviewed, a new classification of these proteins according to their pharmacological action is suggested and this article summarizes the more than 130 protein therapeuticals used currently and suggests a new classifications.
Abstract: Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.
1,654 citations
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TL;DR: This review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of "front-line" therapy for ITP, the management of serious bleeding in patients withITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention.
1,601 citations
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TL;DR: The authors of this up-to-date review discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
Abstract: Immune thrombocytopenic purpura, which may lead to bleeding, is typically caused by antibodies directed against the platelet glycoprotein IIb/IIIa complex. Since the management of the disorder is different for children and adults, the authors of this up-to-date review provide separate sections on the two age groups. Along with advances in management, they also discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
1,255 citations