RESUMO
INTRODUCTION: Haemophilia A treatment with factor VIII concentrates requires frequent venipunctures; a central venous access device (CVAD) may be required to facilitate reliable venous access, especially in young children. While CVADs provide reliable venous access, complications such as infection and thrombosis may occur. AIM: The aim of this study was to assess CVAD use in the Canadian Hemophilia Primary Prophylaxis Study (CHPS), a single-arm, multi-centre prospective study whereby factor use is tailored to individual prophylactic need. METHODS: Participants received a tailored, escalating dose, prophylaxis regimen of increasing frequency of FVIII infusions: step-1: 50 IU kg(-1) once weekly; step-2: 30 IU kg(-1) twice weekly; and step-3: 25 IU kg(-1) on alternate days, according to their level of bleeding. CVAD insertion was at the discretion of the local health care team. Details regarding CVAD use during this protocol were analysed. RESULTS: Fifty six boys were enrolled, 21 required 25 CVADs due to difficult venous access. CVADs were inserted at a median age of 1.3 years (range: 0.6-2.1) and were removed at a median age of 8.7 years (range 6.3-11.8). Six participants experienced non-life threatening CVAD-complications, the most frequent being device malfunction requiring CVAD replacement (n = 4). Two boys were shown to have CVAD-associated thrombosis detected on routine imaging; one required removal due to infusion difficulties and the other was asymptomatic and did not require device removal. No CVAD-related infections were documented. CONCLUSION: Our study shows that the CHPS tailored prophylaxis regimen is associated with a decreased requirement for CVADs and with few device-related complications.
Assuntos
Cateteres Venosos Centrais , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Adolescente , Canadá , Cateteres Venosos Centrais/efeitos adversos , Criança , Pré-Escolar , Remoção de Dispositivo , Esquema de Medicação , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Trombose/etiologiaRESUMO
The objective of this study was to evaluate the inhibitor development (ID) in previously untreated patients (PUPs) with severe haemophilia A (FVIII ≤ 0.01 IU mL(-1) ). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7 years. Eligible patients had at least 20 exposure days (ED) or had developed an inhibitor. The odds ratio (OR) and 95% confidence intervals (95% CI) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A PUPs were studied. Thirty-four (34%) developed an inhibitor (24/34 of high titre). Inhibitors developed in 25/63 (40%) patients with a high-risk mutation. ID was most frequent in Aboriginals (86%). Dose intensity (IU kg(-1) day(-1) X number of ED) at first exposure to factor VIII (FVIII) was associated with a crude OR increase of 1.10 (95% CI: 0.99-1.23) with each increase of 100 dose-intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to FVIII concentrate were associated with a crude OR for ID of 7.63 (95% CI: 2.14-27.17) and 5.08 (95% CI: 1.11-23.31) respectively. ID according to FVIII concentrate used was: Advate (®) 18/50 (36%), Kogenate FS(®) or Helixate FS(®) 15/36 (42%), Wilate(®) 0/11 and Xyntha(®) 1/2. In multivariate analysis, Aboriginal ethnicity (OR = 11.69; 95% CI: 1.11-122.86) and haemarthrosis (OR = 4.49; 95% CI: 1.08-18.61) were statistically significant. The cumulative incidence of ID in severe haemophilia A PUPs was 34% and varied according to ethnicity, type of bleeding at first ED, type of FVIII product and dose intensity at first exposure.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Hemofilia A/epidemiologia , Hemofilia A/imunologia , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Canadá/epidemiologia , Pré-Escolar , Fator VIII/genética , Fator VIII/uso terapêutico , Seguimentos , Pesquisas sobre Atenção à Saúde , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Humanos , Incidência , Lactente , Recém-Nascido , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Mutação , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The incidence of intracranial haemorrhage (ICH) in von Willebrand disease (VWD) is not well documented. We describe our single centre experience regarding ICH in children with VWD and identify how such children presented and were managed. Thirty-three head trauma events leading to medical attention occurred in 24 of 153 children with VWD followed in our institution. In only 15 of these were computed tomography (CT) imaging studies performed; seven in children with type 1 VWD, one in a child with type 2N VWD and seven in children with type 3 VWD. In six of these 15 episodes an ICH was identified: two children with type 1 VWD, one child with type 2N VWD and three children with type 3 VWD. In two of the 6 cases an ICH was only confirmed following a second CT scan. Neurological symptoms, including vomiting (noted in all six), headache, irritability, lethargy and/or alteration in the level of consciousness were present in all children with confirmed ICH. In contrast vomiting, irritability and alterations in level of consciousness were never present in those children without confirmed ICH. All three children with type 3 VWD who experienced an ICH were commenced on long-term prophylaxis. ICH, although rare, does occur in children with VWD and particularly in children with type 3 VWD. A much larger cohort of patients with VWD experiencing an ICH is needed to make recommendations regarding treatment of such events, including the role of prophylaxis in patients with more severe forms of VWD.
