RESUMEN
Factor V is an essential clotting factor that plays a key role in the blood coagulation cascade on account of its procoagulant and anticoagulant activity. Eighty percent of circulating factor V is produced in the liver and the remaining 20% originates in the α-granules of platelets. In humans, the factor V gene is about 80 kb in size; it is located on chromosome 1q24.2, and its cDNA is 6914 bp in length. Furthermore, nearly 190 mutations have been reported in the gene. Factor V deficiency is an autosomal recessive coagulation disorder associated with mutations in the factor V gene. This hereditary coagulation disorder is clinically characterized by a heterogeneous spectrum of hemorrhagic manifestations ranging from mucosal or soft-tissue bleeds to potentially fatal hemorrhages. Current treatment of this condition consists in the administration of fresh frozen plasma and platelet concentrates. This article describes the cases of two patients with severe factor V deficiency, and of their parents. A high level of mutational heterogeneity of factor V gene was identified, nonsense mutations, frameshift mutations, missense changes, synonymous sequence variants and intronic changes. These findings prompted the identification of a new mutation in the human factor V gene, designated as Jaén-1, which is capable of altering the procoagulant function of factor V. In addition, an update is provided on the prospects for the treatment of factor V deficiency on the basis of yet-to-be-developed recombinant products or advanced gene and cell therapies that could potentially correct this hereditary disorder.
Asunto(s)
Análisis Mutacional de ADN , Deficiencia del Factor V/genética , Deficiencia del Factor V/terapia , Factor V/genética , Adolescente , Coagulación Sanguínea , Trastornos de la Coagulación Sanguínea Heredados/genética , Pruebas de Coagulación Sanguínea , Plaquetas/metabolismo , Preescolar , Codón sin Sentido , ADN Complementario/metabolismo , Salud de la Familia , Femenino , Mutación del Sistema de Lectura , Humanos , Masculino , Pakistán , Proteínas Recombinantes/química , Análisis de Secuencia de ADN , EspañaRESUMEN
A 17-year-old male presented with gradual painless diminution of vision since childhood. Slit lamp examination revealed both eyes having congenital cataract. Right eye lens aspiration was performed but was uneventful, and he prepared for left eye surgery after 7 days. Immediately after giving a peribulbar block, a complete akinesia, tight eyelids, and stony hard eyeball was noted. An abaxial proptosis of 7 mm was noted. Lateral canthotomy and inferior cantholysis were done and proptosis reduced to 5 mm. Bleeding time-clotting time was normal. Proptosis worsened to 8 mm the next day. Contrast-enhanced computed tomography scan showed inferolateral subperiosteal hematoma, but drainage could not be performed due to prolonged prothrombin time and activated prothrombin time. Fresh frozen plasma was transfused. Tarsorrhaphy was performed for exposure keratopathy after his coagulation profile became normal. Hematology evaluation after 2 weeks detected factor V deficiency, and was diagnosed as Owren's disease or parahemophilia.
RESUMEN
A case of Factor V deficiency, the first case in Korea, is reported in a 9-year-old boy whose plasma concentration of Factor V was 6%. He complained of easy bruisability, prolonged bleeding from the mouth after minor trauma and hemarthrosis and flexion contracture of the right knee. His parents are heterozygous (maternal Factor V concentration 52%, paternal 40%).