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Hemophilia A is an X-linked hereditary disorder with a predilection for men. A worldwide incidence of 1 in 5 000 inhabitants is estimated. Currently, there is no curative treatment, which can lead to the development of multiple complications. However, abdominal presentations related to acute abdomen are uncommon and require surgical treatment. Similar cases are related to psoas muscle hematoma and hemophilic pseudotumors. We presented a 25-year-old male diagnosed with hemophilia A with acute abdominal pain and peritoneal irritation signs. After evaluation, we decided to perform a laparotomy, which reported a hematoma in the right mesocolon from the ileocecal valve to the hepatic flexure with right colic artery disruption. After seven days, he was discharged due to clinical improvement, and we indicated an outpatient general surgery follow-up. Acute abdomen caused by a retroperitoneal hematoma in patients with hemophilia is uncommon. Therefore, its management is still controversial. We concluded that a surgical approach might reduce the risk of complications in patients with poor clinical courses.
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Introduction Treatment of hemophilia A in Brazil is offered to all patients at no cost. However, several unmet medical needs exist. Method In this study, we applied the Delphi method to discuss with seven hemophilia A specialists the challenges that patients and the health system face regarding hemophilia A treatment and opportunities for improvement. Results A consensus was obtained regarding the number of weekly infusions and patient adherence to treatment. The bleeding profile, unfavourable pharmacokinetics (PKs), low adherence and high daily activity were patient profiles that would benefit from using the extended half-life (EHL) recombinant factor VIII (rFVIII). The advantages of treatment with the EHL rFVIII were the lower number of infusions per week, which could increase patient adherence and decrease the risk of bleeds, due to a more constant plasma level, a lower value. Additionally, the EHL rFVIII could improve quality of life, especially in patients with high daily activity, such as adolescents and young adults. The panelists mentioned that EHL rFVIII, if available, could be offered first to the priority group (adolescents between 12 and 19 years old), followed by adults (20 to 64 years old) and elderly people (over 65 years old). Conclusion In summary, the EHL rFVIII offers the optimal prophylaxis by decreasing the dose frequency, increasing the treatment adherence and improving the QoL, without compromising safety and efficacy.
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Hémophilie A , Facteur VIII , Méthode DelphiRÉSUMÉ
ABSTRACT BACKGROUND: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results. OBJECTIVES: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis. DESIGN AND SETTING: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil. METHODS: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds. RESULTS: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: −1.58; 95% confidence interval −2.50, −0.66, P = 0.0008; I2 = 68.4%, P = 0.0031). CONCLUSION: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results. SYSTEMATIC REVIEW REGISTRATION: CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.
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Introducción: el desarrollo de inhibidores contra el factor VIII (FVIII) es la complicación más seria del tratamiento en la hemofilia A. La inducción de tolerancia inmune (ITI) permite utilizar nuevamente el concentrado de FVIII para profilaxis o tratamiento. Objetivos: describir la experiencia con la ITI en menores de 18 años con hemofilia A severa (HAS) en un prestador integral de salud pública. Material y métodos: estudio descriptivo, retrospectivo, de menores de 18 años con HAS, concentraciones de inhibidores de FVIII ≥ a 5 UB, a quienes se les realizó ITI y seguimiento completo entre 2009 y 2020. Para la ITI se utilizó concentrado de FVIII derivado plasmático. El beneficio se expresa como la tasa de éxito definido por la negativización del inhibidor. Resultados: se incluyeron seis pacientes. Edad promedio al diagnóstico de inhibidor 2,96 años, luego de 24,4 días de exposición (DDE) a concentrados de FVIII. Media de inicio de ITI 3,76 niños y el tiempo de latencia del diagnóstico de inhibidor y el inicio de la ITI fue de 10,33 meses. El pico máximo del título pre-ITI fue en promedio de 114,7 UB. Cuatro pacientes iniciaron el régimen de ITI con títulos de inhibidor menor a 10 UB. El título del inhibidor se negativizó en 8,2 meses y el porcentaje de recuperación in vivo >65% se logró con una media de 15,7 meses. La ITI fue exitosa en 83% de los casos. Conclusiones: en niños con hemofilia A e inhibidores de alto título, la ITI tiene un elevado éxito, tal como ocurrió en esta serie. Dado que el tiempo de respuesta es variable, la ITI debe ser individualizada.