Assuntos
Hemorragias Intracranianas/etiologia , Doenças de von Willebrand/complicações , Criança , Pré-Escolar , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Demografia , Feminino , Humanos , Lactente , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/terapia , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Doenças de von Willebrand/diagnóstico por imagemRESUMO
Hepatitis in children with haemophilia was historically most often associated with transfusion-transmitted infections. However, with the use of recombinant clotting factor concentrates, acquisition of such infections has now become rare. We studied the profile of hepatitis in North-American children with haemophilia in the modern era of safe blood products and excess childhood obesity. A total of 173 boys (<18 years) registered in the Pediatric Comprehensive Care Haemophilia Program were included in this retrospective study. Hospital records were reviewed for baseline data, serial height and weight measurements and serial alanine aminotransferase (ALT) levels. A body mass index (BMI) ranking was available for 170 boys, of whom 25 (14.7%, 95% CI 9.7-20.9%) were obese. The rate of obesity was higher in severe haemophilic boys. Compared with the general childhood population, the rate of obesity trended towards being higher in young haemophilic boys (2-5 years), but was similar in other age groups. A persistently high ALT (≥80 U L(-1) ) was documented in 5 boys and was associated with obesity. Three boys had clinical and imaging studies compatible with non-alcoholic fatty liver disease (NAFLD). Overweight and obesity are common among haemophilic boys, especially those who are younger and with severe disease. In this large group of haemophilic boys, chronic viral hepatitis was rare and NAFLD was a more common cause of liver disease. Overweight and obese haemophilic boys should be evaluated for NAFLD and interventional programmes should be designed to reduce the potential complications associated with obesity.
Assuntos
Hemofilia A/complicações , Hemofilia B/complicações , Hepatite/epidemiologia , Obesidade/epidemiologia , Adolescente , Fatores Etários , Alanina Transaminase/sangue , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Fígado Gorduroso/epidemiologia , Hemofilia A/enzimologia , Hemofilia A/fisiopatologia , Hemofilia B/enzimologia , Hemofilia B/fisiopatologia , Hepatite/complicações , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica , América do Norte/epidemiologia , Obesidade/complicações , Prevalência , Estudos RetrospectivosRESUMO
Type 3 Von Willebrand disease (VWD) is a rare, severe, autosomal recessive bleeding disorder. In our institution, we follow 17 children with type 3 VWD. We have observed a high prevalence of dental disease in these patients prompting us to undertake a retrospective review of our cohort of patients with type 3 VWD to catalogue the extent of their dental disease. Sixteen of these patients have been assessed by our dentistry department. Five children have undergone minor dental procedures (e.g. restorations, stainless steel crowns) and seven major procedures (e.g. dental extractions, pulpotomies and root canal treatments). These patients have collectively used 85,400 (ristocetin cofactor) IU of Humate-P on dental procedures alone. In addition to the considerable costs of factor are the cost of operating room time, dentists' costs, and the cost of other topical haemostatic agents (e.g. Tisseel) used during their dental procedures. As such there is considerable morbidity and cost from dental disease in these patients that is much higher than what is seen in patients with haemophilia or in the normal paediatric population. We speculate that the combination of these patients having a significant mucosal bleeding disorder together with various socioeconomic factors contribute to the significant degree of dental disease seen in this group of patients. We would suggest that better preventive dental care needs to be provided to these patients to avoid the considerable morbidity and very high burden of dental disease in type 3 VWD.
