Defective megakaryocytopoiesis in the syndrome of thrombocytopenia with absent radii.

The syndrome of thrombocytopenia with absent radii (TAR) is a hereditary condition whose pathogenesis is poorly understood. In this investigation we evaluated a female infant with TAR and her parents using in vitro haematopoietic colony forming assays and an antiserum against platelet membrane glycoproteins (PGP) to label smears of her bone marrow. Megakaryocyte colony growth in vitro was virtually absent in optimally stimulated cultures of the patient's bone marrow progenitors. In contrast, erythroid and myeloid colony growth from the TAR infant's marrow cells was preserved. Staining of the patient's bone marrow smears with PGP antiserum detected no immature, small megakaryocyte precursors. A high level of megakaryocyte colony stimulating activity was detected in serum from the TAR infant, activity comparable to that present in sera from adults with aplastic anaemia. The elevated serum activity decreased by 6 months of age at which time partial platelet recovery had occurred. Evaluation of both peripheral blood haematopoietic progenitor cells and sera from the TAR infant's parents demonstrated no significant abnormalities. We conclude that the principle haematopoietic defect in this patient with TAR syndrome is the absence or arrested development of the committed megakaryocyte progenitor cell. Humoral regulation of megakaryocytopoiesis appears intact and is responsive to the degree of megakaryocytic hypoplasia.