Sangrado uterino anormal como presentación inicial de malignidades hematológicas / Abnormal uterine bleeding as the initial presentation of hematologic malignancies

El sangrado uterino anormal tiene una etiología variable, que va desde causas estructurales hasta causas funcionales, que se describen clásicamente en el acrónimo PALM-COEIN. No obstante, hay una pobre sensibilización de este síntoma como un marcador de enfermedades graves. En esta revisión se describe la relación de la hemorragia uterina anormal como síntoma clave o de presentación de malignidad hematológica, así como la posible relación con la hemofilia adquirida secundaria a neoplasia hematológica como causal del evento hemostático. Se realizó búsqueda en la literatura, con la mayoría de los artículos obtenidos de Medline, 24 de los cuales cumplieron con los objetivos para resolver la pregunta de investigación. Se encontraron diferentes malignidades hematológicas asociadas a sangrado uterino anormal, de las cuales la hemofilia adquirida y la trombocitopenia como potenciales causales de esta; la mayor correlación fue con leucemia, seguido de linfomas, y en menor cuantía la asociación con mieloma múltiple.

Abnormal uterine bleeding has a variable etiology, ranging from structural to functional causes, classically described by the acronym PALM-COEIN. However, there is poor awareness of this symptom as a marker of serious disease; in this review, we describe the relationship of abnormal uterine bleeding as a key symptom or debut of hematologic malignancy, as well as its possible relationship to acquired hemophilia secondary to hematologic neoplasia as causative of the hemostatic event. A literature search was performed, with most of the articles obtained from Medline, 24 of which met the objectives to solve the research question. Different hematological malignancies associated with abnormal uterine bleeding were found, of which acquired hemophilia and thrombocytopenia were found as potential causes; the highest correlation was with leukemia, followed by lymphomas, and to a lesser extent the association with multiple myeloma.

Planejamento e execução cirúrgica em paciente hemofílico fator XIII - relato de Caso / Surgical planning and execution in hemophiliac patient factor XIII ­ case report

A hemofilia por deficiência do fator XIII é uma doença que possui inúmeros riscos em cirurgia ou procedimentos invasivos, sendo o maior deles, a hemorragia. Na odontologia, para o profissional realizar procedimentos cirúrgicos em pacientes hemofílicos precisa estar capacitado com conhecimento teórico-prático de como realizar o pré, trans e pós-operatório, a fim de amenizar possíveis riscos e trazer segurança para o paciente e para ele. O presente estudo visa relatar uma exodontia em um paciente portador de hemofilia com deficiência do fator XIII, na Clínica Escola de Odontologia do Instituto Esperança de Ensino Superior (IESPES), objetivando trazer informações relacionadas à essa disfunção sanguínea e a conduta do cirurgião-dentista para um bom manejo odontológico neste grupo de pacientes.

Factor XIII hemophilia is a disease that poses several risks in surgery or invasive procedures, the greatest of which is hemorrhage. In dentistry, for the professional to perform surgical procedures in hemophilia patients need to be trained with theoretical and practical knowledge of how to perform the pre, trans and postoperative, in order to mitigate possible risks and bring safety for the patient and for him. The present study aims to report an exodontia in a patient with hemophilia with factor XIII deficiency in the Clínica Escola de Odontologia do Instituto Esperança de Ensino Superior (IESPES), aiming to bring information related to this blood dysfunction and the dental surgeon's conduct for a good dental management in patients affected by this pathology.

Extended half-life recombinant factor VIII treatment of hemophilia A in Brazil: an expert consensus statement

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.

Practice Exploration of the Two-way Referral under the Three-tiered System of Diagnosis and Treatment for Children with Hemophilia / 中国医院管理

Beijing Children's Hospital affiliated to the Capital Medical University set up a three-tiered system for hemophilia and explore solutions for local and remote referral modes.Through the establishment of electronic database,improving drug management,assisting medical insurance reimbursement and other auxiliary measures,it smooths the two-way referral path of children with hemophilia.It can rationally allocate medical resources,promote the development of local professional medical ability,make rational use of rare disease drugs,improve the efficiency of medical insurance funds,strengthen the service capability of children with rare diseases through the joint reform of three medical systems,and ensure the treatment of difficult and severe child patients,improve the accessibility of high-quality diagnosis and treatment,effectively reduce the financial burden of patients.