Assuntos
Saúde Bucal/normas , Doenças Dentárias/complicações , Doenças Dentárias/epidemiologia , Doença de von Willebrand Tipo 3/complicações , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Assistência Odontológica/normas , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics.
Assuntos
Hemofilia A/tratamento farmacológico , Vacinas contra Hepatite A/administração & dosagem , Hepatite A/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Hemofilia A/complicações , Humanos , Esquemas de Imunização , Lactente , Masculino , Guias de Prática Clínica como Assunto , Fatores de Risco , Adulto JovemAssuntos
Hemofilia A/prevenção & controle , Hemofilia A/terapia , Hemorragia/prevenção & controle , Hemorragia/terapia , Esportes , Doença de von Willebrand Tipo 3/prevenção & controle , Doença de von Willebrand Tipo 3/terapia , Adolescente , Éxons/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto/genética , Fator de von Willebrand/genéticaRESUMO
Surgery in infants and young children with haemophilia, when preceded by accurate diagnosis and accompanied by safe and effective factor prophylaxis, is not associated with a significant risk of haemorrhage. Haemophilic newborns undergoing circumcision or major surgery prior to diagnosis and in the absence of appropriate haemostatic prophylaxis remain as a concern. Inhibitor development has replaced haemorrhage as the major surgical complication in the developed world, largely because of the intensity of treatment used to secure haemostasis. For that reason only, essential surgery should be performed. Intracranial haemorrhage (ICH) during the neonatal period affects 3.5-4.0% of all haemophilia boys in countries with a good standard of health care, which is considerably (40-80 times) higher than expected in the normal population. Because of the high frequency of sporadic cases, ICH in the neonatal period can only be partially prevented by improved carrier diagnosis and counselling. Infections and thrombosis are the major serious complications of central venous lines. Large differences are seen in the frequency of these complications, the most plausible explanations are probably related to the protocol used for device care, the quality of education and the compliance of the users, an issue addressed in an on-going study.
Assuntos
Hemartrose/complicações , Hemofilia A/complicações , Hemorragias Intracranianas/prevenção & controle , Trombose/prevenção & controle , Cateterismo Venoso Central/métodos , Pré-Escolar , Circuncisão Masculina/efeitos adversos , Fator IX/uso terapêutico , Fator VIII/uso terapêutico , Testes Genéticos , Hemartrose/tratamento farmacológico , Hemartrose/cirurgia , Hemofilia A/tratamento farmacológico , Hemofilia A/cirurgia , Humanos , Lactente , Recém-Nascido , Hemorragias Intracranianas/epidemiologia , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Central venous catheters (CVCs) are often inserted into boys with hemophilia to secure venous access for factor prophylaxis and immune tolerance induction therapy. Complications associated with CVCs include catheter-related infections, local hemorrhage, and mechanical failure. Less frequently reported is CVC-related deep venous thrombosis (DVT). We conducted a prospective study to determine the frequency and outcome of this complication. METHODS: All boys (n = 16) with congenital hemophilia A or B with a CVC in place who were registered in the pediatric comprehensive care program at the Hospital for Sick Children, Toronto, were included in the study. They were prospectively assessed by imaging studies and clinical examinations for CVC-related DVT at two time-points, 2 years apart. Each boy was evaluated for inherited hypercoagulability. RESULTS: Eleven (69%) of the 16 boys had radiological evidence of DVT at the first evaluation and 13/16 (81%) at the second evaluation. In two boys there was improvement in the venogram findings at the second evaluation. None of the CVC-related DVTs completely resolved. Median age at the time of initial insertion of a CVC was 1.0 years (range 0.02-6.7 years). Median duration of CVC placement was 6.4 years (range 3.3-15.5 years). Only 4/13 boys with DVTs had clinical evidence of upper venous system obstruction. Only one boy, who did not develop a DVT, had a low protein C level. CONCLUSIONS: CVC-related DVTs occur in the majority of boys with hemophilia who have CVCs inserted for a prolonged period of time. Annual screening with imaging is recommended for boys with CVCs in place for >/= 3 years. Consideration should be given to removing CVCs as soon as peripheral venous access is feasible.