Electrocardiographic Findings Among Asymptomatic Adults With Haemophilia

Abstract Background: People with haemophilia (PwH) are living longer. Therefore, they can develop atherosclerotic cardiovascular disease (ASCVD). Electrocardiogram (ECG) alterations may be a sign of initial ASCVD before the occurrence of symptoms. Objective: To describe the prevalence of resting ECG alterations among PwH adults asymptomatic for ASCVD. Methods: PwH aged ≥ 30 years without previous ASCVD events were considered for the analysis. Resting ECG traces were analysed according to international reference values and the Brazilian Longitudinal Adult Health Study (ELSA-Brasil) results for asymptomatic Brazilian men. Based on the established normal values and using the QT index, we further described the altered ECGs as minor or major changes, according to the Minnesota Code. Differences between prevalences were evaluated by Pearson's χ2 test. Differences between medians were evaluated by the Mann-Whitney U test. A p-value < 0.05 was accepted as statistically significant. Results: A total of 64 PwH were included in the study. Median age was 44 years (interquartile range 35-52). Most patients had haemophilia A (81%) and 47% were severe. The prevalence of obesity, systemic arterial hypertension (SAH), diabetes mellitus (DM), and dyslipidaemia were 16%, 56%, 14%, and 72%, respectively. All the PwH had sinus rhythm, except for one, who had an implanted pacemaker due to idiopathic third-degree atrioventricular block. Altered ECGs were found in 25% and 30% of PwH, according to established criteria and ELSA-Brasil criteria, respectively. Major changes were found in eight (13%) PwH according to the Minnesota Code, including two ECGs with ischaemia-like wall inactivity. Conclusions: The prevalence of altered ECG varied from 25% to 30% among asymptomatic PwH.

Genetic analysis of a female child family with suspected X-linked recessive genetic disease / 中国热带医学

@#Objective　Genetic analysis was performed on a female child with chromosome Xq28 heterozygous deletion and suspected X-linked recessive disease to determine the morbidity and prognosis. Methods　A female child was admitted to the hospital on day 20 because of "jaundice for 20 days and difficulty in stopping bleeding at acupuncture sites". Low depth whole genome test of amniocentesis in late pregnancy suggested missing copy number of hemophilia A and X-linked mental retardation type 72. In order to further confirm the diagnosis and prognosis, peripheral blood of the children and their parents were collected for gene testing, chromosome inactivation test and genetic analysis. Results　Chromosome Xq28 of the child had 439.4 kb copy number heterozygous deletion variation, which was a clear disease-coding gene for functional loss included in ClinGen database. Chromosome inactivation test showed that the paternal X chromosome of the child was extremely inactivated. Haplotype analysis suggested that the normal chromosome of the subject was inherited from the mother, and there was heterozygous deletion on the paternal X chromosome, so it was inferred that the child will not develop disease or just have mild symptoms. Conclusion　It is necessary to analyze the X chromosome inactivation test for female patients with the pathogenic variation of X-linked recessive genetic disease to determine the possibility of the disease.

Haemophilia management programme: Transformation during COVID-19

Background & objectives: Haemophilia is a debilitating bleeding disorder with significant comorbidities affecting the quality of life. In India, the management of these individuals is still limited to on-demand institutional treatment with coagulant factors. In this study, we highlighted the problems faced by these patients in the COVID-19 period due to nationwide lockdown. Methods: A retrospective study was done to ascertain the trend in the number of patients with haemophilia A and B visiting the hospital, those succumbing to haemophilic complications and indications for factor requirement in the pre-COVID (October 2019-March 2020) and during the COVID-19 period (April-September 2020). Representative cases with unusual complications were described along with significant challenges faced in providing standard care of treatment to these individuals due to the COVID-19 pandemic. Results: A total of 818 and 162 individuals with haemophilia A and B, respectively, were registered with the department. The overall number of patient visits to the hospital significantly reduced from an average of 6.9 outpatient department (OPD) visits per patient in the pre-COVID-19 period to an average of 3.9 OPD visits per patient and admissions reduced to 50 per cent during the COVID-19 period. This led to a reduction in utilization of factors VIII and IX except VIIa for haemophilia with inhibitors. There was no factor utilization for elective surgeries during the COVID-19 period. A total of eight patients succumbed to haemophilia-related complications during the COVID-19 period due to delay in reaching the hospital. The challenges faced in the management of three cases with musculoskeletal bleeds, one case with scrotal haematoma and one with haemothorax during the COVID-19 period were also highlighted. Interpretation & conclusions: COVID-19 pandemic has unveiled the need for on-demand home treatment with coagulant factors and has also brought to light the existing need for primary prophylaxis, especially for younger individuals with haemophilia.

