Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology

Thrombocytopenia is a substantial clinical problem for patients with myelod ysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anae mia may further reduce the platelet counts, We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables, S-TPO was also assess ed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients, S-TPO in MDS was not a normally distributed variable : mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml), The controls showed lower S-TPO levels than the patients (median 75 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the hi ghest platelet counts and higher S-TPO levels than the controls (P= 0.005). No association between platelet counts and S-TPO levels was found in the p atients (P = 0.67). TPO levels were generally low in patients with refracto ry anaemia with an excess of blasts (RAEB), but very high levels were found in live patients, Patients with a high transfusion need had higher S-TPO l evels, whereas bone marrow blast counts, cellularity or megakaryocytes allo wed no correlation with S-TPO, Patients with 5q- showed lower TPO levels th an the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF-I-EPO significantly red uced the platelet counts (P = 0.0002), but this change was not related to s ignificant changes in S-TPO levels or morphology, Patients with RARS and th rombocytosis who normalized their platelet counts showed a concomitant redu ction in S-TPO, This may suggest that the increased platelet counts observe d in RARS may be caused by increased S-TPO levels, In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced throm bocytopenia are not usually mirrored by increased S-TPO levels.