Abstract 3

Inherited thrombocytopenias are an heterogenous group of disorders. Different criteria have been suggested to classify these forms such as inheritance mechanism, platelet volume (MPV), number and morphology of megakaryocytes. We described the clinical, biological, and molecular features of 16 patients of a family with 38 subjects, with an autosomal dominant thrombocytopenia characterized by normocellular bone marrow and normal MPV. TPO serum levels were measured by a quantitative sandwich enzyme immunoassay technique. Platelet aggregation studies was performed directly in the luminaggregometer. Ten subjects with Fanconi's anemia were also analyzed as controls. Linkage analysis was performed between phenotype of the family member versus specific chromosomal regions containing the candidate genes, (chromosome 1 and 3 respectively for c-mpl and TPO). In the thrombocytopenic patients, TPO ranged from 63 to 572 pg/ml; whereas in the unaffected relatives, TPO was from 12 to 93 pg/ml. Ten healthy donors have values similar to those in non-affected family members. In Fanconi's anemia (FA) patients, for instance, the mean value was higher than that observed in thrombocytopenic individuals. These findings show that TPO production seems to be induced by both hypomegakaryocytosis and thrombocytopenia even if the central control appears more relevant. Analysis of the platelet aggregation was normal. Microsatellite markers flanking the TPO and c-mpl genes, gave no evidence for linkage. Further investigations, including the cloning of the gene(s), will provide insights into the molecular pathogenesis of hereditary thrombocytopenias.