Comparación de la evaluación clínica y por ultrasonido de la artropatía hemofílica en pacientes pediátricos / Comparison of the clinical and ultrasound evaluation of haemophilic arthropathy in children

Resumen Antecedentes: La exploración articular por ultrasonido mediante el método HEAD-US en la detección de la artropatía temprana ha sido poco estudiada en nuestro país. Objetivo: Comparar la evaluación clínica y por ultrasonido de las articulaciones en niños con hemofilia. Métodos: Estudio longitudinal, prospectivo y descriptivo con pacientes pediátricos con hemofilia A y B valorados con la escala HJHS 2.1 y ultrasonido con transductor lineal de 8 a 12 MHz. Se evaluaron las articulaciones de codos, rodillas y tobillos de forma bilateral, con el método HEAD-US. Resultados: Se incluyeron 69 pacientes; de ellos, 48 con hemofilia A grave (peso: 40.1 kg). En la escala HJHS se observó mayor afectación en la rodilla izquierda (0.49) y menor en el tobillo derecho (0.05). Con la escala HEAD-US, la más afectada fue la rodilla derecha (0.78). Existe una relación significativa en la afectación de la rodilla derecha evaluada con la escala HEAD-US en presencia de inhibidor. Conclusiones: El peso superior al percentil 50 es un factor de riesgo independiente de complicaciones por sangrado articular, mientras que la edad y el tipo de hemofilia no parecen relacionados. El método HEAD-US es una herramienta útil y accesible para la detección temprana de artropatía y hemartrosis.

Abstract Background: Joint ultrasound examination using the HEAD-US method in the detection of early arthropathy is poorly studied in our country. Objective: To compare the clinical and ultrasound evaluation of the joints in haemophilia. Methods: Longitudinal, prospective and descriptive study with paediatric patients with haemophilia A and B evaluated with the HJHS 2.1 scale and ultrasound with a linear transducer of 8 to 12 MHz. Elbows, knees and ankles joints were evaluated bilaterally, with HEAD-US protocol. Results: 69 paediatric patients were included of which 48 with severe haemophilia A (weight: 40.1 kg). On the HJHS scale, a greater involvement was observed in the left knee (0.49), and less in the right ankle (0.05). With the HEAD-US scale, the most affected was the right knee (0.78). There is a significant relationship in the involvement of the right knee evaluated with the HEAD-US scale in the presence of inhibitor. Conclusions: Weight above the 50th percentile is an independent risk factor for joint bleeding complications, while age and type of haemophilia do not appear to be related. The HEAD-US method is a useful and accessible tool for early detection of arthropathy and hemarthrosis.

The minimum clinically-important difference in rehabilitation for children with haemophilic knee joint contracture / 中华物理医学与康复杂志

Objective:To determine the minimum clinically-important difference (MCID) in the rehabilitation effect among children with haemophilic knee joint contracture.Methods:The data describing 28 children with an average age of 13.89±3.00 years and haemophilic knee joint contracture who received no less than 10 sessions of physiotherapy in the Department of Rehabilitation Medicine at the Peking Union Medical College Hospital were analyzed. The therapeutic effect of the treatement was quantified in terms of Haemophilia Joint Health Scores (HJHSs) for their knees. The MCID after the therapy was evaluated using the mean change method, multivariate linear regression, receiver operating characteristics, and the distribution-based method.Results:The MCID for the improvement of knee HJHS was 5.13 by the mean change method, 4.31 by multivariate linear regression, 3.50 according to the ROC curve and 1.64 by the distribution-based method. Taking all of them into consideration, 4.31 was found to be an appropriate value.Conclusions:The MCID after physical therapy for the improvement in knee HJHS for a child with haemophilic knee contracture is 4.31. Improvements greater than 4.31 can be considered clinically significant.

Causes of death and mortality trends related to hemophilia in Brazil, 1999 to 2016