Introduction: the development of inhibitors against factor VIII is the most serious complication of treatment in hemophilia A. Immune tolerance induction (ITI) enables the factor VIII concentrate to be used again for prophylaxis or treatment. Objectives: describe the experience with ITI in children of under 18 years of age with severe hemophilia A (SAH) in a health care provider. Material and methods: descriptive, retrospective study of children under 18 years of age with SAH, concentrations of FVIII inhibitors ≥ 5BU, who underwent ITI and full follow-up between 2009-2020. For ITI, we used plasma derived FVIII concentrate. The benefit is expressed as the success rate defined by the inhibitor's negativization. Results: 6 patients were included. Mean age at diagnosis of inhibitor 2,96 years, after 24,4 days of exposure (DAE) to FVIII concentrates. Mean ITI onset was 3,76 years and latency time from inhibitor diagnosis and ITI onset was 10,33 months. Maximum peak of the pre ITI title was an average of 114,7 UB. Four patients started the ITI regimen with inhibitors titers less than 10 BU. The inhibitor titer negative in 8,2 months and in vivo recovery rate >65% was achieved with a mean of 15,7 months. The ITI was successful in 83% of the cases. Conclusions: ITI is highly successful in children with hemophilia A and high-titer inhibitors, as this case suggests. Since the response time is variable, the ITI must be individualized.
Introdução: o desenvolvimento de inibidores contra o fator VIII é a complicação mais grave do tratamento da hemofilia A. A indução de tolerância imunológica (ITI) permite que o concentrado de fator VIII seja novamente utilizado para profilaxia ou tratamento. Objetivos: descrever a experiência com ITI em crianças menores de 18 anos com hemofilia A grave (HAS) em um serviço de saúde pública abrangente. Material e métodos: estudo descritivo e retrospectivo de crianças menores de 18 anos com HAS, concentrações de inibidor do FVIII ≥ 5 BU), que realizaram ITI e acompanhamento completo entre 2009-2020. Concentrado de FVIII derivado de plasma foi utilizado para ITI. O benefício é expresso como a taxa de sucesso definida pela negativação do inibidor. Resultados: 6 pacientes foram incluídos. Idade média no diagnóstico do inibidor 2,96 anos, após 24,4 dias de exposição (DDE) a concentrados de FVIII. A média de início da ITI foi de 3,76 crianças e o tempo de latência do diagnóstico do inibidor e início da ITI foi de 10,33 meses. O pico máximo do título pré-ITI foi em média 114,7 BU. Quatro pacientes iniciaram o regime ITI com títulos de inibidor inferiores a 10 BU. O título do inibidor tornou-se negativo em 8,2 meses e a percentagem de recuperação in vivo >65% foi alcançada com uma média de 15,7 meses. O ITI foi bem-sucedido em 83% dos casos. Conclusões: em crianças com hemofilia A e inibidores de títulos elevados, a ITI é altamente bem sucedida, como ocorreu nesta série. Como o tempo de resposta é variável, o ITI deve ser individualizado.
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Humains , Facteur VIII/antagonistes et inhibiteurs , Coagulants/antagonistes et inhibiteurs , Hémophilie A/traitement médicamenteux , Tolérance immunitaire/effets des médicaments et des substances chimiques , Facteur VIII/usage thérapeutique , Coagulants/usage thérapeutique , Maladie catastrophique , Études rétrospectives , Études de suiviRÉSUMÉ
La hemofilia adquirida es un trastorno hemostático causado por la presencia de autoanticuerpos inhibidores contra el F VIII de la coagulación. Clínicamente se presenta como sangrado espontáneo, principalmente en piel y tejidos blandos, y a diferencia de la hemofilia congénita, la hemartrosis es rara. Se presenta el caso de un paciente de sexo masculino, de 60 años, previamente sano, que acude a consulta por cuadro de 8 días de evolución de aparición de hematomas a nivel de miembro superior e inferior. Durante su evolución presenta TTPA alargado y concentraciones bajas de F VIII.
