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.

Advances in AAV-CRISPR/Cas9-Mediated Hemophilia A Gene Therapy --Review / 中国实验血液学杂志

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.

Analysis of APTT Mixing Test Results in Factor Ⅷ Inhibitor-Positive Hemophilia Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the results of activated partial thromboplastin time (APTT) mixing test in coagulation factor Ⅷ inhibitor-positive hemophilia patients, so as to increase the value of APTT mixing test in the screen of factor Ⅷ inhibitor.@*METHODS@#Eighty plasmas samples with different titers of coagulation factor Ⅷ inhibitors had been collected and diluted for routine immediate APTT mixing test and at 37 ℃ 2 hours incubation APTT mixing test. Fifteen samples were selected for immediate and normal temperature incubation for 15 min, 30min, 1 hour, 2 hours and 37 ℃ for 30 min, 1 hour, 2 hours APTT mixing test.@*RESULTS@#The results of APTT mixing test were significantly correlated with the titers of coagulation factor Ⅷ inhibitors. The ROC curve result showed that the best diagnostic cut-off value for 2 hours incubation APTT mixing test at 37 ℃ to determine the presence or absence of coagulation factor Ⅷ inhibitors was 43.8 s (sensitivity and specificity was 85.90% and 100%, respectively), while the best diagnostic cut-off value for distinguishing high-titer and low-titer Ⅷ inhibitors was 52.4 s (sensitivity and specificity was 98.18% and 95.65%, respectively). The critical coagulation factor Ⅷ inhibitor titer that could not be corrected by immediate APTT was 5.14 BU/ml, while that could not be corrected by 37 ℃ 2 hours incubation APTT was 1.31 BU/ml. Paired samples t -test was performed on the APTT mixing test results at different times and temperatures, and the differences were statistically significant (P < 0.05).@*CONCLUSIONS@#The APTT mixing test can be used as a screening index for coagulation factor Ⅷ inhibitors. APTT mixing test result shows a significant time-temperature dependence with lower titers of coagulation factor Ⅷ inhibitor. Patients with hemophilia who cannot be corrected by immediate APTT mixing test should be alert to the possibility of high titer of coagulation factor Ⅷ.

Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

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.

A case of acute severe cryptogenic organic pneumonia with secondary hemophilia / 中南大学学报(医学版)

Cryptogenic organic pneumonia (COP) refers to organic pneumonia that has not been identified a clear cause by current medical methods. A small proportion of COP can exhibit severe and progressive characteristics, while severe COP can cause systemic inflammatory storms and can be secondary to hemophilia. This article reported a case of acute severe COP secondary to hemophilia. A 67-year-old male patient was admitted to the hospital due to cough, shortness of breath, and fever. At first, he was misdiagnosed as severe pneumonia, but failed to receive anti infection treatments. Sputum pathogenetic examination and Macrogene testing of alveolar lavage fluid were performed, and no etiology was found to explain the patient's condition. The condition was gradually worsened and hemophilia occurred to explain, suggesting that acute severe COP was relevant. After receiving hormone treatment, the condition gradually relieved and the absorption of lung lesions improved. Hemophilia secondary to COP is rare, and the specific mechanism needs further study.

Systemic lupus erythematosus with acquired hemophilia A: A case report and literature review / 中南大学学报(医学版)

Systemic lupus erythematosus (SLE) complicated with acquired hemophilia A (AHA) is a rare condition with frequently delayed diagnosis and a high mortality rate, so it is necessary to strengthen the understanding of this disease. In this study, the characteristics and treatment in 1 case of SLE complicated by AHA is reported and analyzed, and a literature review is conducted. The patient was a 29-year-old young female with a 10-year history of SLE, the main clinical manifestation was severe abdominal bleeding. Laboratory tests revealed that the activated partial thromboplastin time (APTT) was notably prolonged (118.20 s), and the coagulation factor VIII activity (FVIII꞉C) was extremely decreased (0.20%) with high-titer of factor VIII (FVIII) inhibitor (31.2 BU/mL). After treating with high-dose glucocorticoid, immunoglobulin, cyclophosphamide, rituximab, blood transfusion, and intravenous infusion of human coagulation FVIII, the coagulation function and coagulation FVIII꞉C were improved, and FVIII inhibitor was negative without serious adverse reactions. During the next 5-year follow-up, the patient's condition was stable and no bleeding occurred. In the case of coagulation dysfunction in SLE, especially with isolated APTT prolongation, AHA should be screened. When the therapeutic effects of glucocorticoid combined with immunosuppressants are not desirable, rituximab could be introduced.