ABSTRACT Introduction Multiple cause of death methodology enhances mortality studies beyond the traditional underlying cause of death approach. Aim: This study aims to describe causes of death and mortality issues related to haemophilia with the use of multiple-cause-of-death methodology. Methods: Annual male haemophilia mortality data was extracted from the public multiple-cause-of-death databases of the Mortality Information System, searching deaths included in rubrics D66 "hereditary factor VIII deficiency" (haemophilia A), and D67 "hereditary factor IX deficiency" (Haemophilia B) of the International Classification of Diseases, Tenth Revision, and processed by the Multiple Cause Tabulator. Results: In Brazil, from 1999 to 2016, a total of 927 male deaths related to haemophilia occurred during the 18 year period, of which 418 (45,1 %) as underlying cause, and 509 (54,9 %) as associated cause of death. The leading associated cause of 418 deaths of haemophilia as underlying cause was hemorrhage (52.6%), half of which intracranial hemorrhage. Infectious and parasitic diseases accounted for 40,5% as the underlying causes of 509 deaths where haemophilia was an associated cause, where human immunodeficiency virus disease prevailed, however falling from 37,0% to 19.7%, and viral hepatitis increased from 6.0% to 7.9%; diseases of the circulatory system, increased from 13.5% to 18.4%, including intracranial hemorrhage from 5.7% to 7.0%, and neoplasms, from 8,5% to 13.2%, respectively from 1999-2007 to 2008-2016, followed as main underlying causes. Conclusion: Hemorrhages, mainly intracranial hemorrhage, human immunodeficiency virus disease, and viral hepatitis are the chief prevention goals aiming at the control of haemophilia mortality.

Rehabilitación física en pacientes con artropatía hemofílica: revisión sistemática y metaanálisis sobre dolor / Physical rehabilitation in haemophilic arthropathy: systematic review and pain-related meta-analysis

RESUMEN Introducción: La artropatía hemofílica (AH) cursa con diferentes manifestaciones clínicas importantes, como son las hemorragias articulares, el dolor, la disminución de la amplitud del movimiento y las alteraciones funcionales que pueden causar secuelas en la funciona lidad y movilidad. El ejercicio físico adaptado a los pacientes con hemofilia puede ser una adecuada estrategia terapéutica, que repercuta positivamente sobre la calidad de vida de dichos sujetos. Objetivos: Evaluar la eficacia de la rehabilitación física en el tratamiento de la artropatía hemofílica. Materiales y métodos: Se ha realizado una revisión sistemática y metaánálisis de ensayos clí nicos (seleccionados según criterios de elegibilidad). Para ello, se han utilizado las siguientes bases de datos: PEDro, Pubmed, Scopus y Web of Science. Se empleó la escala «PEDro¼ para evaluar la calidad metodológica de los estudios. Resultados: Tras aplicar los criterios de inclusión y exclusión, en la revisión final fueron incluidos siete artículos, los cuales aportaron resultados favorables sobre la fuerza y el diá metro muscular, el rango de movilidad, el estado articular y la calidad de vida. De ellos, dos estudios aportaron datos para metaanálisis, con resultados favorables sobre la variable dolor [Diferencia de medias estandarizada (DME) = -2,64; IC 95%: (-4,26; 1,03)]. Conclusiones: Se encontró evidencia sobre la eficacia de la rehabilitación física en el trata miento de la artropatía hemofílica. El ejercicio terapéutico (ET) es el principal tratamiento realizado; con este se obtuvieron mejoras significativas en distintas variables físicas.

ABSTRACT Introduction: Haemophilic arthropathy presents with different important clinical disorders, such as joint disease, pain, decreased range of motion, and functional alterations that can produce limitations in functionality and mobility. The physical exercise adapted to patients with haemophilia can be an adequate therapeutic strategy, having a positive impact on the quality of life of these subjects. Objectives: To identify the published clinical trials that evaluate the efficacy of physical rehabilitation in the treatment of haemophilic arthropathy. Materials and methods: A systematic review and meta-analysis of clinical trials was con ducted (using pre-defined eligibility criteria). The literature search was performed in the databases: PEDro, Pubmed, Scopus, and Web of Science. The quality of the methods used in the studies was evaluated using the PEDro scale. Results: After applying the inclusion and exclusion criteria, 7 studies were included in this review, providing favourable results on muscle strength and circumference, range of motion, joint disease, and quality of life. Moreover, 2 articles contributed information to the meta-analysis, showing favourable results on pain [Standardised mean difference (SMD) = -2.64; 95% CI: (-4.26; 1.03)]. Conclusions: This systematic review found evidence on the efficacy of physical rehabilitation in the treatment for haemophilic arthropathy. Therapeutic exercise is the main treatment carried out, obtaining significant improvements in the different physical outcomes.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

resumen está disponible en el texto completo

Abstract Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion transmitted infections) or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology charachterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.

Bloqueo de nervios periféricos guiados por ecografía en pacientes con hemofilia / Ultrasound-guided peripheral nerve blocks in hemophilia with patients

INTRODUCTION: Hemophilia is a coagulation disorder; it is a recessive disease linked to the X chromosome. In patients with hemophilia (PWH), regional anesthetic blocks have been considered a contraindication. Safety has been increased by performing them guided by Ultrasound. The objective of our work is to show our experience in PWH and peripheral nerve blocks. MATERIAL AND METHOD: 41 PWH were operated under regional analgesia with Ultrasound-Guided Peripheral Nerve Blocks associated with general anesthesia in the period 2006-2019. All patients were Hemophilia A. Three patients had inhibitors. The mean age was 35 years. 40 lower limb blocks and 2 upper limb blocks were performed. The Sonosite® equipment model Micromaxx was used. RESULTS: All patients presented adequate peripheral nerve block for an average time of 12.5 hours (8-24). There were no complications. CONCLUSIÓN: The present study shows that Ultrasound-Guided Peripheral Nerve Blocks in PCH is a safe procedure, which reduces the requirements of opioids and the side effects of them, improving the postoperative period and the recovery of patients.

