RESUMO
INTRODUCTION: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit. AIMS: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy. METHODS: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for ≥6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP). RESULTS: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year follow-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP. CONCLUSION: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.
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Fator IX , Hemofilia B , Adulto , Humanos , Masculino , Albuminas , Fator IX/uso terapêutico , Hemofilia B/tratamento farmacológico , Hemorragia/prevenção & controle , Hemorragia/tratamento farmacológico , Itália , Estudos Prospectivos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos RetrospectivosRESUMO
The protection of groundwater resources from non-point-source pollutants, such as those coming from agricultural practices, is the focus of several European Directives, including the Water Framework Directive and the Pesticide Directive. Besides the environmental goals to be reached by the single EU member state, these directives clearly underline the role of experts in supporting planners and public authorities to fulfil these objectives. This work presents a new web-based, freely-available dynamical tool, named the pesticide fate tool, developed within the geospatial Decision Support system (DSS), LandSupport, for the assessment of groundwater vulnerability, specific for type of pollutant. The tool is based on the extended transfer function model, specifically expanded to consider the transport of reactive solutes, such as pesticides. The work describes the tool implementation for three case studies, with different spatial scales and pedo-climatic conditions: Valle Telesina, IT, Marchfeld, AT, and Zala County, HU. Principal inputs of the tool are: soil physical and hydrological properties, climate, groundwater table depth, type of crops and related pesticides. Results of the model are shown through the LandSupport GUI both as coloured maps, representing the relative concentration of pesticide at the arrival to the water table at the end of the simulation period, and as cumulative charts of the solute arrival at the depth of interest. The three case studies are shown as examples of application of the LandSupport DSS in supporting the Water and Pesticides directives, demonstrating that it represents a valuable instrument for public authorities, environmental planners, as well as agricultural extension services. For example, large differences are shown by soils in filtering the tetraconazole (99.9% vs 76%), a fungicide used in viticulture, or different percentage of arrival (0.32% and 0,01%) to the groundwater table are shown for two herbicides (Tribenuron and Florasulam) largely used to control annual dicotyledonous weeds.
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Água Subterrânea , Praguicidas , Poluentes Químicos da Água , Agricultura , Monitoramento Ambiental , Praguicidas/análise , Solo , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The recombinant factor VIII (rFVIII)-IgG1 Fc fusion protein (rFVIII-Fc) was the first available extended half-life rFVIII, shown to prolong dosing intervals of individualised prophylaxis in patients with severe haemophilia A, maintaining low bleeding rates and unchanged or lower FVIII dose versus standard half-life (SHL) rFVIII. Few data are available about real-world experience with rFVIII-Fc, including criteria for patient switching from SHL products, follow up and prophylaxis optimisation. MATERIALS AND METHODS: A single-centre retrospective study was designed to review patients switched to rFVIII-Fc, based on individual needs, after pharmacokinetic (PK) assessment, according to routine clinical practice. In patients with adequate post-switch follow up, data about rFVIII-Fc prophylaxis were compared with those from the last 18-months SHL rFVIII prophylaxis. RESULTS: Of 25 candidates, 18 patients (15 severe, 3 moderate; aged 9-62 years; 3 with inhibitor history) started rFVIII-Fc regimens, with comparable FVIII weekly dose and reduced infusion frequency (mean -30%) in all 17 patients previously on SHL rFVIII prophylaxis thrice weekly or every other day. Over a mean 18-month follow up in 13 patients, compared with SHL products, further reduced infusion frequency (mean -40%; p<0.001; interval ≥4 days in 9 patients), improved treatment satisfaction (Hemo-sat questionnaires), significantly lower FVIII weekly dose and annual consumption (mean -12%; p=0.019), comparable bleeding rates and FVIII trough levels, and improved management of breakthrough bleeding were observed. von Willebrand Factor Antigen (VWF:Ag) correlated to PK variables and both had relationships with rFVIII-Fc weekly dose, increasing statistical significance over the follow-up period. No inhibitors or drug-related adverse events were recorded. DISCUSSION: In this real-world series of patients, a switch to rFVIII-Fc, based on careful assessment of clinical needs, PK testing and treatment monitoring, was able to optimise individual convenience, efficacy and costs of prophylaxis.
