Increased prevalence of inhibitors in Hispanic patients with severe haemophilia A enrolled in the Universal Data Collection database
ABSTRACT Neutralizing inhibitors develop in 20-30% of patients with severe factor VIII (FVIII) deficiency. It is well established that Blacks have a higher prevalence of inhibitors than Whites. This is the first study to definitively demonstrate increased inhibitor prevalence in the Hispanic population. We compared inhibitor prevalence among various racial and ethnic groups in a cross-sectional analysis of 5651 males with severe haemophilia A that participated in the Universal Data Collection project sponsored by the Centers for Disease Control and Prevention. We used logistic regression analysis to control for potential confounding variables. We assigned as Hispanic those participants who were white and labelled themselves Hispanic. The prevalence of high-titre inhibitors in the Hispanic participants was 24.5% compared to 16.4% for White non-Hispanic patients (OR 1.4, 95% CI 1.1, 1.7). Possibilities as to the underlying cause of increased inhibitor prevalence in minority ethnic populations include polymorphisms in the FVIII molecule, HLA subtypes and differing inflammatory responses. A better understanding may lead to tailored treatment programmes, or other therapies, to decrease or prevent inhibitor development.
SourceAvailable from: Mehdi Osooli
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ABSTRACT: Congenital haemophilia A and B are genetic disorders affecting factor VIII and factor IX production, respectively. Factor replacement is the only effective treatment for these deficiencies, but a patient's immune system can develop inhibitory antibodies which bind and interfere with the function of the replaced factor in a variety of ways. The main treatment goal for patients with inhibitors is to induce immune tolerance to the injected factor. If not successful, a different treatment termed bypass therapy is needed to treat bleeds. The goal of this review is to demonstrate the usefulness of haemophilia registries as information sources to supplement available evidence regarding predictors of inhibitor development and immune tolerance induction (ITI) outcomes.In this systematic review, relevant keywords were used to search online academic databases during February 2014. Inclusion criteria were original publication and data obtained from a haemophilia or ITI registry with a minimum of 30 patients. A data collection form was created to extract information from selected manuscripts. Titles, abstracts and then full texts were screened to determine the eligibility of reports for this review.Eleven manuscripts from nine registries were determined eligible and included in the study. Registries have reported on some core variables, but are inconsistent in reporting less practiced predicting variables. Variables that may affect inhibitor and ITI outcomes were each divided into two categories: patient characteristics (such as age and family history) and treatment-related variables (including exposure days, treatment duration and dose).It is recommended that, in addition to exploratory hypothesis testing, a minimum set of variables should be collected and reported by registries. International collaboration and well-designed prospective registries are of major importance to advance this field in order to determine inhibitor risks and ITI outcomes and facilitate the development of new treatments.This article is protected by copyright. All rights reserved.Journal of Internal Medicine 08/2014; 277(1). DOI:10.1111/joim.12301 · 5.79 Impact Factor
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ABSTRACT: A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.Indian Journal of Hematology and Blood Transfusion 12/2014; 30(4):356-363. DOI:10.1007/s12288-014-0342-z · 0.23 Impact Factor