INTRODUCCIÓN: La hemofilia es un trastorno de la coagulación, es una enfermedad recesiva ligada al cromosoma X. En pacientes con hemofilia (PCH) los bloqueos regionales anestésicos se han considerado una contraindicación. Se ha aumentado la seguridad realizándolos guiados por Ecografía. El objetivo de nuestro trabajo es mostrar nuestra experiencia en PCH y bloqueos de nervios periféricos. MATERRIAL Y MÉTODO: 41 PCH fueron operados bajo analgesia regional con Bloqueos de Nervios Periféricos Guiados por Ecografía asociado a la anestesia general en el período 2006-2019. Todos los pacientes eran hemofilia A. Tres pacientes presentaban inhibidores. La edad media fue de 35 años. Se realizaron 40 bloqueos de miembros inferiores y 2 bloqueos miembros superiores. Se utilizó el equipo Sonosite® modelo Micromaxx. RESULTADOS: Todos los pacientes presentaron adecuado bloqueo de nervio periférico durante un tiempo promedio de 12,5 h (8-24). No se presentaron complicaciones. CONCLUSIÓN: El presente estudio muestra que los Bloqueos de Nervios Periféricos Guiados por Ecografía en PCH es un procedimiento seguro, que reduce los requisitos de los opioides y los efectos secundarios de ellos, mejorando el posoperatorio y la recuperación de los pacientes.

Demographics and outcome of patients with congenital haemophilia in Sarawak, Malaysia

@#Introduction: Sarawak has a population that is geographically and characteristically widely varied. This study aimed to determine the demographic profile of patients in Sarawak, Malaysia. Materials and Methods – A cross-sectional study was conducted in 2019 at four major haemophilia treatment centres in Kuching, Sibu, Bintulu and Miri Hospitals, Sarawak. Demographic and clinical data were collected with consents from patients. Results and Discussion: Ninety-six haemophilia patients were identified - 79(82.3%) haemophilia A(HA) and 17(17.7%) haemophilia B(HB). Severe haemophilia patients were noted in 45.6% (36/79) of HA and 64.7% (11/17) of HB. In all 44.3% of the HA and 52.9% of the HB population had no identifiable family history of haemophilia. Two-thirds of the patients with severe HA were on prophylaxis [24/36 (66.7%)] and only onethird [4/11 (36.4%)] in severe HB. Inhibitors developed in 9/79 (11.4%) of the HA population [3/79 (3.8%) high responders]. The median inhibitor titre was not significantly different between the different treatment groups – on demand versus prophylaxis (1.0BU versus 2.0BU; z statistic -1.043, p-value 0.297, Mann-Whitney test). None of the patients developed inhibitory alloantibodies to factor IX. Four HA patients (5.1%) underwent immune tolerance induction where one case had a successful outcome. Three severe HA patients received emicizumab prophylaxis and showed remarkable reduction in bleeding events with no thromboembolic events being reported. One female moderate HA patient received PEGylated recombinant anti-haemophilic factor. Eleven patients underwent radiosynovectomy. One mild HB patient succumbed to traumatic intracranial bleeding. Our data reported a prevalence (per 100,000 males) of 5.40 cases for all severities of HA, 2.46 cases for severe HA; 1.16 cases for all severities of HB, and 0.75 cases for severe HB. The overall incidence of HA and HB was 1 in 11,500 and 1 in 46,000, respectively. Conclusion: This study outlines the Sarawakian haemophilia landscape and offers objective standards for forward planning. Shared responsibilities among all parties are of utmost importance to improve the care of our haemophilia population.

