Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme‐linked immunosorbent assay

Abstract

Summary.We measured the endogenous plasma concentration of thrombopoietin (TPO) in 76 patients with acquired aplastic anaemia (AA) by a sensitive sandwich enzymelinked immunosorbent assay (ELISA). The plasma TPO concentrations were significantly higher in AA patients when compared to healthy control subjects (P < 0 . 0001) and there was a significant negative correlation between plasma TPO concentrations and platelet counts in 54 AA patients who had not received any platelet transfusions prior to sampling. On the other hand, there was no statistically significant correlation between the TPO concentrations and platelet counts in 22 AA patients who had previously received platelet transfusions.We studied serial changes of plasma TPO concentration in 24 patients who showed an increase in their platelet counts following bone marrow transplantation or immunosuppressive (IS) therapy. Although a decrease in plasma TPO concentration was observed, levels remained above the range of normal healthy controls even in the patients who attained normal platelet counts following therapy. A decrease in TPO concentrations was observed in only half of the responders to IS therapy. Whether exogenous TPO will result in increased platelet counts in AA patients with high TPO levels remains to be determined.

Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes

“…As shown in Figure 1, higher levels of Tpo and G-CSF and lower levels of CD40L, CCL5, CCL11, VEGF, CXCL5, EGF, and CXCL11 were present in AA, compared to healthy controls and to MDS patients. The higher levels of Tpo and G-CSF in AA are consistent with previous observations, [5][6][7][8] likely representing a compensatory physiological mechanism operating to counter impaired blood cell production. Plasma Tpo is strongly linked to the number of megakaryocytes in the bone marrow.…”

“…In vitro, monolayers of marrow-adherent cells, including fibroblasts, endothelial cells, adipocytes, and macrophages, produce a variety of cytokines, which include granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and stem cell factor (SCF), either constitutively or after stimulation with IL-1 or tumor necrosis factor-α (TNF-α). 3,4 To date, measurements of soluble circulating mediating factors in marrow failure have been limited largely to one or two cytokines in AA [5][6][7][8][9] and MDS. 10,11 Because of the complex array of proteins involved in an immune response, the measurement of a single cytokine is likely insufficient to assess alterations in disease.…”

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…Interestingly, Chang et al [22] demonstrated an association between the IFN-γ single nucleotide polymorphism +874 (T/A), which can directly affect the expression of the IFN-γ gene, and response to IST in patients with AA. Thrombopoietin (TPO) levels are markedly increased in AA, and these abnormal levels correlate with disease severity [23]. Elmahdi et al [24] demonstrated significantly higher TPO plasma levels in non-responders to IST than in responders.…”

Age‐related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels

“…The binding to c-Mpl on megakaryocytes/platelets regulates the blood levels of TPO (Kuter & Rosenberg, 1995), and the synthesis of TPO mRNA is constitutive in the liver and kidney (Kaushansky, 1998). Elevation of endogenous TPO values has been observed in disorders with reduced platelet/megakaryocyte mass, including aplastic anaemia (Emmons et al, 1996;Kojima et al, 1997;Marsh et al, 1996) and chemotherapy-induced thrombocytopenia (Chang et al, 1996;Meng et al, 1996;Nichol et al, 1995). Increased TPO levels precede thrombocytosis in an in¯ammatory disorder, Kawasaki disease (Ishiguro et al, 1998), and are caused by decreased expression of c-Mpl in essential thrombocythaemia (Horikawa et al, 1997) and idiopathic myelo®brosis (Moliterno et al, 1998).…”