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Fator VIII , Hemofilia A , Hemorragia , Fragmentos Fc das Imunoglobulinas , Proteínas Recombinantes de Fusão , Adolescente , Adulto , Criança , Custos e Análise de Custo , Fator VIII/administração & dosagem , Fator VIII/economia , Fator VIII/farmacocinética , Seguimentos , Hemofilia A/sangue , Hemofilia A/tratamento farmacológico , Hemofilia A/economia , Hemorragia/sangue , Hemorragia/economia , Hemorragia/prevenção & controle , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/economia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/economia , Proteínas Recombinantes de Fusão/farmacocinética , Estudos RetrospectivosRESUMO
INTRODUCTION: Persons with haemophilia (PWH) experience recurrent joint bleeding which leads from early synovitis to irreversible joint damage. Pain strongly affects patients' quality of life, as PWH suffer from acute pain associated with haemarthroses and chronic pain due to arthritic and degenerative complications. AIM: To investigate pain issues among PWH and their treaters in Italy. METHODS: Persons with haemophilia and specialist physicians responded to a survey focused on pain characteristics, assessment, and management by phone call and online, respectively. RESULTS: One hundred and nineteen patients (76% severe haemophilia, 61% ≥18 years) and 44 physicians were involved. Pain was reported by 61% of PWH; among those who did not experience pain, 70% were children on prophylaxis. Patients described pain as chronic (71%), acute (69%) or postoperative (8%), and rated it as severe in 65% of cases. Clinicians reported lower percentages of patients with pain (46%), classified as chronic (58%), acute (33%) or postoperative (21%), half using specific scales. Pain was systematically investigated by treaters according to 36% of patients. Paracetamol was largely the most prescribed first-line pain therapy (89%), as well the most employed analgesic by PWH (51%), who also used non-steroidal anti-inflammatory drugs (24%), cyclo-oxygenase-2 inhibitors (21%) or opioids (26%). To manage pain, 61% of clinicians stated to collaborate with other specialists. Physiotherapy was often suggested but less frequently used by PWH. CONCLUSIONS: Pain is under-recognized and unsatisfactorily addressed by haemophilia treatment centre (HTC) clinicians, with discrepant management compared to PWH responses. Education in systematic pain assessment and multidisciplinary treatment and development of management guidelines are highly needed.
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Dor Crônica/etiologia , Hemofilia A/complicações , Manejo da Dor/métodos , Medição da Dor/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Hemofilia A/patologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Médicos , Inquéritos e Questionários , Adulto JovemRESUMO
Hemophilia is associated with a high financial burden on individuals, healthcare systems, and society. The development of inhibitors significantly increases the socioeconomic burden of the diseases. This study aimed to review and describe the burden of hemophilia with inhibitors, providing a reference scenario to assess the impact of new products in the real word. Two systematic literature reviews were performed to collect data on (i) health economics and (ii) health-related quality of life evidences in hemophilic patients with inhibitors. The costs associated with patients with hemophilia and inhibitors are more than 3 times greater than the costs incurred in those without inhibitors, with an annual cost per patient that can be higher than 1 000 000. The costs of bypassing agents account for the large majority of the total healthcare direct costs for hemophilia treatment. The quality of life is more compromised in patients with hemophilia and inhibitors compared to those without inhibitors, in particular the physical domains, whereas mental domains were comparable to that of the general population. The development of an inhibitor has a high impact on costs and quality of life. New treatments have the potential to change positively the management and socioeconomic burden of hemophilia with inhibitors.