Acquired hemophilia is a hemostatic disorder caused by the presence of inhibitory autoantibodies against coagulation F VIII. Clinically it presents as spontaneous bleeding, mainly in the skin and soft tissues, and unlike congenital hemophilia, hemarthrosis is rare. We present the case of a 60-year-old male patient, previously healthy, who came to the clinic due to an 8-day history of hematomas on the upper and lower limbs. During its evolution it presents prolonged APTT and low concentrations of F VIII.
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A sinovectomia radioativa (SR) é considerada o tratamento de eleição no controle da sinovite crônica não responsiva ao tratamento conservador, sendo recomendado tratamento fisioterapêutico para a melhora da funcionalidade. Objetivo: Verificar a influência do tratamento fisioterapêutico na independência funcional e saúde articular de hemofílicos após tratamento com SR. Método: Trata-se de um estudo descritivo, retrospectivo, analítico e metodologia quali-quantitativa. Realizou-se avaliação fisioterapêutica, aplicação do HJHS para avaliação da saúde articular e Escore FISH para avaliação da independência funcional. Os participantes foram subdivididos em dois grupos de acordo com a realização ou não da fisioterapia após a SR. Resultados: Participaram do estudo 8 pessoas com hemofilia A, sexo masculino, média de idade de 19±5,3 anos. Foram 12 articulações submetidas a SR, dessas 41,67% cotovelos, 33,33% joelhos e 25% tornozelos. Na comparação dos grupos, não houve diferença estatística entre os eles nas variáveis: saúde articular e a Independência Funcional. Conclusão: O estudo é uma primeira tentativa de descrever o impacto da fisioterapia na independência funcional e saúde articular de hemofílicos submetidos à SR. Embora possua limitações, foi possível observar que o grupo que não realizou fisioterapia apresentava melhor saúde articular e melhor independência funcional previamente à SR em comparação ao grupo que realizou fisioterapia; porém, o grupo fisioterapia apresentava pior quadro global, com a funcionalidade impactada por outras articulações e não somente aquela tratada com SR, apresentando maior número de articulações alvo.
Radioactive synovectomy (RS) is considered the treatment of choice in the control of chronic synovitis resistant to conservative treatment, and physiotherapy is recommended to improve functionality after procedure. Objective: The aim was to verify the effects of physiotherapy on functional independence and joint health after RS. Method: This is a descriptive, retrospective, analytical study with qualitative/quantitative methodology. Physiotherapeutic evaluation, Hemophilia Joint Health Score (HJHS) application for joint outcome assessment and Functional Independence Score in Hemophilia (FISH) were used to measure the patient's functional ability. The participants were divided into two groups: one group underwent a physiotherapy program and one not treated with physiotherapy after RS. Results: The study included 8 people with hemophilia A, all male, their mean age was 19±5.3 years. Twelve joints were submitted to RS, in which 41.67% elbows, 33.33% knees and 25% ankles. In the comparison of the groups, there was no statistically significant difference between them in joint health and functional independence. Conclusion: The study is a first attempt to describe the impact of physiotherapy on functional independence and joint health of hemophilic patients submitted to SR. Although this study has limitations, it was possible to observe that the group not treated with physiotherapy had better joint health and better functional independence prior to SR compared to the group that underwent physiotherapy, but the group treated with physiotherapy had worse overall health and have their functionality impacted by joints other than those treated with RS, presenting a higher number of target joints.
