RESUMO
OBJECTIVE: To investigate a family with factor VII (FVII) deficiency from Argentina. PATIENTS AND METHODS: The proposita is a 14-year-old girl who presented with a mild to moderate bleeding tendency. Menorrhagia is controlled with periodical administration of small doses of recombinant FVII concentrate. The mother of the proposita has a similar bleeding tendency. RESULTS: FVII activity in both patients was 20% of normal; FVII antigen was 35% of normal. Molecular biology investigation revealed that the proposita was compound heterozygote between Thr384Met and Arg413Gln. The mother had the same mutations. This was due to the fact that the father of the proposita and her maternal grandfather both carried, in spite of no relation, the same mutation, namely Arg413Gln. CONCLUSIONS: The identical defect which presented in the propositaand her mother could be explained by the genetic analysis of the father and maternal grandfather of the proposita who happened to have the same mutation (Arg413Gln).
Assuntos
Substituição de Aminoácidos , Deficiência do Fator VII/diagnóstico , Deficiência do Fator VII/genética , Fator VII/genética , Heterozigoto , Mutação , Fenótipo , Adolescente , Adulto , Argentina , Testes de Coagulação Sanguínea , Análise Mutacional de DNA , Deficiência do Fator VII/sangue , Fator VIIa/administração & dosagem , Feminino , Estudos de Associação Genética , Humanos , LinhagemRESUMO
INTRODUCTION: Haemophilic pseudotumour (HP) is an encapsulated haematoma in patients with haemophilia (PWH) which has a tendency to progress and produce clinical symptoms related to its anatomical location. AIM: To show the experience of one surgeon who has been using mini-invasive technique to treat pseudotumours of limbs in PWH with and without inhibitors at one centre for 28 years. MATERIALS AND METHODS: Thirty-three patients with 39 HP were treated. All patients had haemophilia A. Twenty-four patients had no inhibitors (72.8%), and 9 had inhibitors (27.2%). The mean follow-up was 16 years (1-25). All patients had x-rays and MRIs. All of them received Buenos Aires protocol as conservative treatment for 6 weeks. MRIs were repeated after 6 weeks' treatment to assess response to treatment. Surgery was performed in patients who did not respond to conservative treatment. RESULTS: After Buenos Aires protocol, four pseudotumours did not shrink (10.24%), 33 (84.61%) shrank, and two (5.12%) healed. Thirty-seven pseudotumours had surgery, 35 pseudotumours (94.59%) healed with minimally invasive treatment, and two did not heal (5.41%). No infection was observed with this treatment. The mortality rate for the series was 0%. CONCLUSION: The minimally invasive treatment of pseudotumours was effective in 95% of the cases and resulted in no mortality in this series after 28 years.
Assuntos
Extremidades/patologia , Hematoma/cirurgia , Hemofilia A/patologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adolescente , Adulto , Criança , Coagulantes/administração & dosagem , Coagulantes/uso terapêutico , Tratamento Conservador/métodos , Extremidades/diagnóstico por imagem , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Hematoma/tratamento farmacológico , Hemofilia A/complicações , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Radiografia/métodos , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Despite the increased worldwide awareness, over the last decade, of the platelet-type von Willebrand Disease (PT-VWD), many uncertainties remain around this rare platelet bleeding disorder. This report aims to correctly identify and study the phenotype of new patients and highlights the diagnostic and therapeutic challenges this disease remains to pose. We describe four PT-VWD cases confirmed by genetic analysis in which either the diagnosis and/or the treatment posed challenge. We provide the details of the clinical presentation, laboratory analysis, and the treatment and the responses in each case. We show that in addition to type 2B VWD, PT-VWD can be misdiagnosed as idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and unexplained gestational thrombocytopenia. The disease can be diagnosed as early as 1 year of age and with phenotypically normal parents. Bleeding in some patients can be managed successfully using Humate P and DDAVP combined with tranexamic acid with no significant thrombocytopenia. We provide for the first time an evidence of an efficient response to rFVIIa in PT-VWD. Anaphylactic reaction to VWF preparations may be related to PT-VWD and the development of HLA antibodies is not uncommon. Progressive thrombocytopenia with normal VWF levels can be seen with PT-VWD and the platelet count was normalized at 2.5 weeks postpartum in one case. We conclude that these studies represent a record of clinical observations/interventions that help improve diagnoses/management of PT-VWD, highlight the variations in age and clinical presentations, laboratory diagnostic approaches, the importance of genetic testing for accurate diagnosis and consideration of therapeutic alternatives.