Stable Expression of Coagulation Factors by RPS6 Promoter / 中国实验血液学杂志

OBJECTIVE@#To screen better promoters and provide more powerful tools for basic research and gene therapy of hemophilia.@*METHODS@#Bioinformatics methods were used to analyze the promoters expressing housekeeping genes with high abundance, so as to select potential candidate promoters. The GFP reporter gene vector was constructed, and the packaging efficiency of the novel promoter was investigated with EF1 α promoter as control, and the transcription and activities of the reporter gene were investigated too. The activity of the candidate promoter was investigated by loading F9 gene.@*RESULTS@#The most potential RPS6 promoter was obtained by screening. There was no difference in lentiviral packaging between EF1 α-LV and RPS6-LV, and their virus titer were consistent. In 293T cells, the transduction efficiency and mean fluorescence intensity of RPS6pro-LV and EF1 αpro-LV were proportional to the lentiviral dose. The transfection efficiency of both promoters in different types of cells was in the following order: 293T>HEL>MSC; Compared with EF1 αpro-LV, RPS6pro-LV could obtain a higher fluorescence intensity in MSC cells, and RPS6pro-LV was more stable in long-term cultured HEL cells infected with two lentiviruses respectively. The results of RT-qPCR, Western blot and FIX activity (FIX∶C) detection of K562 cell culture supernatant showed that FIX expression in the EF1 α-F9 and RPS6-F9 groups was higher than that in the unloaded control group, and there was no significant difference in FIX expression between the EF1 α-F9 and RPS6-F9 groups.@*CONCLUSION@#After screening and optimization, a promoter was obtained, which can be widely used for exogenous gene expression. The high stability and viability of the promoter were confirmed by long-term culture and active gene expression, which providing a powerful tool for basic research and clinical gene therapy of hemophilia.

Analysis of the effects of low/intermediate dose of coagulation factor Ⅷ on 30 adult patients with severe hemophilia A in a single center / 中华血液学杂志

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.

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%.

Long-term clinical outcomes following total knee arthroplasty in patients with hemophilic arthropathy: a single-surgeon cohort after a 10- to 17-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#Total knee arthroplasty (TKA) can reduce severe joint pain and improve functional disability in hemophilia. However, the long-term outcomes have rarely been reported in China. Therefore, this study aimed to evaluate the long-term outcomes and complications of TKA in Chinese patients with hemophilic arthropathy.@*METHODS@#We retrospectively reviewed patients with hemophilia who underwent TKA between 2003 and 2020, with at least 10 years of follow-up. The clinical results, patellar scores, patients' overall satisfaction ratings, and radiological findings were evaluated. Revision surgery for implants during the follow-up period was recorded.@*RESULTS@#Twenty-six patients with 36 TKAs were successfully followed up for an average of 12.4 years. Their Hospital for Special Surgery Knee Score improved from an average of 45.8 to 85.9. The average flexion contracture statistically significantly decreased from 18.1° to 4.2°. The range of motion (ROM) improved from 60.6° to 84.8°. All the patients accepted patelloplasty, and the patients' patellar score improved from 7.8 preoperatively to 24.9 at the last follow-up. There was no statistically significant difference in clinical outcomes between the unilateral and bilateral procedures, except for a better ROM at follow-up in the unilateral group. Mild and enduring anterior knee pain was reported in seven knees (19%). The annual bleeding event was 2.7 times/year at the last follow-up. A total of 25 patients with 35 TKAs were satisfied with the procedure (97%). Revision surgery was performed in seven knees, with 10- and 15-year prosthesis survival rates of 85.8% and 75.7%, respectively.@*CONCLUSIONS@#TKA is an effective procedure for patients with end-stage hemophilic arthropathy, which relieves pain, improves knee functions, decreases flexion contracture, and provides a high rate of satisfaction after more than ten years of follow-up.

Prophylaxis in hemophilia

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis ­ the regular administration of therapeutic products to maintain hemostasis and prevent bleeding ­ is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs.

Hemophilia: a biography on therapeutical approaches

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.

