Congenital amegakaryocytic thrombocytopenia (CAMT) is a very rare bone marrow failure syndrome presenting with isolated hypomegakaryocytic thrombocytopenia at birth developing into a pancytopenia during the first years of life. Bone marrow transplantation is the only curative therapy for this disease so far. Thrombopoietin (TPO) is the most important hematopoietic growth factor for the regulation of megakaryopoiesis and thrombopoiesis. We investigated TPO production and reactivity in CAMT patients. TPO plasma levels were high like in other forms of thrombocytopenia due to ineffective megakaryopoiesis. However, we found a defective reactivity to TPO: Neither hematopoietic progenitor cells in the bone marrow nor platelets from the peripheral blood did respond to TPO. Flow cytometric investigations demonstrated a lack of expression of the TPO receptor c-Mpl on the surface of platelets. Accordingly, we found mutations in the c-mpl gene, which are predicted to lead to a complete or at least partial loss of function of the TPO receptor. TPO is not only involved in the regulation of megakaryocytopoiesis but also in early hematopoiesis. This seems to be the reason for the general defect in hematopoiesis in CAMT leading to the development of pancytopenia.

Animals↗

PubMedDate not supplied

[Central venous indwelling catheter systems in pediatric oncology from the surgical viewpoint].

A total of 307 central venous access devices were implanted by open surgery in 268 pediatric oncology patients. Their data were retrospectively evaluated from a surgical point of view. The cumulative duration of implantation of 116 subcutaneous tunneled Catheter (STC) was 12,206 days and 45,524 days for 191 portsystems. According to the duration in each group, ports were superior to STC when infection, complication and occlusion were taken into consideration. Infection of the ports was more frequent in children under 3 years than in older patients. Conversely, in the STC-group, children over 10 years presented with the highest rate of infection episodes. The number of complications was high in young children for both types of catheter, decreasing with age. Occlusion rates were similar for both systems and were not age related. However, thrombolysis was more successful in portsystems and few catheters had to be removed for this reason. The age-related data of the presented study are discussed with regard to the surgical procedure. Recommendations are made concerning the adequate choice of catheter system, the surgical technique and postoperative management. Additionally, the medicotechnical aspect of different catheter types is discussed and some suggestions and/or requests are directed to the industrial developing laboratories.

Bacteremia↗

PubMedDate not supplied

[Significance of thrombopoietin and its receptor c-Mpl in regulation of thrombocytopoiesis in thrombocytopenia].

Thrombopoietin (TPO) belongs to the family of hematopoietic growth factors. It supports the growth and differentiation of megakaryocytic progenitors and precursors in vitro and in vivo. The predominant site of production of TPO is the liver. However, regulation of TPO serum levels seems to be not due to transcriptional regulation in the liver but due to degradation of circulating TPO by platelets. Thrombopoietin serum levels in children with thrombocytopenia associated with aplastic anemias, Fanconi anemia and TAR syndrome are elevated whereas in children with idiopathic thrombocytopenia the TPO levels are normal. The defective activation of platelets by TPO in a children with TAR syndrome suggests a defective response of megakaryocytopoiesis to TPO.

Anemia, Aplastic↗