RESUMEN
Agranulocytosis and aplastic anaemia associated with sulphasalazine are well recognised, but pancytopenia caused by acute megaloblastic arrest of haemopoiesis while taking sulphasalazine has not previously been described. We report three patients who, after taking sulphasalazine for over two years, suddenly developed severe pancytopenia with gross megaloblastic changes in the marrow. In two patients there was a good response to high dose oral folic acid but the third required folinic acid. The mechanism appears to be acute folate deficiency, and the requirement for folinic acid in one case suggests that the known inhibition of folate metabolism by sulphasalazine also contributes. The syndrome appears to be associated with high dosage and slow acetylator status. The drug has been successfully restarted at reduced dosage with folate supplements in two patients both of whom were slow acetylators. In the third case, whose acetylator status is not known, progression of her disease led to colectomy.
Asunto(s)
Deficiencia de Ácido Fólico/complicaciones , Pancitopenia/etiología , Sulfasalazina/efectos adversos , Adolescente , Adulto , Médula Ósea/patología , Femenino , Ácido Fólico/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Pancitopenia/tratamiento farmacológico , Pancitopenia/patologíaAsunto(s)
Anticoagulantes/uso terapéutico , Tromboembolia/prevención & control , Administración Oral , Instituciones de Atención Ambulatoria , Anticoagulantes/administración & dosificación , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en HospitalRESUMEN
The serum of an 84 year old man with disseminated carcinoma was found to contain extremely high concentrations of cobalamin and of a cobalamin binding protein with trans-cobalamin I characteristics. Tumour tissue samples obtained at necropsy contained considerably higher concentrations of cobalamin binding protein (R-binder) than normal tissues. Tumour tissues also contained increased concentrations of specific folate binding protein. In all tissues studied a close correlation existed between unsaturated cobalamin and unsaturated folate binding and between total cobalamin and total folate binding. These results suggest related mechanisms for the synthesis of cobalamin binding proteins of the R-binder class and folate binding proteins by tumour tissue.
Asunto(s)
Carcinoma/metabolismo , Proteínas Portadoras/metabolismo , Ácido Fólico/metabolismo , Receptores de Superficie Celular/metabolismo , Transcobalaminas/metabolismo , Anciano , Receptores de Folato Anclados a GPI , Humanos , Masculino , Vitamina B 12/metabolismoAsunto(s)
Hemoglobinas Anormales , Adulto , Secuencia de Aminoácidos , Aminoácidos/análisis , Arginina , Femenino , Humanos , Fragmentos de Péptidos/análisis , Treonina , TripsinaRESUMEN
A myeloproliferative disorder, similar to agonogenic myeloid metaplasia, has been described in patients with cancer. Two patients with carcinoma of the lung are described who presented with such a disorder but in whom there was no evidence of bone marrow fibrosis and in one of whom there was no evidence of bone marrow infiltration by tumor. The possible mechanism of this association is discussed.