Avaliação do perfil clínico-terapêutico e da resposta à profilaxia dos portadores de hemofilia A e B em um centro de referência no Ceará / Evaluation of the clinical-therapeutic profile and the response to prophylaxis of patients with hemophilia A and B in a reference center in Ceará

Objetivo: Avaliar o perfil clínico-terapêutico e a resposta à profilaxia em pacientes hemofílicos A e B em um centro de referência no Ceará. Métodos: Estudo de coorte retrospectivo, com dados de 133 hemofílicos A e B, em profilaxia entre 2016 e 2021, por meio de prontuários médicos e sistema Web Coagulopatias. Resultados: Os pacientes todos do sexo masculino em sua maioria foram hemofílicos A (93,2%), na forma grave, residentes em Fortaleza, com maior prevalência do município de Guaiúba. A maioria fazia uso de Fator VIII recombinante e em profilaxia secundária, em relação ao comprometimento articular a maioria não apresentou relato de hemartroses (66,9%), articulação-alvo (87,9%) ou artropatia (54,9%), porém os hemofílicos em profilaxia terciária apresentaram um maior comprometimento articular em relação a profilaxia primária e secundária. Verificou-se uma correlação negativa entre o tempo de profilaxia e a dose de fator utilizada, demonstrando que quanto maior o tempo de profilaxia menor a dose do fator utilizada. Um total de 13 hemofílicos A grave desenvolveram inibidor de fator VIII realizando imunotolerância (ITI) com sucesso total em 84,6%. Por meio da curva ROC, foi verificado uma associação entre a necessidade de ITI e a dose de fator de coagulação, com acurácia de 67,7% de que o uso de doses maiores de fator predispõe ao desenvolvimento de inibidores. Conclusão: Os dados do estudo permitem inferir que quanto mais precoce o tratamento de profilaxia menor é comprometimento articular, dose do fator utilizada e menor predisposição de desenvolver inibidores dos fatores da coagulação.

Objective: to evaluate the clinical-therapeutic profile and response to prophylaxis in hemophiliac A and B patients at a referral center in Ceará. Methods: Retrospective cohort study, with data from 133 hemophiliacs A and B, undergoing prophylaxis between 2016 and 2021, using medical records and the Web Coagulopathies system. Results: Most of the patients were male patients with severe hemophilia A (93.2%), residing in Fortaleza, with a higher prevalence in the city of Guaiúba. Most made use of recombinant Factor VIII and in secondary prophylaxis, in relation to joint involvement, the majority did not report hemarthroses (66.9%), target joint (87.9%) or arthropathy (54.9%). however, hemophiliacs on tertiary prophylaxis showed greater joint impairment in relation to primary and secondary prophylaxis. There was a negative correlation between the prophylaxis time and the factor dose used, demonstrating that the longer the prophylaxis time, the lower the factor dose used. A total of 13 severe A hemophiliacs developed factor VIII inhibitor performing immunotolerance (ITI) with total success in 84.6%. Using the ROC curve, an association was verified between the need for ITI and the dose of coagulation factor, with an accuracy of 67.7% that the use of higher doses of factor predisposes to the development of inhibitors. Conclusion: The study data allow us to infer that the earlier the prophylaxis treatment, the less joint impairment, the dose of the factor used and the less predisposition to develop coagulation factor inhibitors.

Evaluación de profilaxis con factor VIII de origen plasmático en pacientes con hemofilia A severa / Evaluation of factor VIII prophylaxis of plasmatic origin in patients with severe hemophilia A / Avaliação da profilaxia do fator VIII de origem plasmática em pacientes com hemofilia A grave

Introducción: la hemofilia A severa (HAS) es una enfermedad hemorrágica hereditaria causada por un déficit de factor VIII (FVIII) menor al 1%. Se presenta principalmente con sangrados articulares, los cuales provocan una artropatía hemofílica que afecta su independencia funcional. El uso de la profilaxis terciaria con FVIII ofrece beneficios en adultos disminuyendo la tasa anual de sangrado (TAS) y mejorando la independencia funcional. Objetivo: determinar el porcentaje de pacientes que logran mantener un nivel de FVIII mayor al 1%, conocer si existe una mejora en la independencia funcional, así como una disminución en la TAS con el régimen profiláctico empleado. Métodos: estudio observacional, analítico. Se incluyó a los pacientes con HAS que se controlaron en el Hospital de Clínicas "Dr. Manuel Quintela" durante 2020 en profilaxis con FVIII durante 12 meses. Se obtuvieron tres muestras separadas en el tiempo para dosificación de FVIII y se evaluó la TAS y la independencia funcional en cada paciente. Resultados: se analizaron ocho pacientes, todos presentaron valores de FVIII superiores al 1% a la hora y 24 horas posterior a la administración de FVIII. Los episodios de sangrado se redujeron 4,76 veces con el uso de la profilaxis (p = 0,019). La independencia funcional mostró que 5/8 pacientes mejoraron al menos 1 punto del score. Conclusiones: la profilaxis terciaria en estos pacientes fue beneficioso en reducir la TAS y mejorar su capacidad funcional.