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Efeitos Psicossociais da Doença , Hemofilia A/epidemiologia , Hemofilia B/epidemiologia , Coagulação Sanguínea , Custos de Cuidados de Saúde , Hemofilia A/sangue , Hemofilia A/imunologia , Hemofilia A/terapia , Hemofilia B/sangue , Hemofilia B/imunologia , Hemofilia B/terapia , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Qualidade de Vida , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Joint hemorrhages represent the most common type of bleeding episode in persons with hemophilia, and recurrent hemarthrosis triggers chronic arthropathy, which is the most frequent chronic complication in these patients. In recent years, in the frame of a comprehensive care approach, a growing attention has been given to the periodic assessment of the joint status in hemophilia patients with the aim to identify early arthropathic changes and to prevent the development of a clinically overt arthropathy. Besides clinical examination, X-ray and magnetic resonance imaging (MRI) are currently used to evaluate joint status and to monitor the disease progression in hemophilia. Considering the limitations of X-ray and MRI, growing interest has been given to ultrasound (US) as a possible tool to assess joint status and identify early arthropathic changes in hemophilia patients. In the present review, we summarize major literature evidence on the use of joint US for the evaluation of markers of disease activity (joint effusion and synovial hypertrophy) and of degenerative damages (osteochondral changes) in patients with hemophilia. On the whole, being able to identify the presence of intra- or extra-articular fluid, US examination is the fastest and most reliable technique to identify acute conditions, such as hemarthrosis. In addition, the information on joint involvement provided by US in the patient follow-up may influence treatment decisions on a personalized basis. The use of US as part of a routine clinical examination by hemophilia experts may optimize the diagnostic workflow, avoiding additional costs and long waiting lists for patients referred to imaging departments. In the frame of a comprehensive care approach, US might represent a strategy to early detect and monitor synovial hypertrophy and osteochondral changes in hemophilia, thus extending the clinical examination and helping identify joints to be studied with a second-level examination such as MRI.
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Hemofilia A , Hemorragia , Artropatias , Ultrassonografia , Hemofilia A/complicações , Hemofilia A/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Artropatias/diagnóstico por imagem , Artropatias/etiologia , Membrana Sinovial/diagnóstico por imagem , Estados UnidosRESUMO
BACKGROUND: In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. OBJECTIVES: To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. MAIN RESULTS: Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 µg/kg) was compared with a low-dose regimen (35 µg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.
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Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Hemostasia Cirúrgica/métodos , Procedimentos Cirúrgicos Operatórios , Extração Dentária , Ácido Aminocaproico/uso terapêutico , Fator VIIa/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/uso terapêutico , Ácido Tranexâmico/uso terapêuticoRESUMO
Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII) prophylaxis initiated in adolescent or adult patients with severe haemophilia A. The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on-demand treatment in patients aged 12 to 55 years with severe haemophilia A. The annual number of joint bleeding episodes (primary endpoint), total bleeding episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5-year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a significantly lower number of joint bleeding episodes vs the on-demand group (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older patients, respectively; p=0.0043). Results were similar for total bleeding episodes. Prophylaxis was associated with significantly fewer target joints (p< 0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required significantly higher FVIII product consumption. The POTTER study is the first prospective, controlled trial documenting long-term benefits of late secondary prophylaxis in adolescents and adults with severe haemophilia A. The benefits of reduced bleeding frequency, improved joint status, and HRQoL may offset the higher FVIII consumption and costs.
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Fator VIII/administração & dosagem , Hemartrose/prevenção & controle , Hemofilia A/tratamento farmacológico , Hemostáticos/administração & dosagem , Adolescente , Adulto , Fatores Etários , Criança , Análise Custo-Benefício , Esquema de Medicação , Custos de Medicamentos , Fator VIII/efeitos adversos , Fator VIII/economia , Hemartrose/sangue , Hemartrose/diagnóstico , Hemartrose/economia , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemofilia A/economia , Hemostáticos/efeitos adversos , Hemostáticos/economia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The authors assessed the operating safety physical parameters of a bipolar radiofrequency device for aesthetic purposes. According to both Italian and EU guidelines, the authors considered: magnetic field environmental emission levels, electricity induced in the opertator's limbs, operator's exposure and radiofrequency specific absorbance rate (SAR) in treated tissues. Measurements were carried out with isotropic sensors and an inductive current indicator. Results pointed out excellent safety levels regarding environment, operators and patients as well, although such radiofrequency equipment cannot be used on patients with pacemakers, neurostimulators and other vital function controlling devices.