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Resumen Introducción: El emicizumab (Hemlibra®, ROCHE) es un anticuerpo monoclonal IgG4 bi-específico, recombinante y humanizado, que mimetiza la función del FVIIIa. Su administración por vía subcutánea es eficaz y segura en la prevención de hemorragias en pacientes con hemofilia A severa con o sin inhibidor. Si bien el emicizumab ha sido aprobado con un régimen de administración basado en el peso corporal y sin un monitoreo de los niveles plasmáticos, la cuantificación plasmática de emicizumab puede ser útil en distintas circunstancias clínicas y de investigación. Debido a que en Argentina aún no están disponibles los calibradores y controles comerciales específicos de emicizumab, hemos validado un método para la cuantificación plasmática de emicizumab (Epc), basado en la medición de FVIII por método coagulométrico en una etapa modificado (modFVIIIcoag), utilizando calibradores y controles preparados "in-house". Materiales y métodos: para la Epc se utilizó una predilución de la muestra 1/80 con buffer Owren Koller. El calibrador "in-house" de emicizumab (150 μg/mL de emicizumab) se preparó agregando emicizumab de 150 mg/ml a un plasma deficiente en FVIII. Se prepararon dos niveles de control "in-house" y una curva de calibración de 6 puntos. Los procedimientos de validación se realizaron en un STA Compact Max2 (Diagnostica Stago). Repetibilidad: se procesaron los controles 20 veces en la misma corrida analítica. Imprecisión Intra-Laboratorio: se procesaron los controles por triplicado durante 5 días. Linealidad:11 niveles medidos por triplicado. Límite de cuantificación: 15 mediciones de un plasma deficiente de FVIII comercial. Bias: a partir de un programa de evaluación externa de calidad (UK NEQAS). Se evaluó la interferencia del FVIII y rFVIIa en Epc, y de emicizumab en otras determinaciones de hemostasia. Resultados: Epc mostró una imprecisión y un sesgo aceptables, un rango lineal de 5-150 µg/ml y un límite de cuantificación de 5 µg/ml de emicizumab. En los estudios de interferencia se encontró que el FVIII interfiere con Epc pero no así el rFVIIa. Emicizumab acortó los valores del TTPa por debajo del límite inferior del intervalo de referencia local, mientras que el FVIII medido por método cromogénico con componentes de origen bovino no fue afectado. El método coagulométrico de una etapa de FVIII fue falsamente aumentado y mostró una fuerte correlación lineal con Epc en este sistema reactivo/instrumento. Discusión: El ensayo modFVIIIcoag automatizado "in-house" permite la cuantificación plasmática de emicizumab mediante un método sencillo, reproducible, de bajo costo y de fácil integración en los procesos de rutina.
Abstract Introduction: Emicizumab (Hemlibra®, ROCHE) is a bispecific, recombinant and humanized IgG4 monoclonal antibody, that mimics the function of FVIIIa. Its subcutaneous administration is effective and safe in preventing bleeding in patients with severe hemophilia A with or without inhibitor. Although emicizumab has been approved with an administration regimen based on body weight and without monitoring of plasma levels, emicizumab plasma quantification may be useful in different clinical and research circumstances. Since emicizumab-specific commercial calibrators and controls are not yet available in Argentina, we have validated a modified one-stage FVIII assay (modOSA) for the quantification of emicizumab in plasma (Epq) using in-house prepared calibrators and controls. Materials and methods: For Epq a 1/80 sample predilution with Owren Koller buffer was used. In house emicizumab calibrator (150 μg/mL emicizumab) was prepared by adding emicizumab 150 mg/mL to FVIII deficient plasma. Two in house control levels and a 6-point calibration curve were prepared. The validation procedures were performed in a STA Compact Max2 analyser (Diagnostica Stago). Repeatability: controls were processed 20 times in the same analytical run. Intra-laboratory Imprecision:controls were processed in triplicate for 5 days. Linearity: 11 levels were measured in triplicate. Limit of quantitation: 15 measurements of a commercial FVIII deficient plasma were assessed. Bias were estimated based on an external quality assessment program (UK NEQAS). The interference of FVIII and rFVIIa in Epq and of emicizumab in other hemostasis determinations were evaluated. Results: Epq showed acceptable imprecision and bias, a linear range of 5-150 µg/ml and a quantification limit of 5 µg/ml. Epq was interfered with FVIII but not with rFVIIa. Emicizumab shortened aPTT values below the lower limit of the local reference interval. FVIII measured by chromogenic method with components of bovine origin was not affected. The one-stage FVIII assay (OSA) was falsely increased but showed a strong linear correlation with Epq in this instrument reagent system. Discussion: The automated "in-house" modOSA allows the plasma quantification of emicizumab using a simple, reproducible, low-cost method that is easy to integrate into routine processes.
