Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia.

Fourteen children with congenital thrombocytopenia were analysed in order to unravel the mechanisms underlying their thrombocytopenia and to evaluate the value of new laboratory tests, namely measurement of plasma thrombopoietin (Tpo) and glycocalicin (GC) levels and analysis of megakaryocytopoiesis in vitro . Three groups of patients were included. The first group (n = 6) was diagnosed with congenital amegakaryocytic thrombocytopenia. They had no megakaryocytes in the bone marrow, three out of four patients showed no megakaryocyte formation in vitro , and all had high Tpo and low GC levels. Mutations in the thrombopoietin receptor gene, c-mpl , were the cause. The second group of patients (n = 3) had normal Tpo and severely decreased GC levels. In bone marrow, normal to increased numbers of atypical, dysmature megakaryocytes were present. In vitro megakaryocyte formation was quantitatively normal. A defect in final megakaryocyte maturation and subsequent (pro-)platelets may be the cause of the thrombocytopenia. The patients in the third group (n = 5) had Wiskott-Aldrich syndrome (WAS). They had normal Tpo and GC levels and normal megakaryocyte formation both in vivo and in vitro . This corresponded with the generally accepted hypothesis that thrombocytopenia in WAS is due to increased platelet turnover. In conclusion, different causes of congenital thrombocytopenia can be distinguished using three parameters: Tpo and GC plasma levels and in vitro analysis of megakaryocytopoiesis. Therefore, these parameters may be helpful in early diagnosis of different forms of congenital thrombocytopenia.