Assuntos
Desamino Arginina Vasopressina/administração & dosagem , Fator VIII/administração & dosagem , Fator VIIa/administração & dosagem , Hemorragia , Ácido Tranexâmico/administração & dosagem , Doenças de von Willebrand , Adolescente , Pré-Escolar , Quimioterapia Combinada/métodos , Feminino , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/tratamento farmacológico , Humanos , Recém-Nascido , Masculino , Proteínas Recombinantes/administração & dosagem , Doenças de von Willebrand/sangue , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológicoRESUMO
INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del Facto VII recombinante en el manejo de pacientes con diagnóstico de Hemofilia A severa, con presencia de inhibidores y que presentan o estén en riesgo de presentar evento agudo de sangrado o hemorragia, con el objetivo de prevenir muerte por sangrado no controlado. Aspectos Generales: La hemofilia es un desorden hematológico congénito ligado al cromossoma X. Se han identificado dos tipos principalmente, la Hemofilia A que es causado por deficiencia de factor de coagulación VIII (FVIII) y la Hemofilia B que es causado por deficiencia de factor de coagulación IX (FIX). La deficiencia de estos factoes es el resultado de mutaciones en los genes de los factores de coagulación respectivos. Tecnología Sanitaria de Interés: Factor VII Recombinante Activado-RFVIIA (Novoseven - Marca Registrada): El RFVIIA es un glicoproteina dependiente de la vitamina K que consiste em 406 residuos de aminoácidos (MW 50K Dalton). Es estructuramente similar al factor VIIa derivado de plasma hmano y actúa de manera semejante al factor VII en la cascada de coagulación. Debido a que el factor VII actúa directamente sobre el factor X independientemente del facto VIII y IX, este medicamento puede ser usado en pacientes con hemofilia que han desarrollado inhibidores a los factores VII oIX. METODOLOGIA: Estratégia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de Factor VII recombinante activado con diagnóstico de Hemofilia A severa, con presencia de inhibidores altos respondedores definido por presentar una alta respuesta (>= 5 unidades Bethesda UB), que presentan o estén en alto riesgo de presentar evento agudo de sangrado o hemorragia y que haya usado aPCC previamente. RESULTADOS: Se realizó la búsqueda bibliografica y de evidencia cientifica para el sustento del uso del Factor VII recombinante activado en pacientes con Hemofilia A severa con titulos elevados de inhibidores, que sean altos respondedores (>= 5 unidades Bethesda UB), que tengan o estén en alto riesgo de presentar evento agudo de sangrado y que hayan usado aPCC previamente. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se ha encontrado escasa evidencia que muestre que facto VII recombinante activado (rFVIIa) ofrezca beneficios para los pacientes con diagnóstico de hemofilia A severa con presencia de inhibidores y con alto riesgo de hemorragia de evento agudo de sangrado o hemorragia que hayan usado el concentrado de complejo protrombínico activado (aPCC). La evidencia que respalda esto uso de rFVIIa es aún muy limitada, se establece que el efecto de rFVIIa se evaluará con los datos de los pacientes que los hayan recibido por el periodo de vigencia de este Dictamen, para determinar el impacto de su usi en los desenlaces de interés de este Dictamen. Esta información será tomada en cuenta en la reevaluación de este medicamento para efectos de un nuevo dictamen al terminar la vigencia del presente Dictamen Preliminar.