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Hemofilia A/complicações , Trombose Venosa/etiologia , Criança , Pré-Escolar , Constrição Patológica/etiologia , Diagnóstico por Imagem , Saúde da Família , Hemofilia A/diagnóstico , Hemofilia A/terapia , Humanos , Incidência , Lactente , Estudos Longitudinais , Masculino , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Trombofilia/genética , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Inhibitors are rare in boys with mild hemophilia A (MHA; factor (F)VIII:C > 5%) but may arise following intense FVIII exposure, e.g. continuous infusion (CI). OBJECTIVES: To determine the impact of intense FVIII exposure in inhibitor formation in MHA at our institution and to compare this with previous reports. PATIENTS AND METHODS: We reviewed FVIII exposure and inhibitor development in boys (ages 0-18 years) with MHA followed at our institution from 1996 to 2001 and conducted a Medline search (1966-2002) on the experience of inhibitor development following intensive/CI exposure to FVIII. RESULTS: We identified 54 boys with MHA. Twenty-nine (54%) had been exposed to FVIII. Seven had received FVIII by CI. Four developed inhibitors; three high titer (at ages 10 years, 16 years and 17 years) and one low titer (at 1 month old). All four had received a CI of recombinant (r) FVIII of at least 6 days within 6 weeks of developing inhibitors. Baseline FVIII levels fell to < 1% in all cases and the three with high-titer inhibitors developed severe bleeding. Immune tolerance therapy (ITT) was attempted in two boys and was successful in one. Our literature search identified 35 cases (only four children) with MHA developing inhibitors following intense FVIII exposure often in the context of surgery. CONCLUSIONS: The incidence of inhibitors in our MHA population was 7.4%. If expressed according to exposure the incidence was significantly higher: 14% (4/29) for any exposure to FVIII and 57% (4/7) for exposure by CI. A prospective study to address whether CI is associated with an increased incidence of inhibitor development in MHA is warranted.
Assuntos
Fator VIII/imunologia , Hemofilia A/imunologia , Isoanticorpos/sangue , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Gerenciamento Clínico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Humanos , Tolerância Imunológica , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Definitive diagnosis of type 1 von Willebrand Disease (VWD) remains a problem. Provisional consensus guidelines for the diagnosis of definite and possible type 1 VWD were prepared by the Scientific Subcommittee on von Willebrand factor (VWF) of the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) during the 1996 annual meeting for the specific purpose of further evaluation in retrospective and prospective studies by a Working Party on Diagnostic Criteria (1996 Annual Report of the SSC/ISTH Subcommittee on VWF). In the first phase of this study, we compared 2 definitions of type 1 VWD. each with 3 criteria: significant bleeding history, laboratory investigations, and family history. Using the ISTH consensus guidelines for type 1 VWD definition, significantly fewer patients were diagnosed with definite type 1 disease as compared to our "in house" Hospital for Sick Children (HSC) criteria (4 vs. 31). While we recognize that the provisional ISTH consensus guidelines were not intended for clinical use, we believe that the results of our studies are of interest and will assist in any future refinements to the ISTH guidelines. In the second phase of this study, we investigated the utility of 2 new tests, a laboratory screening test and a functional test, for VWD in our well characterized, pediatric-based population. The Platelet Function Analyzer (PFA-100) provides an in vitro measure of primary hemostasis under conditions of high shear, using disposable cartridges containing collagen and either epinephrine or ADP. All tested subjects with types 2 or 3 VWD had prolonged PFA-100 closure times (CTs) with both cartridge types (n = 17) and prolonged bleeding times (n = 14). In subjects with definite type 1 VWD, 20/24 (83%) had prolonged CTs with the collagen/ADP cartridge (19/24 (79%) with collagen/epinephrine), compared with 7/26 (27%) with prolonged bleeding times. In subjects with definite types 1, 2, or 3 VWD, collagen/ADP CTs were abnormal in 37/41 subjects, giving an overall sensitivity of 90%. With this high sensitivity, the PFA-100 is a better screening test for VWD than the bleeding time. We also tested a VWF collagen-binding assay (VWF:CBA) as a functional test for VWF, in comparison with the more routinely-used ristocetin cofactor assay (VWF:RC0). The VWF:CBA is based on an ELISA technique, which has the potential to be more reproducible than the VWF:RC0. We found that the VWF:CBA detected 43/49 (88%) subjects with definite types 1, 2, or 3 VWD, performing as well as the VWF:RC0, that detected 42/48 (88%). We also showed that, used in conjunction with VWF antigen levels, the VWF:CBA may be useful in classification of VWD subtypes.