Summary: Introduction: severe hemophilia A (SAH) is an hereditary hemorrhagic disease, caused by a factor VIII (FVIII) deficiency of less than 1%. It presents with joint bleeding mainly, which causes a hemophilic arthropathy, which affects its functional independence. The use of tertiary prophylaxis with FVIII offers benefits in adults by decreasing the annual bleeding rate (ABR) and improving functional independence. Objective: to determine the percentage of patients who manage to maintain an FVIII level greater than 1%, to know if there is an improvement in functional independence, as well as a decrease in the ABR with the prophylactic regimen used. Methods: observational, analytical study. Patients with SAH who were controlled at the Hospital de Clínicas "Dr. Manuel Quintela", during the year 2020, in prophylaxis with FVIII for 12 months were included. Three samples separated in time for FVIII dosing were obtained and the ABR and functional independence were evaluated in each patient. Results: 8 patients were analyzed, all presented FVIII higher than 1% at one hour and 24 hours after the administration of FVIII. The bleeding episodes were reduced 4.76 times with the use of Prophylaxis (p = 0.019). Functional independence showed that 5/8 patients improved at least 1 point in the Score. Conclusions: tertiary prophylaxis in these patients was beneficial in reducing SAD and improving their functional capacity.

Introdução: a hemofilia A grave (HAS) é uma doença hemorrágica hereditária, causada pela deficiência do fator VIII (FVIII) inferior a 1%. Apresenta-se principalmente com sangramento articular, que causa artropatia hemofílica, que afeta sua independência funcional. O uso de profilaxia terciária com FVIII oferece benefícios em adultos, reduzindo a taxa de sangramento anual (TAS) e melhorando a independência funcional. Objetivos: determinar a porcentagem de pacientes que conseguem manter um nível de FVIII maior que 1%, identificar uma possível melhora da independência funcional, bem como uma diminuição da TAS com o esquema profilático utilizado. Métodos: estudo observacional, analítico de pacientes com HAS controlados no Hospital das Clínicas "Dr. Manuel Quintela", durante o ano de 2020, em profilaxia com FVIII durante 12 meses. Foram obtidas três amostras separadas no tempo para dosagem de FVIII e avaliação da TAS e da independência funcional de cada paciente. Resultados: foram analisados 8 pacientes, todos apresentaram FVIII maior que 1% em uma hora e 24 horas após a administração do FVIII. Os episódios de sangramento foram reduzidos 4,76 vezes com o uso da profilaxia (p = 0,019). A independência funcional mostrou que 5/8 pacientes melhoraram pelo menos 1 ponto do escore FISH. Conclusões: a profilaxia terciária nesses pacientes foi benéfica na redução da TAS e na melhora da capacidade funcional.

Analysis of epidemiological and economic data of hemophilia A patients in Brazil / Análise de dados epidemiológicos e econômicos de pacientes com hemofilia A no Brasil

Objective: To describe the annual medical direct costs per hemophilia A (HA) patient in the Brazilian public healthcare system (SUS) and to understand and describe the patients' hospital journey, demographical characteristics, and the procedures in the. Methods: This retrospective analysis of DataSUS databases. Data from individuals with registries of HA treatment were gathered between January 1st, 2018, and June 30th, 2021. Besides the D66 ICD-10th code (HA), were also considered the occurrence of some procedures like factor VIII dosage and by-pass therapy dispensation or administration as inclusion criteria. Exclusion criteria were occurrence of factor IX dispensation and female patients were excluded, among others. A record linkage using sociodemographic characteristics was conducted to identify unique patients. Results: Were identified 2,298 individuals underwent ambulatory and 1,018 underwent hospital treatments. The results show that most patients are from the Southeast region of the country, white and middle-aged individuals. The median cost of HA treatment per patient-year was BRL 90.36 for ambulatory care and BRL 1,015.31 for hospital care procedures. The costs were significantly higher for more severe patients and for those between 12 and 18 years old (BRL 1,974.75 and BRL 1,049.09, respectively). Conclusion: The evidence demonstrated encourages the implementation of policies aiming to improve the quality of care provided to patients with HA. Providing referral centers for hemophiliac patients is primordial for the success of the treatment and can result in efficiency.