Assuntos
Humanos , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Fator VIIa/administração & dosagem , Hemorragia/tratamento farmacológico , Protrombina/efeitos adversos , Fatores de Risco , Avaliação da Tecnologia Biomédica , Resultado do TratamentoRESUMO
Secondary prophylaxis with rFVIIa has been the subject of several publications in the past few years. However, there is no general consensus on how this treatment should be put into practice, as publications have been very heterogeneous in the dosing schedule they report. Furthermore, the mechanism of action of rFVIIa and its short half life have been used as arguments against its role in prophylaxis. There have been a series of recent publications that show that rFVIIa can traffic through the intact endothelium and be stored in the subendothelium of several organs for a prolonged period of time. In order to consensuate the role of rFVIIa in prophylaxis, a group of experts from Argentina, resumed available information regarding pharmacology and clinical experience with this treatment, and developed a series of recommendations to use this drug in the prophylaxis setting.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Coagulantes/administração & dosagem , Fator VIIa/administração & dosagem , Hemofilia A/prevenção & controle , Hemorragia/prevenção & controle , Argentina , Relação Dose-Resposta a Droga , Esquema de Medicação , Medicina Baseada em Evidências , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Resultado do TratamentoAssuntos
Humanos , Feminino , Gravidez , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/terapia , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/terapia , Complicações Hematológicas na Gravidez , Diagnóstico Precoce , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Hemostasia , Transfusão de Sangue/métodosRESUMO
BACKGROUND: Antiplatelet drugs constitute the therapy of choice for acute coronary syndromes, but bleeding can be a side-effect requiring treatment. Restoration of normal platelet activity is also mandatory before urgent surgery. This study investigated: (a) whether a regimen of aspirin or clopidogrel plus aspirin significantly inhibited platelet thrombin generation (TG); and (b) the reversal of this inhibition by recombinant activated factor VII (rFVIIa). METHODS AND RESULTS: TG was evaluated by the lag time, time to peak, peak of TG, and area under the curve after 35 min of assay (AUC(0 --> 35 min)). These measures were examined by the calibrated automated thrombography method in 22 healthy volunteers, 22 volunteers after a 100 mg day(-1) aspirin intake (200 mg first day) for 5-7 days, and 22 healthy volunteers after aspirin 100 mg day(-1) (200 mg first day) plus clopidogrel 75 mg day(-1) (300 mg first day) for 4-7 days. The TG parameters were measured under basal conditions and after platelet stimulation by sodium arachidonate (AA), adenosine 5'-diphosphate (ADP), collagen and rFVIIa in normal non-aspirinated as well as in vivo aspirinated platelet-rich plasma (PRP) or aspirin plus clopidogrel PRP. Lag time was shorter (P < 0.05), and peak of TG and AUC(0 --> 35 min) were significantly greater (P < 0.01 for both), in PRP activated with ADP, collagen, AA or FVIIa than in non-activated PRP from normal subjects. Both non-activated PRP and activated PRP prepared from platelets obtained from volunteers after aspirin intake showed significant prolongation of the time parameters but there was less effect on peak of TG and AUC(0 --> 35 min). For most parameters, aspirin plus clopidogrel administration showed to be more effective compared with the effect obtained by aspirin alone. When rFVIIa was added to ASA-PRP or ASA + Clop PRP, lag time (P < 0.001 for all) and time to peak (P < 0.001-0.017) were significantly shortened, indicating that rFVIIa reverses the inhibitory effect of these anti-aggregating agents. CONCLUSION: Platelets activated by AA, ADP, collagen or FVIIa triggered TG. This effect was inhibited by aspirin plus clopidogrel, suggesting an additional benefit of this drug combination for preventing thrombosis. rFVIIa reverses the inhibitory effect of aspirin or aspirin plus clopidogrel, and could be useful for bleeding complications or when acute surgery is needed during treatment with these antiplatelet drugs.