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RESUMEN La hemofilia A adquirida es un trastorno hemorrágico poco frecuente a nivel mundial, y se caracteriza por la presencia de autoanticuerpos inhibidores dirigidos hacia un factor de la coagulación, en la mayoría de ocasiones el factor VIII. Las etiologías son variadas, entre las que se encuentra el posparto. Se presenta el caso de una paciente de 34 años con dolor lumbar, hematuria y hematoma en región glútea derecha, sin antecedentes previos de sangrado. Por extensión de las manifestaciones hemorrágicas es transferida al servicio de emergencia. Los exámenes auxiliares de perfil de coagulación, prueba de mezclas y medición de los títulos de inhibidores del factor VIII permitieron confirmar el diagnóstico. El caso resalta la importancia de considerar esta patología en una paciente puérpera con persistencia de sangrado por herida operatoria, hematoma extenso y sin historia de sangrado previo.
ABSTRACT Acquired hemophilia A is a rare bleeding disorder worldwide, characterized by the presence of inhibitory autoantibodies directed against a coagulation factor, most often factor VIII. There are several possible causes, and it can occur during the postpartum period. We present the case of a 34-year-old female patient with back pain, hematuria and a right gluteal hematoma, with no previous history of bleeding. She was transferred to the emergency department due to the extension of the hemorrhagic manifestations. Diagnosis was confirmed with the coagulation profile, mixing test and the assessment of factor VIII inhibitor tier. The case highlights the importance of considering this condition in a postpartum patient with persistent postoperative bleeding, extensive hematoma and no history of previous bleeding.
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Humains , Femelle , Grossesse , Service hospitalier d'urgencesRÉSUMÉ
Resumen La hemofilia es una diátesis hemorrágica producida por la deficiencia hereditaria de un factor (proteína) de la coagulación sanguínea que afecta principalmente a los varones. Su grado de severidad puede variar desde casos con poco sangrado, hasta condiciones muy graves que en muchas ocasiones llevan a la muerte a los enfermos. Existen dos tipos de hemofilia: la A por carencia del factor VIII y la B por falta del factor IX. En este editorial se resume de manera global la situación actual de los avances de la hemofilia desde el punto de vista clínico y del laboratorio.
Abstract Hemophilia is a hemorrhagic diathesis that is caused by the hereditary deficiency of a factor (protein) of blood clotting and that affects mainly men. Its degree of severity can vary from cases with little bleeding, to very serious conditions that often lead to death. There are two types of hemophilia, A for lack of factor VIII, and B for lack of factor IX. This editorial summarizes the current state of progress of hemophilia from the clinical and laboratory point of view.
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Humains , Hémophilie B/traitement médicamenteux , Hémophilie A/traitement médicamenteux , Troubles hémorragiquesRÉSUMÉ
Background: Hemophilia A (Factor VIII deficiency) is a X-linked coagulopathy that affects approximately 1/10,000 male live births. In the past, the treatment of hemophilia A consisted of cryoprecipitated plasma and purified factor preparations. As a result, they experienced unusually high incidence of hepatitis and human immunodeficiency virus (HIV) seroconversion. Aims and Objectives: The aims of this study were to find out the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infection, among hemophiliacs attending a tertiary care center in Kerala, southern India. Materials and Methods: A cross-sectional study was conducted on hemophilia A patients who attended the departments of medicine and paediatrics. Demographic details and treatment history were obtained by questionnaire. Enzyme-linked immunosorbent assay was used to detect HBV surface antigen, HCV antibodies, and HIV. The statistical data analysis was performed using SPSS software version. Results: Out of 90 hemophilia A patients who underwent testing for the seroprevalence of transfusion-transmitted viral infections, one (1.1%) patient tested positive for HIV, two (2.2%) for HCV, and one (1.1%) for HBV. Among patients with hemophilia A, the prevalence of transfusion-transmitted infection was 4.4%. Patients with HIV- and HCV-positive tests belonged to the severe hemophilia A group. Moreover, the HBV-positive patient belonged to moderate hemophilia A. Conclusion: The present paradigm of management of hemophilia A patients is with plasma-derived or recombinant Factor VIII concentrates, cryoprecipitates, and fresh frozen plasma. Due to the risk, however remote, of transfusion-transmitted viral infections, all hemophiliacs should receive the hepatitis B vaccine and undergo routine testing for HIV, HCV, and HBV viruses.
