Hemofilia A: una enfermedad huérfana / Hemophilia A: a rare disease

La hemofilia A es una enfermedad hereditaria ligada al cromosoma X, causada por mutaciones en el gen F8 del factor VIII de la coagulación. Se considera una enfermedad huérfana, ya que su prevalencia es baja, de 26,6 por cada 100.000 nacidos vivos de sexo masculino. Los pacientes con hemofilia A tienen fases de inicio y amplificación de la coagulación relativamente normales y son capaces de formar el tapón plaquetario inicial en el lugar de la hemorragia, pero debido a la deficiencia del factor VIII, son incapaces de generar una cantidad de trombina en la superficie de las plaquetas, que sea suficiente para estabilizar el coágulo de fibrina. En un paciente masculino con hemorragias inusuales debe descartarse un trastorno de coagulación tipo hemofilia A, y se debe solicitar un recuento de plaquetas y un tiempo de protrombina (TP), los cuales usualmente son normales, y un tiempo de tromboplastina parcial activado (TPT) que se presenta prolongado. Para el diagnóstico diferencial con otras coagulopatías se realiza la medición de factores de coagulación, y pruebas de corrección cuando existe la sospecha de un inhibidor o de una hemofilia adquirida. Los pacientes afectados pueden presentar formas leves, moderadas o severas de la enfermedad, según el nivel plasmático del factor. En Colombia y en el mundo, la hemofilia fue reconocida como una enfermedad huérfana que representa un problema de salud pública, debido a su proceso de atención altamente especializado, que incrementa los costos asociados con la asistencia sanitaria, y afecta la calidad de vida de los pacientes y de aquellos que los rodean, además de que representa un reto diagnóstico que requiere constante actualización, para que pueda ser tratada de manera efectiva

Hemophilia A is an X-linked inherited disease caused by mutations in the coagulation factor VIII F8 gene. It is considered a rare disease, as its prevalence is 26.6 per 100,000 live male births. Patients with hemophilia A have a relatively normal coagulation onset and amplification phases, and are able to form the initial platelet plug at the site of hemorrhage; but due to factor VIII deficiency, they are unable to generate a sufficient amount of thrombin on the platelet surface to stabilize the fibrin clot. In a male patient with unusual bleeding, a hemophilia A-type coagulation disorder should be ruled out, and blood tests such as a platelet count and prothrombin time (PT), which are usually normal, and an activated partial thromboplastin time (APTT), which is prolonged, should be requested immediately. For differential diagnosis with other coagulopathies, measurement of coagulation factors and correction tests are performed when there is suspicion of an inhibitor or acquired hemophilia. Affected patients may present mild, moderate or severe forms of the disease, depending on the plasma level of the factor. In Colombia and worldwide, hemophilia was recognized as a rare disease that represents a public health problem due to its highly specialized care, which increases the costs associated with health care, and affects the quality of life of patients and those around them, as well as representing a diagnostic challenge that requires constant updating, so that it can be treated effectively

Life-threatening hemorrhage secondary to acquired deficiency of coagulation factors VIII and XI related to systemic lupus erythematosus: case report / Hemorragia severa secundaria a deficiencia adquirida de factores VIII y XI de la coagulación relacionada con lupus eritematoso sistémico: reporte de caso

ABSTRACT In patients with autoimmune diseases, the simultaneous occurrence of lupus anticoagulant and blood coagulation factors inhibitors is infrequent and is associated with hemorrhagic events. In these cases, the initial approach requires a thorough interpretation of coagulation laboratory tests and mixing studies to reach a definitive diagnosis. We report the case of a patient with systemic lupus erythematosus and Sjögren's syndrome who presented with hemorrhagic diathesis caused by circulating inhibitors against factors VIII and XI coexisting with lupus anticoagulant. The inhibitors eradication was made with rituximab, achieving good results.

RESUMEN La ocurrencia simultánea de anticoagulante lúpico e inhibidores circulantes contra los factores de la coagulación es infrecuente en los pacientes con enfermedad autoinmune, y está relacionada con eventos hemorrágicos. El abordaje inicial requiere una adecuada interpretación de los tiempos de coagulación y prueba de mezcla con plasma para alcanzar el diagnóstico definitivo. Se reporta el caso de una paciente con lupus eritematoso sistémico y síndrome de Sjögren, quien se presentó con trastorno hemorrágico amenazante de la vida ocasionado por inhibidores circulantes contra los factores VIII y XI de la coagulación en coexistencia con anticoagulante lúpico. El tratamiento de erradicación de los inhibidores se realizó con rituximab, con buenos resultados.