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Campos Eletromagnéticos/efeitos adversos , Exposição Ocupacional/análise , Dispositivo de Identificação por Radiofrequência , Desenho de Equipamento , Segurança de Equipamentos , União Europeia , Guias como Assunto , Humanos , Itália , Medicina do Trabalho , Reprodutibilidade dos Testes , Medição de Risco , Fatores de TempoRESUMO
Hemophilias are the most known inherited bleeding disorders. The challenges in the management of hemophilic children are different from those in adults: prophylaxis regimen removed the hallmark of crippling disease with lifelong disabilities; individualized regimens are being implemented in order to overcome venous access problems. Presently, at least in high-income countries, advances in treatment of hemophilia resulted in continuous improvement of the patients' quality of life and life expectancy. Inhibitors remain the most severe complication of hemophilia therapy. The treatment' compliance is the key to achieve a successful management. The patient, his family, the medical and psychological team are the players of a comprehensive care system. The current management of hemophilic children is the example of huge resource investments enabling long-term benefits in particular quality of life as a primary objective of the healthcare process.
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Hemofilia A/terapia , Qualidade de Vida , Criança , Pré-Escolar , Análise Custo-Benefício , Atenção à Saúde/economia , Gerenciamento Clínico , Fator IX/administração & dosagem , Fator IX/genética , Fator IX/metabolismo , Fator VIII/administração & dosagem , Fator VIII/genética , Fator VIII/metabolismo , Hemofilia A/sangue , Hemofilia A/complicações , Hemofilia A/economia , Hemofilia A/prevenção & controle , Humanos , Qualidade de Vida/psicologia , Fatores de RiscoRESUMO
INTRODUCTION: Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. MATERIAL AND METHODS: The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. RESULTS: In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. CONCLUSIONS: The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.
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Envelhecimento , Transtornos Herdados da Coagulação Sanguínea , Redes Comunitárias/economia , Redes Comunitárias/organização & administração , Modelos Organizacionais , Fatores Socioeconômicos , Transtornos Herdados da Coagulação Sanguínea/economia , Transtornos Herdados da Coagulação Sanguínea/terapia , Redes Comunitárias/normas , Efeitos Psicossociais da Doença , Feminino , Humanos , Itália , MasculinoRESUMO
The assessment and monitoring of liver fibrosis (LF) is a key issue in the management and definition of prognosis of patients with chronic hepatitis C (CHC). In this respect, despite recognized limitations (invasive nature, sampling errors, interobserver variability, nondynamic evaluation of LF), liver biopsy is traditionally considered the reference standard. These limitations stimulated the search for noninvasive approaches for the assessment of LF, particularly attractive in patients with hemophilia and other congenital bleeding disorders (CBD). In patients with congenital bleeding disorders (CBD), who often suffer from CHC because of the past use of nonvirally inactivated plasma-derived products, the risk of bleeding hamper to routinely obtain histological data for LF staging. A variety of methods have been proposed and, in some cases, validated in patients with CHC and other liver diseases, including biomarkers directly or indirectly associated with LF, often combined in scores or algorithms, and the more recently developed physical approaches, evaluating the properties of the liver parenchyma with instrumental techniques studying the propagation of specific signals, that is, transient elastography (TE), acoustic radiation force impulse imaging elastography, and magnetic resonance elastography. This review will describe the available strategies for noninvasive assessment of LF, with more details on the latter promising instrumental approaches. Moreover, although lacking of validation against liver biopsy, recent studies extending the use of noninvasive methods (particularly TE) in the setting of patients with CBD will be discussed.