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Background: Deficiency of factor VIII (FVIII) (Hemophilia A) and factor IX (Hemophilia B) are the most frequent coagulation defects. The incidence of hemophilia A varies in different regions of India. Aims and Objectives: The present study was done to classify hemophilia A patients by estimating FVIII levels in them and to describe the clinical profile of the patients attending a tertiary care hospital in southern part of India, Kerala. Materials and Methods: A hospital-based cross-sectional study was done on patients with hemophilia A, attending Department of Medicine and Department of Pediatrics from March 2012 to September 2013. Demographic and clinical details were collected using per forma and quantitative assessment of FVIII levels were done using semi-automated blood coagulation analyzer. Results: Out of 90 cases studied, majority of the patients had severe hemophilia (85.6%), followed by mild (10%) and moderate hemophilia (4.4%). Positive family history was seen in 67.8% patients. Median age of the patients at diagnosis was 1 years of age. Most common clinical presentation was found to be hemarthrosis (84.4%) followed by bleeding into muscle (56.7%). Knee joint (75.6%) was the predominantly affected joint. Bony ankylosis (30%), intracranial bleed (14.4%), and retroperitoneal bleed (24.4%) were the most common complications noted. Bleeding manifestations such as gum bleed (24.4%), epistaxis (12.2%), hematuria (37.8%), and ecchymosis (15.6%) were also reported among them. Conclusion: Proportion of severe hemophilia among hemophilia A patients was found to be higher in number than in other parts of the country. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Therefore, promotion of low cost, regular availability of factor concentrates, prophylactic factor replacement, establishing comprehensive care center, and regular training of medical and paramedical staff will help in reducing the complications due to this disease.
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Presentamos el caso de un paciente varón de 24 años con hemofilia A de 14 años de evolución. El paciente presentó hemartrosis recurrente en rodilla derecha, luego desarrolló artritis séptica en dicha articulación producida por Serratia marcescens con respuesta satisfactoria al lavado intra-articular con solución salina y 28 días de tratamiento con carbapenémicos. En pacientes con artritis séptica, hemartrosis previa y múltiples ingresos hospitalarios debe sospecharse la presencia de este germen. El tratamiento es quirúrgico y con antibióticos de amplio espectro.
We present the case of a 24-year-old male patient with hemophilia A of 14 years of evolution. The patient presented recurrent hemarthrosis in the right knee, who developed septic arthritis in knee due to Serratia marcescens with a satisfactory response to intra-articular lavage with saline solution and 28 days of treatment whith carbapenems. In patients with septic arthritis, previous hemarthrosis and multiple hospital admissions, the presence of this germ should be suspected. The treatment is surgical and with broad spectrum antibiotics.
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【Objective】 To evaluate the efficacy and safety of plasma-derived human coagulation factor Ⅷ (FⅧ) in the treatment of patients with hemophilia A. 【Methods】 A multi-center and open, SAT(single-arm trials) clinical study was conducted. A total of 54 subjects with hemophilia A were enrolled in 5 research centers. FⅧ was injected according to the subjects' weight, severity of disease and other factors, and the transfusion efficiency of FⅧ activity at 10 min after the first infusion of the first bleeding event was taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs within 24 h after the first infusion of the first bleeding event were the secondary efficacy indexes. The pathogenic microbial indexes and FⅧ inhibitors were detected on 90(th) and 180(th) day after treatment. 【Results】 The transfusion efficiency of FⅧ activity of 54 subjects at 10 min after the first infusion was 171.9% on average, with median of 169.5%, both higher than the target value of 100%. Within 24 h after the first infusion, the improvement of bleeding symptoms and signs of the subjects were scored, among which 19 cases (35.2%) were "obvious", 35 cases (64.8%) were "good", and the total clinical effective rate reached 100%. Five subjects (9.3%) had six drug-related adverse events. On 90(th) and 180(th) day after treatment, hepatitis B surface antigen, hepatitis C antibody, HIV antibody, treponema pallidum antibody and FⅧ inhibitors were detected, and no negative to positive cases were found. 【Conclusion】 After infusion, the FⅧ preparation can significantly improve the FⅧ activity level in hemophilia A patients in a short period of time, which has high infusion efficiency and can achieve better treatment efficacy, and can also effectively control and relieve bleeding symptoms and signs, with good overall safety.