Objetivo: Descrever os custos médicos diretos anuais por paciente com hemofilia A (HA) no sistema público de saúde brasileiro (SUS) e compreender e descrever a jornada do paciente em âmbito hospitalar, as características demográficas e os procedimentos realizados no SUS. Métodos: Análise retrospectiva das bases de dados do DataSUS. Foram coletados dados de indivíduos com registro de tratamento de HA entre 1º de janeiro de 2018 e 30 de junho de 2021. Além do código D66 CID-10 (HA), foi considerada a ocorrência de procedimentos como dosagem do fator VIII e dispensação ou administração de terapia de by-pass como critérios de inclusão. Dentre os critérios de exclusão, destacam-se a dispensação do fator IX e indivíduos do sexo feminino. Um pareamento de registros usando características sociodemográficas foi realizado para identificar pacientes únicos. Resultados: Foram identificados 2.298 indivíduos em tratamento ambulatorial e 1.018 em tratamento hospitalar. Os resultados mostraram que a maioria dos pacientes são da região Sudeste do país, brancos e de meia-idade. O custo médio do tratamento da HA por paciente-ano foi de R$ 90,36 para atendimento ambulatorial e de R$ 1.015,31 para atendimento hospitalar. Os custos foram significativamente maiores para pacientes mais graves e entre 12 e 18 anos (R$ 1.974,75 e R$ 1.049,09, respectivamente). Conclusão: As evidências demonstradas incentivam a implementação de políticas que visem melhorar a qualidade da assistência prestada aos pacientes com HA. A disponibilização de centros de referência para pacientes hemofílicos é primordial para o sucesso do tratamento e pode resultar em maior eficiência.

Therapeutic options for hemarthrosis in severe hemophilic patients / Opções terapêuticas para as hemartroses em pacientes hemofílicos graves

Introduction: Hemophilia A and B are rare congenital X-linked recessive diseases caused by lack or deficiency of the coagulation factors VIII (FVIII) or IX (FIX), respectively. The primary therapeutic approach is to replace the deficient coagulation factor, which can be achieved with factors derived from human plasma or recombinants. However, despite having a therapeutic approach, most severe cases are symptomatic and may have complications, mainly in the muscles and joints. One example of such disorder is hemarthrosis. This manifestation tends to affect mainly the knee, ankle, or elbow joints in about 80% of cases. Objective: to describe the primary forms of treatment for joint bleeding in patients with severe hemophilia. Methods: This is a qualitative research of the integrative review type meant to identify productions on topics associated with hemarthrosis and severe hemophilia. The articles were searched through the databases PubMed, Scientific Electronic Library Online (Scielo) and Virtual Health Library (BVS) with the following search descriptors: "hemarthrosis and hemophilia"; "joint diseases and Hemophilia" and corresponding terms in Portuguese. The inclusion criteria were as follows: a) scientific articles b) available in full-text c) studies available in Portuguese, English, or Spanish d) randomized clinical trials e) articles published between 2016 and 2021 f) articles containing hemarthrosis caused by severe hemophilia. As exclusion criteria, texts that had no relation to the theme, did not answer the guiding question, other types of articles that did not include randomized clinical trials and/or presented duplicates were discarded. Results: In total, 42 articles were found in the selected databases; eight were duplicated, and 25 were excluded for not being randomized clinical trials or because they did not contemplate the theme. After careful reading, nine articles that met the inclusion and exclusion criteria were identified. Of the eligible studies, one reported factor replacement, and eight reported physiotherapeutic treatment. Conclusion:Factor replacement for hemophilic patients is essential and, based on the information obtained, early replacement is ben-eficial for the patient to avoid joint complications. Prophylaxis is indicated in severe hemophilia and its main objective is to prevent recurrent hemarthrosis, which can cause permanent functional deformities. Some physiotherapeutic interventions are indicated to prevent joint damage in severe hemophilic patients. The findings show diversity in the physical therapy modalities employed. The complete prevention of joint damage is still a challenge. A combination of treatments and a multi-disciplinary team follow-up is necessary to ensure health and quality of life of patients. (AU)