Assuntos
Doenças de von Willebrand/diagnóstico , Adolescente , Tempo de Sangramento , Testes de Coagulação Sanguínea/normas , Criança , Pré-Escolar , Colágeno/metabolismo , Dimerização , Eletroforese em Gel de Poliacrilamida , Saúde da Família , Feminino , Humanos , Lactente , Masculino , Peso Molecular , Testes de Função Plaquetária/instrumentação , Ligação Proteica , Kit de Reagentes para Diagnóstico/normas , Ristocetina/metabolismo , Sensibilidade e Especificidade , Doenças de von Willebrand/classificação , Fator de von Willebrand/análise , Fator de von Willebrand/química , Fator de von Willebrand/metabolismoRESUMO
OBJECTIVES: To examine the validity of a modified standard gamble (Mod SG) (nondeath baseline) by comparing these scores to SG (death baseline), time trade off (TTO), visual analog scale (VAS), Health Utilities Index (HUI), and Child Health Questionnaire (CHQ). METHODS: Respondents were parents of in-patients with cancer receiving chemotherapy and parents of children without cancer attending outpatient clinics. Construct validity was determined by comparing a priori hypotheses to actual correlations between measures. Discriminant validity was examined by anticipating that in-patients with cancer would have lower HRQL than outpatients. RESULTS: 85 families were included. Both Mod SG and SG were moderately correlated with TTO (r=0.50 and r=0.49; P<.01 for both). Both Mod SG and SG were moderately correlated with TTO (r=0.47 and r=0.05, P<0.002 for both). CONCLUSION: The Mod SG did not perform better than SG. Two nonoverlapping groups of HRQL measures were demonstrated.
Assuntos
Neoplasias/terapia , Pais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Hospitalização , Humanos , Lactente , Análise de Componente Principal , Reprodutibilidade dos Testes , Assunção de Riscos , Inquéritos e QuestionáriosRESUMO
Twenty-five central venous lines (two external 23 subcutaneous ports) were placed in 19 boys with haemophilia A (n = 17) or B (n = 2). The mean age of the boys was 4.9 years (range 0.2-15.3 years). The haemophilia was severe (factor level < 1%) in 18 boys and moderate (factor level 3%) in one. Three boys had circulating inhibitors and three were positive for human immunodeficiency virus (HIV)-1 antibody. Central venous lines were placed to facilitate intermittent factor replacement therapy (n = 6), long-term factor prophylaxis (n = 9), induction of an immune tolerance protocol (n = 2) or therapy for acquired immunodeficiency syndrome (AIDS)-related complications (n = 2). The ports remained in place for 15795 days (mean 687 days, range 11-2059 days). The frequency of port-related sepsis was 48% (11/23 ports in eight boys) or 0.7 port infections per 1000 patient days. Ports were removed from five boys with an unresolved infection (four with Staphylococcus aureus sepsis and one with Pseudomonas sp. sepsis). Other complications requiring port removal included a catheter tip placed too high in the venous system (n = 1), severe persistent pain associated with needle access of the port (n = 1) and a subclavian vein thrombosis (n = 1). Both the benefits and risks of a subcutaneous port should be considered when deciding whether to place this device in a very young child with haemophilia.