Consensus Statement of the Indian Academy of Pediatrics in Diagnosis and Management of Hemophilia

Justification: Despite having standard principles of management of hemophilia, treatment differs in various countries depending onavailable resources. Guideline for management of hemophilia in Indian setting is essential.Process: Indian Academy of Pediatrics conducted a consultative meeting on Hemophilia on 18th September, 2016 in New Delhi, whichwas attended by experts in the field working across India. Scientific literature was reviewed, and guidelines were drafted. All expertcommittee members reviewed the final manuscript.Objective: To bring out consensus guidelines in diagnosis and management of Hemophilia in India.Recommendations: Specific factor assays confirm diagnosis and classify hemophilia according to residual factor activity (mild 5-40%,moderate 1-5%, severe <1%). Genetic testing helps in identifying carriers, and providing genetic counseling and prenatal diagnosis.Patients with hemophilia should be managed by multi-specialty team approach. Continuous primary prophylaxis (at least low-doseregimen of 10-20 IU/kg twice or thrice per week) is recommended in severe hemophilia with dose tailored as per response. Factorreplacement remains the mainstay of treating acute bleeds (dose and duration depends on body weight, site and severity of bleed).Factor concentrates (plasma derived or recombinant), if available, are preferred over blood components. Other supportive measures(rest, ice, compression, and elevation) should be instantly initiated. Long-term complications include musculoskeletal problems,development of inhibitors and transfusion-transmitted infections, which need monitoring. Adequate vaccination of children withhemophilia (with precautions) is emphasized

Características clínicas y epidemiológicas de pacientes con hemofilia del eje cafetero, Colombia / Clinical and epidemiological characteristics of patients with Haemophilia from coffee region, Colombia

INTRODUCCIÓN: La hemofilia es un trastorno hemorrágico hereditario, ligado al cromosoma X, con una prevalencia estimada de 8,4 casos de hemofilia A y 2,7 casos de hemofilia B por cada 100 000 hombres. OBJETIVO: Describir características sociodemográficas, clínicas y percepción del efecto de la patología en el paciente. MATERIALES Y MÉTODOS: Se realizó un estudio transversal, en pacientes con diagnóstico de hemofilia. La fuente de información fueron las historias clínicas, además de una encuesta aplicada para actualizar la caracterización clínica y epidemiológica, el análisis estadístico fue realizado con el software Stata versión 14®. RESULTADOS: 48 pacientes fueron incluidos en el estudio, el 97,9% presenta hemofilia tipo A, de los cuales el 12,5%, 43,8% y 41,7% son leve, moderada y severa respectivamente. El 35% de los pacientes con hemofilia severa desarrollaron anticuerpos contra el factor VIII. El 66% de los pacientes ha presentado alguna manifestación de la patología en los últimos seis meses y el 61,7% refieren que ha tenido un impacto negativo en algún aspecto de su vida. CONCLUSIONES: Los factores asociados a un requerimiento mayor de dosis del factor para el control de la patología fueron antecedente de sangrado, mayor edad y el desarrollo de inhibidores. Los pacientes con hemofilia severa presentaron desarrollo de inhibidores en un 30%, frente a la moderada y leve con un 3 y 0,3% respectivamente.

INTRODUCTION: Hemophilia is an inherited bleeding disorder, linked to the X chromosome, with an estimated prevalence of 8,4 cases of hemophilia A and 2.7 cases of hemophilia B per 100 000 men. OBJETIVE: To describe sociodemographic, clinical characteristics and perception of the effect of the pathology in the patient. MATERIAL AND METHODS: A descriptive cross-sectional study was conducted with patients diagnosed with hemophilia. The required information was extracted from each patient's medical history, additionally, each patient completed a questionnaire to update the clinical and epidemiological information. The analysis was realized in Stata version 14®. RESULTS: From the 48 patients included in the study, 97,9% have type A hemophilia, of whom 12,5%, 43,8% and 41,7% are mild, moderate and severe respectively. 35% of patients with severe hemophilia have developed antibodies against factor VIII. 66% of patients presented some manifestation of the disease in the last six months and 61,7% had a negative impact on some aspect of their life. CONCLUSION: Factors associated with a higher dose requirement of factor for pathology control were antecedent bleeding, increased age and inhibitor development. Patients with severe hemophilia had development inhibitors in 30%, compared to moderate and mild with 3 and 0.3%, respectively.

