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.

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.

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.

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.

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.

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%.

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.

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.

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.

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.

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.

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.

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.

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.