Haemophilia care and outcome in a major haemophilia treatment centre in Malaysia

@#Introduction/Objective: The management of potential treatment-related complications and bleeding events in haemophilia is challenging in developing countries. Providing optimal care among these patients improve their quality of life (QOL) and life expectancy. This study explores the demographic characteristics and treatment outcome in a major haemophilia treatment centre in Malaysia. Materials and Methods: A total of 260 patients were recruited in this retrospective cross-sectional analysis. Clinical data, including treatment regimens and outcome, were collected and analysed. Results: A total of 211 patients were diagnosed with haemophilia A (HA) (severe disease, 72.5%) and 49 patients had haemophilia B (HB) (severe disease, 65.3%). The median age was 31 (IQR;2-84) years. Majority of the patients had at least one episode of musculoskeletal bleeding since diagnosis. The mean annual bleeding event (ABE) was 4.91 (SD±6.07) in 2018. Target joints were identified in 80.4% of the patients. Chronic arthropathy and synovitis collectively accounted for more than half of the musculoskeletal complications. 30.1% of the patients had contracted hepatitis C with less than half received treatment. Thirty-one patients (16.8%) with severe haemophilia developed inhibitor and 12 patients successfully underwent immune tolerance induction. More than three-quarters of the severe haemophilia patients were treated with factor concentrate prophylaxis. The mean prophylaxis dose for HA and HB were 41.3 (SD±19.1) and 48.6 (SD±21.5) IU/kg/week, respectively. In patients with severe disease, prophylaxis significantly reduced the ABE (5.45,9.03;p=0.005). Conclusion: The importance of utilising a low to moderate dose regimen as prophylaxis in haemophilic patients is highlighted in our study. Future studies should include QOL assessment will further improve the management in haemophilia.

Primera experiencia de tratamiento con emicizumab en un paciente con hemofilia A severa e inhibidor de alto título en Uruguay / First report of emicizumab use in a patient with severe haemophilia A and high-titer inhibitor in Uruguay / Primeira experiência de tratamento com emicizumab em paciente com hemofilia A grave e inibidor de alto título no Uruguai

La hemofilia A es una coagulopatía congénita causada por la deficiencia o el mal funcionamiento del factor VIII de la coagulación. Una de las complicaciones más graves del tratamiento de la hemofilia A es el desarrollo de inhibidores que hacen que la terapia de reemplazo con FVIII sea ineficaz, dificultando la prevención y el control de los sangrados. El emicizumab es un anticuerpo monoclonal humanizado biespecífico dirigido contra los factores FIXa y FX, que imita la función de cofactor del FVIII. El tratamiento profiláctico con emicizumab es seguro y eficaz para prevenir hemorragias en los pacientes con hemofilia A con y sin inhibidores. Se presenta el caso del primer paciente tratado con emicizumab en Uruguay.

Haemophilia A is a congenital coagulopathy caused by a deficiency or malfunction of coagulation factor VIII. One of the most serious complications of haemophilia A treatment is the development of inhibitors that render FVIII replacement therapy ineffective, making it difficult to prevent and control bleeding. Emicizumab is a humanized bispecific monoclonal antibody directed against factors FIXa and FX, which mimics the cofactor function of FVIII. Emicizumab has been shown to be safe and effective as prophylaxis to prevent bleeding in haemophilia A patients with or without inhibitors to FVIII. We report the first patient treated with emicizumab in Uruguay.

A hemofilia A é uma coagulopatia congênita que se caracteriza pela ausência ou mau funcionamento do factor VIII da coagulação. Uma das complicações mais sérias do tratamento da hemofilia A é o desenvolvimento de inibidores que tornam a terapia de reposição do FVIII ineficaz, dificultando a prevenção e o controle do sangramento. O emicizumab é um anticorpo monoclonal biespecífico humanizado dirigido contra os fatores FIXa e FX, que imita a função de cofator do FVIII. O tratamento profilático com emicizumab é seguro e eficaz na prevenção de sangramento em pacientes com hemofilia A com e sem inibidores. É apresentado o caso do primeiro paciente tratado com emicizumabe no Uruguai.

Validación del ensayo FVIII: C cromogénico en una plataforma automatizada

El objetivo de este trabajo fue realizar la validación analítica del método cromogénico (FVIII:Ccro) en la plataforma ACL TOP y correlacionarlo con el método coagulable en una etapa (FVIII:Ccoag). El estudio de validación (EP5-A2, EP6-A2 y comparación de métodos por EP-9) se realizó para la curva de rango normal-bajo (CRNB): aproximadamente entre 10-150 UI/dL de FVIII y de rango muy bajo (CRMB): aproximadamente entre 0-10 UI/dL. Los resultados de repetitividad (CVr) y precisión intermedia (CVi) fueron menores del 6% y comparables a los informados por el fabricante para otras plataformas. El rango de medición analítica fue de 11-129 UI/dL con CRNB, y se extrapoló a 0,3 UI/dL al utilizar la CRMB. Para la CRNB FVIII:Ccro mostró buena correlación con FVIII:Ccoag: r: 0,98, pendiente: 0,982 (0,961-1,003), ordenada al origen: -0,3 (-1,1-0,5), sesgo: -2,0%. Para CRMB se obtuvo un r de 0,96, pendiente: 0,921 (0,855-0,988), ordenada al origen: -0,07 (-0,35-0,20), sesgo: -10,2%. Sólo 4 pacientes presentaron niveles discrepantes entre ambos métodos. La determinación de FVIII:C por el método cromogénico automatizado en la familia ACL TOP fue comparable con FVIII coagulable en una etapa en el rango analítico evaluado. El FVIII:Ccro automatizado puede utilizarse para el diagnóstico y seguimiento del tratamiento de los pacientes hemofílicos.