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Transtornos da Coagulação Sanguínea/patologia , Transtornos da Coagulação Sanguínea/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Transtornos da Coagulação Sanguínea/congênito , Humanos , Cirrose Hepática/sangue , PrognósticoRESUMO
Recurrent joint bleeding leading to progressive musculoskeletal damage (hemophilic arthropathy), in spite of on-demand replacement with deficient factor concentrates, is the clinical hallmark of severe hemophilia A and B (i.e., the congenital deficiencies of coagulation factors VIII and IX with circulating levels <1 IU/dL). Fifty years of clinical experience, which began in Northern Europe and then initiated in other European countries and in North America, up to the recent randomized clinical trials, have provided definitive evidence that preventing bleeding from an early age through long-term regular prophylactic concentrate infusions limits the adverse clinical consequences of arthropathy and its complications in the quality of life of hemophilic children. Primary prophylaxis started after the first joint bleed and/or before the age of 2 is now the evidence-based, first-choice treatment in severe hemophilia. Interestingly, recent data also suggest a role for early prophylaxis in preventing inhibitor development, the most serious complication of hemophilia therapy. Secondary prophylaxis is aimed to avoid (or delay) the progression of arthropathy. The earlier the treatment is started, the better the outcomes in joint status and quality of life. Although prophylaxis has radically transformed the natural history of severe hemophilia, relevant barriers to its implementation and diffusion remain. Beyond the obvious economic constraints and problems with venous access and long-term adherence, uncertainties regarding the optimal prophylaxis regimen require further evaluation in prospective studies to optimize approaches based on definite outcome measures and cost-effectiveness/cost-utility analyses. Scientific evidence, current clinical strategies, and open issues of prophylaxis in children with hemophilia will be addressed in this review.
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Hemofilia A/prevenção & controle , Adolescente , Criança , Pré-Escolar , Hemofilia A/terapia , Humanos , Lactente , Qualidade de VidaAssuntos
Fator IX , Fator VIII , Hemofilia A , Hemofilia B , Fator IX/administração & dosagem , Fator IX/economia , Fator VIII/administração & dosagem , Fator VIII/economia , Feminino , Hemofilia A/economia , Hemofilia A/prevenção & controle , Hemofilia B/economia , Hemofilia B/prevenção & controle , Humanos , Itália , Masculino , Inquéritos e QuestionáriosRESUMO
A four-decade clinical experience and recent evidence from randomised controlled studies definitively recognised primary prophylaxis, i.e. the regular infusion of factor concentrates started after the first haemarthrosis and/or before the age of two years, as the first-choice treatment in children with severe haemophilia. The available data clearly show that preventing bleeding since an early age enables to avoid or reduce the clinical impact of muscle-skeletal impairment from haemophilic arthropathy and the related consequences in psycho-social development and quality of life of these patients. In this respect, the aim of secondary prophylaxis, defined as regular long-term treatment started after the age of two years or after two or more joint bleeds, is to avoid (or delay) the progression of arthropathy. The clinical benefits of secondary prophylaxis have been less extensively studied, especially in adolescents and adults; also in the latter better outcomes and quality of life for earlier treatment have been reported. This review summarises evidence from literature and current clinical strategies for prophylactic treatment in patients with severe haemophilia, also focusing on challenges and open issues (optimal regimen and implementation, duration of treatment, long-term adherence and outcomes, cost-benefit ratios) in this setting.
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Coagulantes/administração & dosagem , Hemartrose/prevenção & controle , Hemofilia A/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Coagulantes/economia , Análise Custo-Benefício , Esquema de Medicação , Custos de Medicamentos , Medicina Baseada em Evidências , Custos de Cuidados de Saúde , Hemartrose/economia , Hemartrose/etiologia , Hemofilia A/complicações , Hemofilia A/economia , Humanos , Lactente , Adesão à Medicação , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Starting from the clinical observations that moderate haemophiliacs experienced only few bleeding episodes and rarely developed significant joint deterioration (haemophilic arthropathy), and the pioneer experience in Sweden, prophylaxis (i.e. the regular and long-term administration of clotting factor concentrate in order to prevent bleeding) has been practiced for more than forty years in severe haemophilia and is currently recommended as the first choice of treatment by the World Health Organisation and World Federation of Hemophilia and by many national medical/scientific organizations. Observational studies clearly established the superiority of prophylaxis over on-demand treatment in reducing the risk of arthropathy, also showing that starting prophylaxis earlier in life and after very few joint bleeds was associated with better joint outcomes, and led to the current definitions of primary (started before the age of 2 yrs and after no more than one joint bleed) and secondary prophylaxis. More recently, evidences from randomized trials, which were previously lacking in this setting, were also provided. This review summarizes available data from which current clinical practice of primary (and early secondary) prophylaxis in children with severe haemophilia was drawn. Open issues concerning optimal regimens and barriers to the implementation of prophylaxis are also discussed.