Assuntos
Cateterismo Venoso Central , Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Autoanticorpos/sangue , Bacteriemia/etiologia , Cateterismo Venoso Central/efeitos adversos , Criança , Pré-Escolar , Fator IX/uso terapêutico , Fator VIII/imunologia , Fator VIII/uso terapêutico , Soropositividade para HIV , HIV-1 , Hemofilia A/complicações , Hemofilia B/complicações , Humanos , Lactente , Masculino , Infecções por Pseudomonas , Infecções EstafilocócicasRESUMO
The most frequent indication for placement of a central venous access device in hemophiliacs is in very young boys (ages 1-2 years) with severe hemophilia who are started on a program of long-term factor prophylaxis designed to eliminate target joint bleeding and the development of chronic musculoskeletal disease. Although expensive, this strategy is extremely successful. It involves intravenous infusion of 25-40 factor units per kg on alternate days (minimum 3 times a week) for boys with severe hemophilia A, and twice a week for boys with severe hemophilia B. To facilitate this prophylaxis regimen some hemophilia clinics routinely recommend placement of a central venous access device; others, more concerned about associated complications such as sepsis, stress the importance of using peripheral veins wherever possible, with central access devices reserved for occasional, selected cases only. A decision to use such a device should only be made after discussion of the risks/benefits with parents (or guardians) and with patients if of an appropriate age. If such a system is to be used, we recommend that a totally implantable device (Port-A-Cath) be placed because of the lower risk of infection, and because totally implantable devices allow children to take part in activities such as swimming. Important complications include catheter-related sepsis, which may occur in 25% or more of devices over time and, much less frequently, catheter-related deep vein thrombosis.
Assuntos
Cateterismo Venoso Central , Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Infecções Bacterianas/etiologia , Cateterismo Venoso Central/efeitos adversos , Pré-Escolar , Fator IX/uso terapêutico , Fator VIII/uso terapêutico , Hemartrose/prevenção & controle , Humanos , Lactente , Masculino , Doenças Musculoesqueléticas/prevenção & controleRESUMO
BACKGROUND: Health-related quality of life can be measured by patients' health preferences (utilities or values). No method for measuring health state preferences has been standardized for children with arthritis or other musculoskeletal disorders (MSKDs). Such a method is needed for economic evaluations of current and new pediatric treatments. OBJECTIVES: 1) To assess the feasibility of utility measurements in children with MSKDs, 2) to test the validity of the Health Utility Index (HUI) for these children, 3) to assess whether rating scale values can be mathematically converted into meaningful standard gamble (SG) utilities, and 4) to study whether parents can act as proxies for their children with respect to health state preferences. METHODS: Eighty parents of children with MSKDs were consecutively sampled. Their children, if 8 years of age or older (n = 55), were studied concurrently. Utilities of current health states were obtained by using the SG and the HUI in random order. In addition, health state preferences were assessed using categorical and analog rating scales. Traditional nonutility measures of health status (the Childhood Health Assessment Questionnaire [CHAQ] and the Activities Scale for Kids [ASK]) were also completed. Intraclass correlation coefficients (ICCs) were calculated to assess concordance between the different utility measures and also between the ratings of the parents and their children. RESULTS: Children 8 years of age or older were able to express the strength of their health state preferences using the HUI and rating scales. Children older than 10 years of age were able to use the SG method. The health state utilities of the parents were higher than those of their children. The utilities varied widely depending on the elicitation method. The expected high agreement between the SG and the HUI was not found (ICC = 0.028 for parents, ICC = 0.016 for patients). Unlike the SG, the global utilities derived from the HUI agreed better with preferences derived from rating scales (ICC = 0.23-0.25) and correlated with traditional health status measures (with CHAQ, r = -0.56; with ASK, r = 0.46) both for parents and children. It was not possible to mathematically convert rating scale preferences into SG utilities. The SG utilities were unrelated to results from the rating scales, the CHAQ, and the ASK. Especially for parents, the SG utilities were very high, even when ratings of the other measures indicated poor health. CONCLUSIONS: Although it is possible to measure health utilities for children with MSKDs, the results are highly method dependent. The properties of the HUI in this population are more like those of the traditional health status measures rather than those of the SG. Preferences derived from rating scales, although easily performed, cannot readily be converted into SG utilities. Parents' ratings for their children are impaired by risk aversion.