The objective of this work was to perform the analytical validation of the chromogenic method (FVIII:Ccro) on the ACL TOP platform correlating with one stage assay (FVIII:Ccoag). The validation study (EP5-A2, EP6-A2 and comparison of methods by EP-9) was performed for the low-normal range curve (CRNB): approximately between 10-150 IU/dL of FVIII and very low range (CRMB): approximately between 0-10 IU/dL. The results of CVr (repeatability) and CVi (intermediate precision) were lower than 6% and comparable to those reported by the manufacturer for other platforms. The analytical measurement range was 11-129 IU/dL, extrapolated to 0.3 IU/dL using the CRMB. For CRNB FVIII:Ccro showed good correlation with FVIII:Ccoag: r: 0.98, slope: 0.982 (0.961-1.003), intercept: -0.3 (-1.1-0.5), bias: -2.0%. For CRMB: r: 0.96 was obtained, pending: 0.921 (0.855-0.988), intercept: -0.07 (-0.35-0.20), bias: -10.2%. Only 4 patients presented discrepant levels between both methods. The automated chromogenic FVIII assay in the ACL TOP family is comparable with one stage coagulable FVIII in the analytical range studied. The FVIII:Ccro automated can be used for the diagnosis and monitoring of the treatment of hemophilic patients.

O objetivo deste trabalho foi a validação analítica do método cromogênico (FVIII:Ccro) na plataforma ACL TOP correlacionando-se com o método coagulável numa etapa (FVIII:Ccoag). O estudo de validação (EP5-A2, EP6-A2 e comparação de métodos por EP-9) foi realizado para a curva de faixa normal-baixa (CRNB) aproximadamente entre 10 e 150 Ul/dL de FVIII e de faixa muito baixa (CRMB): aproximadamente entre 0 e 10 UI/dL. Os resultados de Repetitividade (CVr) e precisão intermediária (CVi) foram inferiores a 6% e comparáveis aos descritos pelo fabricante para outras plataformas. A faixa de medição analítica foi de 11-129 UI/dL com CRNB extrapolando-se para 0,3 UI/dL utilizando a CRMB. Para a CRNB FVIII:Ccro houve boa correlação com o FVIII: Ccoag: r: 0,98, inclinação: 0,982 (0,961-1,003), ordenada na origem: -0,3 (-1,1-0,5), Viés: -2,0%. Para CRMB: foi obtido um r: 0,96, pendente: 0,921 (0,855-0,988), ordenado na origem: -0,07 (-0,35-0,20), Viés: -10,2%. Apenas quatro pacientes apresentaram níveis discrepantes entre os dois métodos. A determinação de FVIII:C pelo método cromogênico automatizado na família ACL TOP foi comparável ao FVIII coagulável em um estágio na faixa analítica avaliada. FVIII: O FVIII:Ccro automatizado pode ser utilizado para o diagnóstico e seguimento do tratamento dos pacientes hemofílicos.

Clinical Spectrum of Intracranial Bleeds in Patients with Bleeding Disorders- Experience from a Tertiary Center in Karnataka.

The most frequent emergency event in haemophilia and other bleeding disorders is intracranial haemorrhage (ICH), most of which is caused by trivial trauma, affecting around 3–10%. We studied the spectrum of presentation of ICH at our institute.METHODSThis was retrospective analysis of all patients with diagnosed or suspected bleeding diathesis and ICH presenting at the Clinical Haematology Department, BMCRI. They underwent complete coagulation workup, inhibitor screening, plain CT- brain and other relevant investigations.RESULTS3.26% of patients with bleeding disorders presented with ICH of over 2 years. M:F ratio was 13:1. 78.6% had Haemophilia A, 7.1% each had Haemophilia B, Factor XIII deficiency and Hypofibrinogenemia. 13 (92.9%) had severe Haemophilia A or B and 1 (7.1%) had mild Haemophilia B. Their ages ranged from 2 - 69 years. 50% were adults with the oldest being 69 years. Out of 7 children with Intracranial bleeds, 5 (71.4%) were <5 years. 2 (18.2%) with Haemophilia A had inhibitors. None were hypertensive. There was recent history of trauma in 9 (64.3%). All (100%) had severe headache, 21.4% had vomiting and 28.6% had seizures at presentation. Subdural haemorrhage was seen in 9 (64.3%), subarachnoid haemorrhage in 1 (7.1%), epidural bleed in 1 (7.1%), and intraparenchymal bleed in 3 (21.4%). All patients received appropriate factor replacement and supportive treatment. 9 (64.3%) received factor replacement only, 5 (35.7%) with SDH required additional burr hole evacuation. 2 (14.3%) patients died and 12 (85.7%) responded to treatment. None had sequelae in this series.CONCLUSIONS3.26% of our cohort presented with intracranial bleed over a period of two years. Majority with ICH were Haemophilia A and had severe deficiency with history of trauma. Headache is the commonest presentation and astute and keen clinical suspicion is paramount for instituting early treatment. SDH was most common in our series and majority responded to conservative management with factors.