Inducción de tolerancia inmune en menores de 18 años con hemofilia A: experiencia en Uruguay, 2009-2020 / Induction of immune tolerance in children of under 18 years of age with hemophilia A: experience in uruguay, 2009-2020 / Indução de tolerância imune em crianças menores de 18 anos com hemofilia A: experiência no uruguai, 2009-2020

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.

Emicizumab prophylaxis in people with hemophilia A and inhibitors: a systematic review and meta-analysis

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.

Hemofilia adquirida tipo A

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.

Influência do tratamento fisioterapêutico na independência funcional de pessoas com hemofilia submetidas à sinovectomia radioativa / Influence of physiotherapeutic treatment on the functional independence of people with hemophilia submitted to radioactive sinovectomy

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.

Manejo odontológico de pacientes com hemofilia: revisão de literatura narrativa / Dental management of patients with hemophilia: narrative literature review

Objetivo: Apresentar aos profissionais de Odontologia, através de uma revisão de literatura narrativa, o manejo odontológico dos pacientes com hemofilia. Materiais e métodos: Foi realizada uma busca por artigos científicos em português e inglês, publicados nas bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (Pubmed) e ScienceDirect, datado entre os anos de 2007 a 2023. Para a busca, foram utilizados os descritores contidos na lista dos Descritores em Ciência da Saúde (DeCS), no idioma português: Transtornos da Coagulação Sanguínea, Transtornos Herdados da Coagulação Sanguínea e Hemofilia; e no idioma inglês: Blood Coagulation Disorders, Inherited Blood Coagulation Disorders e Hemophilia. Resultados: Nessa revisão, apresentamos o manejo odontológico dos pacientes hemofílicos, bem como as condutas adequadas nos principais procedimentos em que esses pacientes são submetidos. Conclusão: Os pacientes hemofílicos podem ser submetidos a qualquer procedimento odontológico, desde que o profissional tenha conhecimento necessário sobre a patologia e as condutas a serem tomadas. Para maior segurança e conforto do paciente e da equipe profissional, o tratamento deve ser bem-planejado pelo cirurgião-dentista e com apoio do médico hematologista.

Objective: To present to dental professionals, through a narrative literature review, the dental management of patients with hemophilia. Materials and methods: A search was carried out for scientific articles in Portuguese and English, published in the Scientific Electronic Library Online (SciELO), US National Library of Medicine (Pubmed) and ScienceDirect databases, dated between 2007 and 2023. the search used the descriptors contained in the list of Health Science Descriptors (DeCS), in Portuguese: Blood Coagulation Disorders, Inherited Blood Coagulation Disorders and Hemophilia; and in the English language: Blood Coagulation Disorders, Inherited Blood Coagulation Disorders and Hemophilia. Results: In this review, we present the dental management of hemophiliac patients, as well as the appropriate conducts in the main procedures in which these patients are submitted. Conclusion: Hemophiliac patients can undergo any dental procedure, as long as the professional has the necessary knowledge about the pathology and the actions to be taken. For greater safety and comfort of the patient and the professional team, the treatment must be well-planned by the dentist and with the support of the hematologist.