Introdução: As hemofilias A e B são doenças congênitas raras, recessivas ligadas ao X, causadas por falta ou deficiência de fator de coagulação VIII (FVIII) ou IX (FIX), respectivamente. A terapêutica tem como conduta principal a reposição do fator de coagulação deficiente, podendo ser feita com fatores derivados de plasma humano ou recombinantes. Porém, apesar de possuir uma terapêutica, grande parte dos casos graves são sintomáticos e podem ter complicações, na sua maioria, nos músculos e nas articulações. Uma dessas desordens é a hemartrose. Essa manifestação tende a acometer principalmente articulações do joelho, tornozelo ou cotovelo em cerca de 80% dos casos. Objetivo: descrever as principais formas de tra-tamento para sangramento articular em pacientes com hemofilia grave. Método: Trata-se de uma pesquisa qualitativa do tipo revisão integrativa para identificação de produções sobre temas associados a hemartrose e hemofilia grave. A busca dos artigos foi através das bases de dados PubMed, Scientific Electronic Library Online (SciELO) e Biblioteca Virtual em Saúde (BVS) com os seguintes descritores de busca: "hemarthrosis and hemophilia"; "joint diseases and hemophilia" e termos correspondentes no português. Os critérios de inclusão foram os seguintes: a) artigos b) estar disponível em texto completo c) estudos disponíveis nos idiomas português, inglês ou espanhol d) ensaios clínicos randomizados e) artigos publicados entre 2016 e 2021 f) artigos que contemplem hemartrose por hemofilia grave. Resultados: No total, foram encontrados 42 artigos nas bases de dados selecionadas; oito estavam duplicados e 25 foram excluídos por não serem ensaios clínicos randomizados ou por não contemplarem a temática. Após leitura cuidadosa, foram identificados 9 artigos que atenderam aos critérios de inclusão e exclusão. Dos trabalhos elegíveis, um relatou sobre reposição de fator e oito artigos relataram sobre tratamento fisioterapêutico. Conclusão: A reposição de fatores para pacientes hemofílicos é essencial e, com base nas informações obtidas, a reposição precoce é benéfica para o paciente, evitando complicações articulares. A profilaxia está indicada na hemofilia grave e seu principal objetivo é prevenir a hemartrose recorrente, que pode causar deformidades funcionais permanentes. Algumas intervenções fisioterapêuticas são indicadas para prevenir danos articulares em pacientes hemofílicos graves. Os achados mostram diversidade nas modalidades de fisioterapia empregadas. A prevenção total dos danos articulares ainda é um desafio. É necessária uma combinação de tratamentos e acompanhamento por equipe multi-disciplinar de forma a garantir a saúde e qualidade de vida dos pacientes. (AU)

Impacto da hemofilia na qualidade de vida em relação à saúde de pacientes acompanhados pelo hemocentro de Alagoas / Impact of hemophilia on health-related quality of life of patients accompanied by the blood center of Alagoas

A qualidade de vida é um aspecto importante a ser considerado no plano terapêutico de qualquer paciente, principalmente aqueles que sofrem de doenças crônicas, como a hemofilia. Diante disso, esse estudo teve como objetivo avaliar a qualidade de vida em pacientes portadores de hemofilia atendidos pelo Hemocentro de Alagoas e descrever o perfil demográfico e socioeconômico. Foram 50 pacientes envolvidos na pesquisa, maiores de dezoito anos e portadores de hemofilia acolhidos pela associação e pelo hemocentro de Alagoas. A coleta de dados foi realizada por entrevistas utilizando-se de dois questionários: um sobre características demográficas e socioeconômicas e outro sobre avaliação da qualidade de vida relacionada à saúde (Haem-A-QoL). Desse total, 100% eram do sexo masculino, em que a maioria tinha idade entre 20 e 40 anos (80%), solteiro (62%), residentes no interior de Alagoas (58%), aposentado (56%), beneficiários da aposentadoria por complicação da hemofilia (60%), com renda pessoal no último mês de até um salário mínimo (78%) e sem plano de saúde privado (86%). A média do escore total do Haem-A-QoL foi 40,08 (variação de 0­96,46) com pior desempenho nos domínios "esporte e lazer" (média igual a 55,52) e "saúde física" (média igual a 50,16) e melhor nos campos de "relacionamentos e sexualidade" (média igual a 17,48). De modo geral, os hemofílicos do centro estudado apresentaram boa QVRS. A versão brasileira do Haem-A-QoL, demostrou ser um instrumento confiável, com boa consistência interna, revelando alguns problemas enfrentados pelos hemofílicos e que impactam na QVRS (AU)