Management of pseudo tumour in haemophilia patients

A hemophilic pseudotumor is one of the rare complications of hemophilia that results from repetitive bleeding, forming an expanding destructive encapsulated hematoma and necrosed tissue. It has a considerable amount of morbidity. These have become rare over the years with better treatment modalities like factor replacement. Presently, excision is the preferred treatment by many authors. There are instances where surgical excision is not feasible. In such situations, radiotherapy and arterial embolization should be considered either alone or as an adjunct to surgery. A 32 years old male patient, with severe hemophilia A diagnosed with an abdominal tumour 7 years ago during routine screening, that progressively grew to encompass the lower abdominal area. A 44 years old male patient with hemophilia A presented with slow growing swelling over the left gluteal region since, 10 years associated with ulceration and bleeding since, 3 days. The management of a patient with a haemophilic pseudo tumour is complex, with a high rate of potential complications. Surgical excision is the treatment of choice but can only be carried out by a multidisciplinary surgical team. The main postoperative complications are rebleed, infection, fistula and pathological fractures. Pelvic pseudo tumours can even become complicated by fistula formation to the large bowel and by obstruction of the ureters. Untreated pseudo tumours will ultimately destroy soft tissues, erode bone, and may produce neurovascular complications. The hemophilic pseudo tumour is a rare entity which is slow growing painless tumour, with few reports worldwide in the management of this rare complication.

Nutritional status and growth of children with hemophilia: a cross-sectional study

Background: Haemophilia A and B are the most common severe bleeding disorders and are inherited as X linked recessive pattern. The main clinical manifestations include bleeding into musculoskeletal sites or soft tissues mainly causing joint impairment and thus resulting in various morbidities. Prophylaxis therapy and inhibitor management have contributed a lot to the management of haemophilia cases. However in resource poor setting countries, like India, availability of factors, prophylactic therapy is farfetched leading to joint abnormalities, decreased physical activity and thus leading to different nutritional states. Studies from developed countries reveal obesity and overweight instances in children with Hemophilia. However not many studies have been undertaken to evaluate the nutritional status of such children in India.Methods: This study was conducted in the Comprehensive hemophilia Care Centre, Victoria Hospital, attached to Bangalore Medical College. A total of 50 children were included in the study. Children aged between 4 and 18 years attending the hemophilia Clinic were included in the study. Observations and review of relevant documents were done.Results: Among 50 children of haemophilia, 18(36%) children were aged less than 10 years and 32(64%) children were aged more than 10 years. The mean age of onset of disease in haemophilia A was 27.5 months (SD of 24.84; range 6-120) and in haemophilia B was 8 months (SD of 2.72; range 3-12). The mean BMI among children aged more than 10 years was more (21.35; SD= 4.02) compared to the children less than 10 years (16.87; SD= 3.41).Conclusions: The prevalence of overweight and obesity among children with Haemophilia is more in adolescent age group compared to children in the first decade.

Screening and quantitative estimation of factor VIII inhibitors by Nijmegen-Bethesda assay in hemophilia a patient of Southern Odisha, India