Clinical outcome and incidence of inhibitor development in severe hemophilia patients receiving low-dose prophylaxis: a 3-year follow-up study in Senegal, West Africa

ABSTRACT Introduction: In Africa, where access to diagnosis and treatment of hemophilia is the lowest in the world, prophylaxis is rarely used in preference to on-demand treatment. There are limited data of prophylaxis treatment from sub-Saharan Africa. The aim of this study was to evaluate clinical outcomes and inhibitor development in people with hemophilia receiving low-dose prophylaxis (LDP) in a sub-Saharan African setting. Methods: We conducted a three-year prospective study. A once or twice weekly prophylaxis regimen of 25 IU/kg of rFVIIIFc or 30 IU/kg of rFIXFc was given to Hemophilia A and B, respectively. We evaluated clinical outcomes and inhibitors occurrence, determined by screening and titration using the Nijmegen technique. Results: A total of 15 patients were included in the LDP regimen. The mean age was 6.3 years (1.5 - 10). A significant reduction was noted in the annualized bleeding rate, from 7.53 to 1.33 (p = 0.0001); the annualized joint bleeding rate passed from 3.6 to 1.4 (p = 0.001) and the proportion of severe bleeding, from 86.1% to 16.7% (p = 0.0001). The Hemophilia Joint Health Score (HJHS) moved from 9.6 to 3.4 (p = 0.0001) and the Functional Independence Score in Hemophilia (FISH) improved from 25.8 to 30.9 (p = 0.0001). School absenteeism decreased from 7.33% to 2.59%. Adherence to prophylaxis was 89.5% versus 60%. Consumption was 580 IU/kg/year versus 1254.6 IU/kg/year before and after prophylaxis, respectively. Incidence of inhibitors was 23% (3 /13 HA). Conclusion: The LDP in Hemophilia improves the clinical outcome without a surplus risk of inhibitor development. Using extended half-life clotting factor concentrates (CFCs) is better for prophylaxis in resource-limited countries, as they allow better compliance in treatment.

Hemofilia A adquirida en el posparto: reporte de caso / Postpartum-acquired hemophilia A: case report

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.

Nuevos paradigmas en la hemofilia / New paradigms in hemophilia

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.

Seroprevalence of hepatitis B, hepatitis C, and human immunodeficiency virus in hemophilia A patients: A descriptive study

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.

Clinical profile of Hemophilia A patients in a tertiary care hospital in Kerala, India: A cross-sectional study

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.

Artritis séptica de rodilla por Serratia marcescens en paciente con hemofilia A

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.

Prediction of Coagulation Factor Ⅷ Level in Chinese Hemophilia A Patients by the Pharmacokinetic Management Tool myPKFiT / 中国医学科学院学报

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%.

A Survey of the Current Status of Surgical Treatment of Hemophilic Osteoarthropathy in China Mainland 17 Grade A General Hospitals / 罕见病研究

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Dialysis and dialysis access issues in hemophilia patients with end-stage renal disease: a report of 6 cases and literature review / 中华肾脏病杂志

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.

Systematic review and meta-analysis of health state utility for global patients with hemophilia / 中国药房

OBJECTIVE To systematically sort out and evaluate the health state utility of hemophiliac patients， and to provide reliable parameters for conducting pharmacoeconomic evaluation and health technology assessment. METHODS Retrieved from CNKI， Wanfang data， VIP， CBM， PubMed， Embase， the Cochrane Library， Scopus and Web of Science databases， relevant literature about the measurement of health state utility in hemophiliac patients was collected from the inception to February 2023. After screening literature， extracting data and evaluating the quality of literature， meta-analysis was performed for health state utility with Stata 15.1 software. RESULTS Thirty-eight papers were finally included， with the highest and lowest health utility values of 0.90 and 0.46， respectively. Those studies mostly adopted the EuroQol Five Dimensions Questionnaire （EQ-5D） （73.7%）. Results of meta-analysis showed that health state utility of global hemophiliac patients was 0.69，95% confidence interval was 0.65- 0.74； those of patients with mild， moderate and severe hemophilia were 0.79， 0.70， and 0.64， respectively； health state utility for patients with inhibitors （0.64） was lower than that of patients without inhibitors （0.69）； health state utility for the Chinese patient population was 0.55， which was higher than that of Iranian patients （0.46）， but lower than those of other developed countries. CONCLUSIONS There is some heterogeneity in the results of the studies across countries/regions， with higher health state utility in developed countries than in developing countries. As the severity of hemophilia increases， the trend of decreasing health state utility is obvious.