Caracterización de tres mutaciones en el gen de la antitrombina / Identification of three mutations in the antithrombin gene

La antitrombina es el principal anticoagulante hemostático. Desde que el hematólogo Egeber descubriera en 1965 la primera deficiencia de antitrombina asociada a un aumento del riesgo trombótico, numerosos trabajos han identificado familias con deficiencia de antitrombina asociada a una significativa incidencia de trombosis venosa. Este trabajo recoge el estudio de 3 familias trombofílicas españolas con deficienciacongénita de antitrombina. En dos identificamos mutaciones en el gen de la antitrombina no descritas hasta la fecha: InsT7429-30 y Lys125Arg. En la tercera detectamos una variante, la antitrombina Cambridge II (Ala384Ser) identificada con elevada frecuencia en población británica. Valoramos su frecuencia en población española y su papel en el desarrollode trombosis venosa mediante un estudio de asociación caso-control en 1018 pacientes de trombosis venosa y 1018controles. Comprobamos que la antitrombina Cambridge II es una alteración no restringida a población británica, estando presente en el 0.2% de la población española pero en un 1.7% de los pacientes con trombosis venosa. Así, el alelo mutado incrementó 9.75 veces el riesgo trombótico. Además, esta mutación es la principal causa de deficiencia de antitrombina en pacientes con trombosis venosa. Finalmente destacamos que la antitrombina Cambridge II únicamente puede ser detectada por métodos moleculares. Todos estos resultados aconsejan el estudio de la antitrombina Cambridge II en los estudios trombofílicos rutinarios

Antithrombin is the most important haemostatic anticoagulant. Since, in 1965 Egeber described the first antithrombin deficiency associated with an increase of thrombotic risk, many studies have identified families with antithrombin deficiency that caused a significantly increase in the risk of venous thrombosis. We studied three thrombofilic families with congenital antithrombin deficiency. In two of them, we identified mutations in antithrombin gene not described previously: InsT7429-30 and Lys125Arg. In the third family, we detected a variant, antithrombin Cambridge II (Ala384Ser) that had a high frequency in British population. We have evaluated the prevalence of this mutation in Spanish population, and its role in venous thrombosis in a case-control study including 1018 patients with venous thrombosis and 1018 healthy controls. We confirmed that antithrombin Cambridge II is not restricted to British population, as we observed this mutation in 0.2% of Spanish population and in 1.7% of patients with venous thrombosis. The mutated allele increased 9.75 fold the risk of venous thrombosis. Moreover, this mutation was the main cause of antithrombin deficiency among patients with venous thrombosis. Finally, we point that this variant can only be detected by molecular methods. All our data support the study of antithrombin Cambridge II in routine thrombophilic tests

Trombosis venosa profunda: consideraciones terapéuticas / Deep venous thrombosis: therapeutic considerations

No disponible

Valoración clínica del empleo preventivo de la antiagregación plaquetaria / Clinical assessment of the preventive use of antiplatelet drugs

No disponible

[The pathology of factor VIII in von Recklinghausen's disease: a new association]. / Patología del factor VIII en la enfermedad de Recklinghausen: una nueva asociación.

A Von Willebrand's disease associated to Von Recklinghausen's disease is described. A an common alteration in the mesenchima is suggested as pathogenic mechanism. DDAVP was used as supportive treatment for bleeding, in preparation for surgery.

Complement in hematological neoplasias.

Total hemolytic complement (CH50) and eight antigenic fractions of the complement system were determined in 30 patients with hematological neoplasias, distributed into the following groups: six cases of non-Hodgkin's lymphomas (NHL), seven cases of chronic lymphocytic leukemia (CLL), five cases of Hodgkin's disease (HD), seven cases of acute leukemia (AL), three cases of chronic myeloid leukemia (CML) and two cases of multiple myeloma (MM). CH50 was titred accordingly to a modification of the Kabat and Mayer method, C1q, C1s, C3, C4, C5, INHC1, C3A and properdin were determined with specific antisera by Manani and Laurell's techniques. The results obtained showed significant increase in CH50 above normal values in patients with HD, AL, and CML, especially the former, even in early stages. C1s was found to be increased in CML and AL, as well as C3 in CML. C4 is increased in CML and HD. C5 follows a course similar to C4, being also increased CLL and MM. C9 is increased in all groups, except NHL. A significant increase in C3A was found in NHL, HD and AL. There were no significant variations in C1s, INHC1 and properdin in any of the former groups. No correlation was found between clinical course and complement increase. The role of complement in neoplastic disease is discussed.