Background: The current treatment of haemophilia is replacement of factor VIII or IX which is effective till development of inhibitor against factors. There has been no study on factor VIII inhibitors in Southern Odisha using Nijmegen朆ethesda assay. This study was planned with objectives to screen factor VIII inhibitors in hemophilia-A patients, to do quantitative estimation of it using Nijmegen-Bethesda assay and to explore factors associated with development of inhibitors. Methods: This cross-sectional study was carried out from September 2016 to August 2018 in Department of pathology, MKCG medical college, Berhampur. Haemophilia-A patients coming to MKCG medical college and registered Haemophilia-A cases under Haemophilia society of Berhampur were included. Patients denying consent and having multiple clotting factors deficiencies were excluded. 1.8ml blood was collected. Mixing study was done to screen factor VIII inhibitors and then in positive cases inhibitors level measured by Nijmegen-Bethesda method. All data were analysed using SPSS (version 16.0).Results: 70 cases of Hemophilia-A patients were studied. Majority (50%) were with severe hemophilia-A. 7 patients developed inhibitors where 3 were high and 4 were low responders. Inhibitor level ranged from 0.8 to 64 Nijmegen-Bethesda units. Patients with severe hemophilia A, more than 10 transfusions and who switched to receive recombinant FVIII from other blood products developed inhibitors which were significant.Conclusions: Severity of hemophilia, increase frequency of transfusion and switching of blood products significantly increases chances of inhibitor development and hence intensive inhibitor screening is needed in these cases. Quantification of inhibitor is needed to monitor treatment and to manage bleeding episodes effectively.

Clinico-Haematological Profile of Haemophilia in Patients Attending Gandhi Medical College and Associated Hamidia Hospital, Bhopal..

BACKGROUND Haemophilia A and haemophilia B are the commonest form of haemophilia encountered and they result from a defect in Factor VIII and Factor IX gene respectively. This hinders the process of haemostasis and predisposing haemophiliacs to spontaneous or post traumatic bleeding. We wanted to study the clinico-haematological profile of patients with haemophilia.METHODSThis observational study was conducted in Gandhi Medical College and Associated Hamidia Hospital, Bhopal, during the period of March 2017 to June 2018. After clinical evaluation, patients were subjected to a battery of coagulation tests (Bleeding Time, Prothrombin Time, Activated Partial Thromboplastin Time, Correction Studies and whenever possible, Specific Coagulation Factor Assay). The results were analysed.RESULTSDuring the study period, 100 patients of haemophilia were studied. Majority of patients were of haemophilia A (89%). Most common age group was 6 - 15 years (49%) and mean age was 19.02±12.58 years. Most common age of onset was <1 year (62%). Positive family history was present in 57% of cases. 52% patients had severe haemophilia. Most common presentation was haemarthrosis & knee joint was the most common joint involved. APTT was prolonged in all cases.CONCLUSIONSHaemophiliacs are distributed worldwide and have heterogeneous presentation depending upon disease severity. Knowledge of the spectrum of presentation of haemophilia in the population helps in early diagnosis and management planning. Promotion of regular availability of factor concentrate, establishing comprehensive care center and positive public awareness along with good haematology laboratory will help in achieving outcome comparable to that of developed countries.

The study of disease pattern of various clinical classes of hemophilia in South Gujarat area, India

Background: Haemophilia is one of the most severe bleeding disorder. Seventy-five per cent of the global haemophiliacs live in developing countries, where probably only one in five cases is diagnosed, and there is little or no care available. Haemophilia as a disease and its management has a large impact on the community, including social integration and economics. Inability to be an active part of society and high cost of the medical care make this disease an important problem for all haemophilic patients.Methodology: a cross-sectional study, conducted over a period of one and half year. Institutional Ethics Committee permission was taken before starting the study. Information was gathered through personal interview of the patient's guardian with the help of predesigned questionnaires. Special emphasis was given to past history of bleeding. For each specific symptom/ specific site a detailed history and relevant details was taken and number of episodes of each symptom or number of episodes of involvement of a specific site was written.Observations: Out of 75 patients of haemophilia; 8 (10.7%) were Mild haemophilic, 17 (22.7%) were moderate haemophilic; and 50 (66.7%) were severe haemophilic. Most common site for spontaneous bleeding was muscle where 121 (25%) episodes of bleeding were reported, followed by knee joint 97(20%), and Ankle 79 (16.3%). The commonest site for traumatic bleeding was muscle where 201 (24.7%) episodes of bleeding were reported, followed by knee joint 175 (21.5%), Ankle 143 (17.6%) and Elbow joint 83 (10.2%). Site with highest duration of bleeding was intracranial for 6 days.Conclusion: Frequency of traumatic dental and nasal bleeds was significantly higher in mild class as compared to moderate and severe classes. In severe category Knee, ankle, elbow and muscle were the commonest site where traumatic bleeding. There was no significant difference in bleeding frequencies at various sites in moderate and severe cases, whether spontaneous or traumatic bleed.

Epidemiology, spectrum of clinical manifestations and diagnostic issue of acquired haemophilia: A case series

@#Introduction: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder caused by polyclonal immunoglobulin G autoantibodies against clotting factor VIII (FVIII). The incidence was reported to be rare occurring in 0.2- 4 cases/million/year. Patients may present with different clinical manifestations to various specialties. Early recognition of the disease contributes to favourable clinical outcome. Case Series: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention. Discussion: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.