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Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.
Sujet(s)
Humains , Hémophilie A/traitement médicamenteux , Facteur VIII/usage thérapeutique , Qualité de vie , Études rétrospectives , Hémarthrose/prévention et contrôle , Hémorragie/traitement médicamenteuxRÉSUMÉ
Objective To evaluate the performance of myPKFiT,a tool guiding the dosing of antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM),in maintaining the coagulation factor Ⅷ (FⅧ) level above a target threshold at the steady state and estimating the pharmacokinetics (PK) parameters in hemophilia A patients in China. Methods The data of 9 patients with severe hemophilia A in a trial (CTR20140434) assessing the safety and efficacy of rAHF-PFM in the Chinese patients with hemophilia A were analyzed.The myPKFiT was used to predict the adequate dose to maintain a patient's FⅧ level above target threshold at the steady state.Furthermore,the performance of myPKFiT in estimating the pharmacokinetics parameters of individuals was evaluated. Results Twelve combinations of two dosing intervals and six sparse sampling schedules were investigated,and 57%-88% of the patients remained the FⅧ level above the target threshold of 1 U/dl (1%) for at least 80% of the dosing interval.The clearance and time to FⅧ level of 1% obtained from sparse sampling by myPKFiT were similar to those obtained from extensive sampling. Conclusions The myPKFiT can provide adequate dose estimates to maintain the FⅧ level above the target threshold at the steady state in Chinese patients with severe hemophilia A.Moreover,it demonstrates good performance for estimating key pharmacokinetics parameters,including clearance and time to FⅧ level of 1%.
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Humains , Chine , Peuples d'Asie de l'Est , Facteur VIII/pharmacocinétique , Hémophilie A/traitement médicamenteuxRÉSUMÉ
Renal replacement therapy and perioperative management have difficulties in hemophilia patients with end-stage renal disease. The paper summarized the diagnosis and treatment experience of six hemophilia patients complicated with end-stage renal disease from January 1, 2000 to March 31, 2023 in Peking Union Medical College Hospital. Among 6 patients treated with peritoneal dialysis, 3 were treated with hemodialysis or continuous venous-venous hemodialysis. Altogether 11 dialysis access procedures were conducted successfully, and no serious bleeding or thrombotic events. In further conjunction with literature review, the paper summarized the key points of dialysis access appliance relevant to such patients, to provide reference for renal replacement treatment paths.
RÉSUMÉ
OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31(16-50) years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.
Sujet(s)
Adulte , Humains , Adulte d'âge moyen , Adolescent , Jeune adulte , Facteurs de la coagulation sanguine , Facteur VIII/pharmacocinétique , Hémophilie A , Hémorragie , Protéines recombinantes/pharmacocinétiqueRÉSUMÉ
Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.
Sujet(s)
Humains , Hémophilie A/thérapie , Systèmes CRISPR-Cas , Hémophilie B/thérapie , Édition de gène , Thérapie génétique , Vecteurs génétiquesRÉSUMÉ
The history of hemophilia is ancient, with descriptions dated to the 2nd century AD. The first modern narratives appeared in 1800s, when total blood transfusion was the only available treatment and life expectancy was remarkably low. Advances occurred with the use of plasma and cryoprecipitate, but only the discovered of factor concentrates revolutionized the treatment. The implantation of prophylaxis allowed hemophilic patients to prevent bleeding and the development of chronic arthropathy, although with a significant burdensome with the regular infusions. In the past 20 years, this field has witnessed major improvements, including the development of gene therapy and other pharmacological approaches.