Hemofilia A adquirida: un diagnóstico de infarto / Acquired Hemophilia A: a heart attacking diagnosis

Resumen La hemofilia A adquirida es una entidad poco reportada y potencialmente fatal, que se asocia con la aparición de autoanticuerpos contra el factor VIII de la coagulación. Si bien puede estar subestimada, se calcula una incidencia aproximada de 1 a 1.5 casos por millón de habitantes con una mortalidad reportada entre el 9 y el 33%. Se manifiesta con equimosis extensas espontáneas y sangrado en mucosas, tracto gastrointestinal o en el periodo postparto. Se debe sospechar en adultos a partir de la cuarta década de la vida con sangrados espontáneos y un tiempo parcial de tromboplastina prolongado en ausencia de anticoagulante lúpico. Se reporta el caso de un adulto mayor con cardiopatía isquémica, en quien, en el contexto de un evento coronario agudo, se diagnosticó hemofilia A adquirida ante la presencia de sangrado subcutáneo extenso en cuello, con compresión de faringe y laringe que amenazó su vida representando un verdadero reto terapéutico.

Abstract Acquired hemophilia A is an underreported and potentially fatal entity that is associated with the formation of autoantibodies against coagulation factor VIII. Although it may be underestimated, the estimated incidence is between 1-1.5 cases per million people with a reported mortality between 9 and 33%2. It presents with extensive spontaneous ecchymosis, mucosal, gastrointestinal, or postpartum bleeding. It should be suspected in adults from the fourth decade of life with spontaneous bleeding and prolonged TPT in the absence of lupus anticoagulant. We report the case of an older adult with ischemic heart disease in the context of an acute coronary syndrome, who was diagnosed with acquired hemophilia A and presented with significant cervical subcutaneous bleeding with pharyngeal and laryngeal compression that threatened his life, constituting a real therapeutic challenge.

Consenso de hemofilia en México / Mexican Consensus in Haemophilia

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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.

Deficiencia adquirida del factor VIII. Un ejemplo cuando la cirugía puede ser perjudicial y no para salvar vidas / Deficiência adquirida do fator VIII. Um exemplo de quando a cirurgia pode ser prejudicial e nâo vinculada a salvar vidas / Acquired factor VIII deficiency. One instance when surgery may be harmful and not life-saving

La hemofilia adquirida A es una condición extremadamente rara que ocurre en una persona en un millón por año. Puede causar riesgo para la vida por causar episodios de sangrado durante la edad adulta, debido a la producción de auto-anticuerpos que inactivan el factor VIII. Su tratamiento suele incluir la inmunosupresión y la cirugía se debe evitar en lo posible. Presentamos dos casos que nos tocó tratar, y realizamos una recopilación somera de la bibliografia, a fin de enfatizar la necesidad de no realizar tratamiento quirúrgico en estos casos.

A hemofilia adquirida A é uma condição extremamente rara que pode ocorrer com a probabilidade de um caso em um milhão de pessoas por ano. Pode causar risco para a vida por causar episódios de sangramento durante a idade adulta, devido à produção de autoanticorpos que inativam o fator VIII. Seu tratamento geralmente inclui a imunosupressão, e a cirurgia deve, dentro do possível, ser evitada. Apresentamos dois casos por nós tratados, e realizamos um breve resumo da bibliografia, com a finalidade de enfatizar o propósito de não realizar tratamento cirúrgico nestes casos.

Acquired hemophilia A is an extremely rare disease with an incidence of 1 in 1,000,000 per year. It may be life threatening as it produces bleeding episodes in adult life, due to the production of antibodies which inactivate factor VIII. Treatment may include immunosuppression and surgery must be avoided as much as possible. We shall present two of our cases and then make a brief review of the literature, in order to underscore the need of not operating these cases.

