SummaryLabeling of platelets in vivo by 75Se – Selenomethionine (75Se-M) was performed in nine cases of hepatic cirrhosis and thrombocytopenia for evaluation of the kinetics of platelet maturation. Folic acid and vitamin B12 deficiency was excluded by pretreatment of the patients with these agents. The platelet maturation time – time between the injection of the isotope and maximum radioactivity of separated blood platelets – was shortened to 7.7±1.1 days (mean±SD) compared to the normal of 9.1±1.4 days. For explanation a disturbance of megakaryocyte maturation and/or platelet release from the bone marrow is suggested.

In 5 cases of polycythaemia vera and 2 cases with other myeloproliferative disorders accompanied by thrombocythaemia (megakaryocytic myelosis), the megakaryocytes were differentiated and studied by use of the combined application of cytophotometric determination of the DNA content and autoradiography with tritiated thymidine (3H-TdR) in vitro. A shift to the right of the megakaryocyte series, occurence of high polyploidy cells at 64c and a decrease of the 3H-TdR-labeling indices were observed. The data suggest a disturbance of the rhythmical polyploidization of the megakaryocytes, consisting of an elevated proportion of rest cells at the different ploidy stages. The maturation capacity of megakaryocytes may be related more to the resting than to the DNA synthesizing cells.

Labeling of platelets in vivo by 75Se-methionine was performed in premalignant and malignant haematological disorders for evaluation of the kinetics of platelet maturation. The "normal" platelet maturation time (time between the injection of the isotope and maximum radioactivity of separated blood platelets) in eight non-haematological patients showing normal platelet counts was 9.1 days. A shortening of platelet maturation time of 5-7 days was observed in three of four cases with panmyelopathy (high bone marrow cellularity), in three of four cases with malignant lymphatic disorders (multiple myeloma, chronic lymphocytic leukaemia, lymphosarcoma), and in two of four cases with myeloproliferative syndromes. No correlation to the peripheral platelet counts was observed. For explanation of the premature platelet release from the bone marrow a disturbance of the megakaryocyte maturation is suggested.

Proliferation of bone marrow erythroblasts in patients with chronic renal disease was studied by combined application of cytophotometric measurement of the DNA content and 3H-TdR labeling in vitro. A striking decrease of 3H-TdR labeling was found in most of the cases. The proportion of diploid (G0 + G1) as well as of tetraploid unlabeled cells (G2) was increased. The data suggest a disturbed induction of DNA synthesis of resting cells as well as an arrest of cells in G2 being responsable for ineffective cell production in this disease.

In 6 cases initially showing a symptomatology of erythroleukaemia, the proliferation of erythroblasts was studied by combined Feulgen cytophotometry and autoradiography after labelling with ³H-TdR in vivo. A proliferation disturbance was observed consisting of an accumulation of diploid and unlabelled cells and a decreased proportion of cells in S. This defect occurred within the basophilic cell compartment in one case and within the early polychromatic cell compartment in all 6 cases. The results indicate the existence of out-of-cycle cells, which may be responsible for the inefficacy for erythropoiesis in this disease. The defect was present in all 4 cases with acute erythroleukaemia. In one of the two cases showing no deterioration of the physical and haematological condition over a period of years, an additional defect was observed, consisting of a striking accumulation of tetraploid unlabelled cells. Therefore, the technique used may be suitable as a diagnostic tool for evaluation of new types of ineffective erythropoiesis.