Quality of life is a critical aspect in the therapeutic plan of any patient, especially those who suffer from chronic diseases, such as hemophilia. Thus, this study aimed to assess the quality of life in patients with hemophilia treated by the Blood Center of Alagoas and describe the demographic and socioeconomic profile. 50 individuals were enrolled in the study, being over 18 years old and with hemophilia treated by the Association and the Blood Center of Alagoas. Data collection was carried out through interviews using two questionnaires: one on demographic and socioeconomic characteristics, and the other on health-related quality of life (Haem-A-QoL). Of this total, 100% were male, most aged between 20 and 40 years (80%), single (62%), living in the interior of Alagoas (58%), retired (56%), beneficiaries of retirement due to hemophilia complications (60%), with personal income in the last month of up to one minimum wage (78%) and without a private health plan (86%). The mean of the total Haem-A-QoL score was 40.08 (ranging from 0-96.46), with the worst performance in the domains "sports and leisure" (mean of 55.52) and "physical health" (mean of 50.16), and the best performance in the domain "partnership and sexuality" (mean of 17.48). In general, the hemophiliacs in the center studied reported good health-related quality of life. The Brazilian version of Haem-A-QoL proved to be a reliable instrument, with good internal consistency, revealing some problems faced by hemophiliacs that impact on HRQoL

Calidad de vida relacionada con la salud de personas con hemofilia en el noreste de Brasil / Quality of life related to the health of people with hemophilia in Northeast Brazil

Introducción: La hemofilia se caracteriza por la ocurrencia de hemorragias frecuentes y afecciones del aparato locomotor graves en los pacientes que causan daños físicos, sociales y psicológicos y afecta directamente su calidad de vida relacionada con la salud. Objetivo: Evaluar la calidad de vida de personas con hemofilia en el noreste de Brasil. Métodos: Estudio epidemiológico transversal cuantitativo realizado con 13 personas con hemofilia de un Banco de Sangre en el noreste de Brasil. La recolección de datos se realizó mediante la aplicación de un cuestionario sociodemográfico y clínico y de Haem-A-Qol, utilizado para evaluar la calidad de vida de las personas con hemofilia. Los valores brutos y medios se calcularon en general para todos los dominios y luego para cada dominio para que pudieran mostrarse. Resultados: Se obtuvo un promedio total de 30,94 en relación a los diez dominios evaluados. Los dominios con los promedios más altos fueron "salud física" con 49,23 y "afrontamiento" con 35,89 y con el promedio más bajo fue "planificación familiar". Conclusiones: Los participantes de la investigación tienen una calidad de vida insatisfactoria en relación con la salud física y el afrontamiento y, satisfactoria en relación con las relaciones y la sexualidad(AU)

Introduction: Hemophilia is characterized by the occurrence of frequent bleeding and serious musculoskeletal conditions in patients that cause physical, social and psychological damage and directly affect their health-related quality of life. Objective: To evaluate the quality of life of people with hemophilia in the northeast of Brazil. Methods: Quantitative cross-sectional epidemiological study conducted with 13 people with hemophilia from a Blood Bank in northeastern Brazil. Data collection was performed by applying a sociodemographic and clinical questionnaire and Haem-A-Qol, used to assess the quality of life of people with hemophilia. Raw and mean values were calculated overall for all domains and then for each domain so that they could be displayed. Results: A total average of 30,94 was obtained in relation to the ten domains evaluated. The domains with the highest averages were "physical health" with 49,23 and "coping" with 35,89 and with the lowest average was "family planning". Conclusions: The research participants have an unsatisfactory quality of life in relation to physical health and coping, and satisfactory in relation to relationships and sexuality(AU)