Hemofilia A adquirida / Acquired hemophilia A

La hemofilia A adquirida (HAA) es un trastorno hemorrágico poco frecuente caracterizado por la presencia de autoanticuerpos contra el factor VIII (FVIII) circulante. Aproximadamente en la mitad de los casos se ha observado un grupo heterogéneo de procesos patológicos que incluyen, entre otros, enfermedades autoinmunes y malignas y durante el embarazo, parto y puerperio. Las manifestaciones hemorrágicas son variables y fundamentalmente de tipo cutáneo mucoso. El diagnóstico se basa en el hallazgo en un paciente con manifestaciones hemorrágicas, prolongación del tiempo parcial de tromboplastina activado (TPTA), disminución de la actividad del FVIII y presencia de inhibidores del FVIII. El tratamiento de HAA incluye el control de las manifestaciones hemorrágicas y la supresión de la producción del anticuerpo. El concentrado de factor VIIa recombinante (FVIIar) y el concentrado de complejo protrombínico (CCPA) se consideran el tratamiento antihemorrágico de primera línea. Como terapéutica alternativa, en algunos casos puede utilizarse el concentrado de FVIII, la plasmaféresis y la inmunoadsorción extracorpórea. La prednisona sola o asociada con la ciclofosfamida, constituye el tratamiento inmunosupresor de primera línea. En pacientes refractarios puede administrarse como terapéutica de segunda línea, el rituximab (anti-CD20). Con la azatiopina, la ciclosporina, la vincristina y el micofenolato de mofetil, se han obtenido resultados variables

Acquired hemophilia A (AHA) is an uncommon hemorrhagic disorder characterized by presence of autoantibodies to circulating factor VIII. Approximately in half of cases it is noted a heterogeneous group of pathological processes including among others, autoimmune and malignant diseases and during pregnancy, labor and puerperium. Hemorrhagic manifestations are variable and mainly of mucous cutaneous type. Diagnosis is based on the finding of a patient presenting with hemorrhagic manifestations, extension of activated partial thromboplastin time (APTT), decrease of Factor VIII activity, and presence of Factor VIII inhibitors. AHA treatment includes the control of hemorrhagic manifestations and the suppression of antibody production. The recombinant factor VIIIa (rVIIIaF) concentration and the prothrombin-complex concentrations (PCC) are considered like the first-line antihemorrhagic treatment. As alternative therapy in some cases the FCIII concentration, the plasmapheresis and extracorporeal immuno-adsorption may be used. The prednisone alone or associated with cyclophosphamide is the firs-line immunosuppressive treatment. In refractory patients it may be administered as a second-line therapy, the Rituximab (anti-CD20). With the use of Azathioprine, Cyclosporine, Vincristine and the Mycophenolate mofetil variable results have been achieved

Acquired hemophilia associated with rheumatoid arthritis / Hemofilia A adquirida associada à artrite reumatoide

O aparecimento do anticorpo contra fator VIII é um fenômeno bem estabelecido na hemofilia A, ocorrendo em 5 a 15 por cento dos pacientes hemofílicos dos Estados Unidos, Inglaterra, Suécia e França. Nos pacientes não-hemofílicos o seu aparecimento é raro, podendo ocorrer em indivíduos saudáveis, principalmente idosos e mulheres no puerpério, pacientes com neoplasia maligna ou doenças autoimunes, como lúpus eritematoso sistêmico, artrite reumatoide e síndrome de Sjõgren. Descrevemos o caso de uma paciente de 64 anos de idade, portadora de artrite reumatoide soropositiva há 23 anos, que há 10 dias desenvolveu equimoses e hematomas progressivos cuja investigação foi compatível com a presença de anticorpo contra fator VIII. Foi instituída terapia com metilprednisolona, ciclofosfamida endovenosa, imunoglobulina e reposição de complexo protrombínico, com remissão do quadro hemorrágico e negativação do anticorpo contra o fator VIII. Concluímos com esse caso que, apesar de ser rara, a presença de inibidores adquiridos do fator VIII deve ser pesquisada quando pacientes portadores de doença autoimune desenvolvem manifestações hemorrágicas associadas ao prolongamento do TTPA com TAP e contagem plaquetária normais.

The occurrence of the antibody against factor VIII is a well-known phenomenon in hemophilia A, occuring in 5 to 15 percent of the hemophilic patients in the United States, England, Sweden and France. The development of factor VIII in non-hemophilic patients is rare and may occur in healthy individuals, mostly elderly and women in postpartum period, and in patients with malignant neoplasia or autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and Sjõgren's syndrome. We described the case of a 64-year-old female patient who has had seropositive rheumatoid arthritis for 23 years and presented with a ten-day history of progressive ecchymosis. Therapy with methylprednisolone, intravenous cyclophosphamide, immunoglobulin and factor VIII reposition was instituted, resulting in a remission of the bleeding and negativity for antibodies against factor VIII titers. We concluded that, despite its rarity, the presence of acquired factor VIII inhibitors should be investigated when patients with autoimmune diseases develop bleeding manifestations.