Cranial Hemophilic Pseudotumor: Case Report

Hemophilic pseudotumor is an uncommon, but characteristic complication of hemophilia occurring in 1% to 2% of individuals with a severe factor VIII or IX deficiency. Most of these lesions are located in the long bones and the pelvis. The authors describe a case of cranial hemophilic pseudotumor in a patient who presented with symptoms of headache and palpable mass on the occipital area. He was a 22 years old man with a two year history of severe factor VIII deficiency.

A Case of Combined Congenital Deficiency of Factor V and Factor VIII

Hemorrhagic disease of newborn by combined blood clotting factor deficiencies is very rare. Combined deficiency of factor V and factor VIII is the most common form among these cases, and inherited by autosomal recessive trait. Clinical findings are easy bruising, post-traumatic bleeding and bleeding after tooth extractions, and the main laboratory findings are prolonged partial thromboplastin time (PTT) and prothrombin time (PT) that are different from hemophilia A only with prolonged PTT. We experienced a case of combined congenital deficiency of factor V and factor VIII in a 1-day-old boy. We report the case with brief review of literature.

Comprehensive clinical and statistical analysis of hemophilia in Korea

A Total of 498 cases of hemophilia which were reported by sixteen medical centers in Korea were reviewed and analyzed. Hemophilia A comprised 425 cases (85.3%) and the remaining 73 cases (14.7%) were hemophilia B. One case was female and all other cases were male. There were known hemophilia patients in the family in 43.0% of cases and the involved members were brothers, maternal cousins, maternal uncles, and maternal grandfathers in descending order of frequency. The major symptoms of the patients were hemorrhagic, such as easy bruising and hemarthrosis followed by prolonged bleeding after trauma and soft tissue hematoma. The incidence of hemarthrosis increased significantly with age. The pediatric age group below the age of 15 consisted of 67.1% of the cases. According to the age at diagnosis, half (54.2%) of the severe cases were diagnosed before the age of 1 year. APTT was prolonged over 40 seconds in all cases and 291 cases showed severe prolongation over 80 seconds. Of 498 cases 273 cases (54.8%) belonged to the severe form (factor VII or IX level, less then 1%), whereas 182 cases (36.5%) and 43 cases (8.7%) belonged to the moderate (factor VIII or IX, 2-5%) and mild form (factor VIII or IX, 6-25%), respectively, Chronic arthropathy was present in 236 cases (49.6%), and the incidence increased significantly with age. The management of chronic arthropathy most commonly employed was rehabilitation in 25.4% of cases, but in 50.8% no management was given at all. The involved joints in descending order of frequency were knees, elbows and ankles. The complications were intracranial hemorrhage, Gl bleeding and nerve palsy in 48, 24, and 13 cases, respectively.

Comprehensive clinical and statistical analysis of hemophilia in Korea

A Total of 498 cases of hemophilia which were reported by sixteen medical centers in Korea were reviewed and analyzed. Hemophilia A comprised 425 cases (85.3%) and the remaining 73 cases (14.7%) were hemophilia B. One case was female and all other cases were male. There were known hemophilia patients in the family in 43.0% of cases and the involved members were brothers, maternal cousins, maternal uncles, and maternal grandfathers in descending order of frequency. The major symptoms of the patients were hemorrhagic, such as easy bruising and hemarthrosis followed by prolonged bleeding after trauma and soft tissue hematoma. The incidence of hemarthrosis increased significantly with age. The pediatric age group below the age of 15 consisted of 67.1% of the cases. According to the age at diagnosis, half (54.2%) of the severe cases were diagnosed before the age of 1 year. APTT was prolonged over 40 seconds in all cases and 291 cases showed severe prolongation over 80 seconds. Of 498 cases 273 cases (54.8%) belonged to the severe form (factor VII or IX level, less then 1%), whereas 182 cases (36.5%) and 43 cases (8.7%) belonged to the moderate (factor VIII or IX, 2-5%) and mild form (factor VIII or IX, 6-25%), respectively, Chronic arthropathy was present in 236 cases (49.6%), and the incidence increased significantly with age. The management of chronic arthropathy most commonly employed was rehabilitation in 25.4% of cases, but in 50.8% no management was given at all. The involved joints in descending order of frequency were knees, elbows and ankles. The complications were intracranial hemorrhage, Gl bleeding and nerve palsy in 48, 24, and 13 cases, respectively.