Assuntos
Crianças com Deficiência/psicologia , Doenças Musculoesqueléticas/fisiopatologia , Satisfação do Paciente , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Doença Crônica/psicologia , Estudos de Viabilidade , Feminino , Humanos , Lactente , Masculino , Doenças Musculoesqueléticas/classificação , Pais/psicologia , Reprodutibilidade dos Testes , Perfil de Impacto da Doença , Inquéritos e QuestionáriosRESUMO
We conducted a review of a single institutional experience of patients with haemophilia presenting with suspected intracranial haemorrhage (ICH) who underwent computed tomographic (CT) neuro-imaging. We found that over a 9-year period (1996-2004) 43 patients with haemophilia presented 73 times with suspected ICH: 10 presented multiple times (range: 2-9 times). The median age at presentation was 3.5 years (range: 0.5-17). Preceding trauma occurred in most (62/73; 85%) episodes. ICH was confirmed in 11 of the 73 (16%) episodes in eight patients. Patients with severe haemophilia accounted for a disproportionate number of episodes of suspected (60/73; 82%) and of confirmed ICH (10/11; 91%). All ICH occurred in patients not on prophylaxis; five occurred in three inhibitor-positive patients. Altered consciousness at presentation was present in 10/11 (91%) cases of confirmed ICH but only in 5/62 (8%) (ICH-negative) episodes. The positive and negative predictive values of altered consciousness to predict/rule out an ICH was 67% and 98%, respectively. The following were associated with an increased risk of presenting with suspected ICH and of having a confirmed ICH: (i) having severe haemophilia; (ii) not being on prophylaxis; (iii) having an inhibitor; and (iv) presenting with an altered level of consciousness. Patients without any of these features may not need to undergo CT imaging when presenting with suspected ICH. Ideally a prospective study to evaluate this hypothesis should be conducted.
Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Fator VIII/uso terapêutico , Hemofilia A/complicações , Adolescente , Hemorragia Cerebral/etiologia , Pré-Escolar , Coleta de Dados/estatística & dados numéricos , Feminino , Humanos , Lactente , Tomografia Computadorizada por Raios XRESUMO
Although many patients with haemophilia may have exactly the same residual clotting factor level, the clinical disease phenotype may vary greatly. This variation may be related to different genetic mutations responsible for haemophilia, environmental influences and co-inheritance of polymorphisms affecting the coagulation system. The study of siblings with haemophilia offers the opportunity to examine additional factors, other than genetic mutation and environment that may impact on the clinical phenotype of haemophilia. We present the unusual case of haemophilia occurring in fraternal triplets. Each of the triplets had a slightly different pattern of bleeding and response to treatment.
Assuntos
Fator VIII/genética , Hemofilia A/genética , Fenótipo , Polimorfismo Genético/genética , Trigêmeos/genética , Pré-Escolar , Simulação por Computador , Fator VIII/farmacocinética , Humanos , Lactente , MasculinoRESUMO
Radiological imaging of joints in children with haemophilia is important to detect abnormalities, grade their severity and monitor the effects of treatment. Scoring systems for staging haemophilic arthropathy have been developed based on plain film or magnetic resonance imaging (MRI) findings. Radiographs alone may be inadequate for evaluating joint disease in children with haemophilia on prophylaxis while MRI may be difficult to access and require the child to be sedated. Sonography can be a useful complementary modality in the evaluation of haemophilic arthropathy that is readily available and does not require the child to be sedated. In this paper, we briefly review the current imaging scales available for the assessment of haemophilic arthropathy and present a systematic protocol for sonographic assessment of the knee and ankle in haemophilic children along with examples of findings in joint effusion/hemarthrosis, synovial hypertrophy and cartilage loss. Also, we correlate the ultrasound findings with the corresponding MRI images demonstrating the anatomic planes used for imaging acquisition. Sonography is a promising technique for the assessment of soft tissue changes which are the earliest findings in haemophilic arthropathy. Further investigation is required for evaluation of osteochondral changes given limitations of sonography in this regard and in minimizing operator dependency, especially if applied in multicentric clinical trials.
Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Hemartrose/diagnóstico , Hemofilia A/diagnóstico , Articulação do Joelho/diagnóstico por imagem , Ultrassonografia/métodos , Articulação do Tornozelo/patologia , Criança , Pré-Escolar , Humanos , Lactente , Articulação do Joelho/patologia , Índice de Gravidade de DoençaRESUMO
When a high titre inhibitor develops in a patient with haemophilia, attempts are made to eradicate it through immune tolerance induction therapy (ITI) involving the frequent and regular administration of factor, usually for months to years. ITI is successful in only two thirds of patients prompting investigators to explore alternate regimens to use in haemophiliacs failing conventional ITI. Rituximab is an anti-CD20 monoclonal antibody, which has shown promise in the treatment of B-cell-mediated disorders. We developed a protocol for the use of rituximab in haemophilia A (HA) patients failing conventional ITI or in those haemophiliacs where the likelihood of success of conventional ITI is poor. Patients receive 375 mg m(-2) of intravenous rituximab weekly for 4 weeks followed by monthly (up to 5 months) until inhibitor disappearance and establishment of normal FVIII pharmacokinetics (recovery and half-life). Patients are concurrently placed on recombinant FVIII (100 U kg(-1) day(-1)). We have placed five haemophiliacs (four children with severe HA, and one adult with mild HA) on this protocol. In three patients (two with severe HA and one with mild HA) inhibitors disappeared although in neither severe haemophiliac did FVIII pharmacokinetics completely normalize. The fourth patient had a significant drop in inhibitor titres although not a complete disappearance of the inhibitor. All four of these patients ceased bleeding following rituximab. The fifth patient had no response to rituximab. This non-responding patient was not placed on concurrent FVIII. Our five cases suggest that rituximab may hold promise in the eradication of inhibitors. Prospective randomized studies are required to determine the value of this agent in inhibitor management.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Hemofilia A/terapia , Fatores Imunológicos/administração & dosagem , Adolescente , Idoso , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Criança , Protocolos Clínicos , Esquema de Medicação , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Fator VIII/farmacocinética , Fator VIII/uso terapêutico , Hemofilia A/genética , Humanos , Tolerância Imunológica/imunologia , Fatores Imunológicos/imunologia , Imunoterapia/métodos , Masculino , Mutação , Rituximab , Resultado do TratamentoRESUMO
We report the case of a 10.5-year-old boy with severe haemophilia A (SHA) and inhibitors who presented with superior vena cava (SVC) obstruction while on immune tolerance induction (ITI) with daily recombinant factor VIII (rFVIII) and factor eight bypassing activity (FEIBA) (75 U kg(-1)) twice a week. The boy had a right-sided implanted central venous catheter. Imaging revealed a large occlusive thrombus in the SVC with all upper venous system drainage occurring through the azygos and collateral veins. Despite initial success with local thrombolytic therapy using recombinant tissue plasminogen activator, the thrombus persisted. Mechanical thrombolysis and angioplasty resulted in the successful removal of the thrombus and resolution of the SVC syndrome. Unfractionated heparin was used to prevent thrombus reformation/propagation. A work-up did not reveal any underlying genetic prothrombotic risk factors. The occurrence of such a profoundly symptomatic thromboembolism (TE) in a boy with SHA with inhibitors is unusual. A combination of risk factors, including the ongoing infusion of high doses of FVIII in the context of a disappearance of inhibitors together with the infusion of clotting factors known to be potentially thrombogenic, may place haemophilic patients on ITI (immune tolerance induction) at risk for this rare, life-threatening complication. The appropriate management of TEs in such a setting is unknown.