Serum Thrombopoietin (TPO) Levels in Patients with Amegakaryocytic Thrombocytopenia Are much Higher than those with Immune Thrombocytopenic Purpura

Abstract

SummaryWe assayed serum thrombopoietin (TPO) levels in amegakaryocytic thrombocytopenia (AMT) and immune thrombocytopenic purpura (ITP) patients by using a newly established enzyme-linked immunosorbent assay (ELISA). TPO levels in AMT patients were quite high (mean ± SD = 13.7 ± 11.2 fmoles/ml, n = 4), whereas those in ITP patients were only slightly higher (1.25 ± 0.39, n = 12) than those of the healthy donors (0.55 ± 0.2, n = 20). Furthermore, in ITP patients no correlation was observed between platelet counts and serum TPO levels (correlation coefficient = 0.14). We further assayed serum TPO levels sequentially during steroid treatment in patients with AMT and ITP. In one AMT patient serum TPO levels started to decrease in accordance with the increase of megakaryocyte counts, which preceded the increase in platelet counts. However, in ITP patients serum TPO levels did not change significantly throughout the course of the treatment despite the recovery of platelet counts. Based on these findings, we conclude that serum TPO levels may be regulated at least in part by megakaryocyte counts.

The molecular and cellular biology of thrombopoietin: the primary regulator of platelet production

“…However, the use of TPO in these patients conceivably might also stimulate proliferation of the neoplastic blast population, because of the frequent expression of Mpl (Hashimoto et al, 2000;Wetzler et al, 1997). In the case of immune thrombocytopenia (ITP), TPO levels are only mildly elevated due to the increased megakaryocyte mass in the bone marrow (Kosugi et al, 1996;Mukai et al, 1996).…”

Incomplete restoration of Mpl expression in the mpl−/− mouse produces partial correction of the stem cell–repopulating defect and paradoxical thrombocytosis

“…Furthermore, because TPO is internalized and destroyed after binding to Mpl, plasma TPO levels are primarily regulated by megakaryocyte and platelet mass. [13][14][15][16][17][18][19][20] In murine hematopoietic stem cell gene transfer studies, ectopic expression of an Mpl transgene under the direction of a constitutive promoter produced dyshematopoieses with both inappropriate expansion of erythroid cells and the development of thrombocytopenia due to depressed plasma TPO levels. [21][22][23][24] Successful gene therapy of CAMT necessitates ectopic expression of Mpl in a manner that faithfully mimics its pattern in nature.…”

Allogeneic stem cell transplantation for patients with congenital amegakaryocytic thrombocytopenia (CAT)

“…1 While the exact underlying defect of this disorder is not well understood, the problem seems to be due to an intrinsic stem cell defect rather than an abnormality of the bone marrow microenvironment or an inhibitory factor in the patients' plasma. 7 High levels of thrombopoietin (TPO) have been found in the sera of affected patients; 8,9 TPO is the main regulator of megakaryopoiesis. 10 More recently, a lack of TPO reactivity of platelets and hematopoietic progenitors from patients with CAT has been described.…”