Thrombopoietin serum levels in patients with aplastic anaemia: correlation with platelet count and persistent elevation in remission

Abstract

Summary.In an attempt to evaluate the role of thrombopoietin (TPO) in the pathobiology of aplastic anaemia (AA), we have examined TPO levels in sera from 54 AA patients and 119 healthy controls. A total of 92 samples were collected from AA patients: 43 samples were harvested at diagnosis, 23 samples in the cytopenic period after treatment, and 26 samples when patients were in partial (n ¼ 10) or complete remission (n ¼ 16) following immunosuppressive treatment. TPO serum levels were assessed by a sandwich-antibody ELISA that utilized a polyclonal rabbit antiserum for both capture and signal. Serum samples from normal donors revealed a mean TPO level of 95·3 Ϯ 54·0 pg/ ml (standard deviation). Mean TPO levels in AA sera collected at diagnosis and before onset of treatment were 2728 Ϯ 1074 pg/ml (P < 0·001 compared to normal controls; mean platelet count at that time: 27 × 10 9 /l). TPO serum levels of AA patients in partial or complete remission after immunosuppressive treatment were significantly lower than TPO levels at diagnosis (P < 0·001). However, despite normal platelet counts (mean 167 × 10 9 /l), TPO levels remained significantly elevated in complete remission (mean TPO 1009 Ϯ 590 pg/ml, P < 0·001 compared to normal controls). There was a significant inverse correlation between serum TPO levels and platelet counts in AA patients who were not transfused for at least 2 weeks prior to sample collection (coefficient of correlation (r) ¼ ¹0·70, P < 0·0001).In summary, TPO levels were highly elevated in sera of patients with AA. Thus there is no evidence to suggest an impaired TPO response contributing to thrombocytopenia in AA. Thrombopoietin did not return to normal levels in remission, indicating a persisting haemopoietic defect in remission of AA. We hypothesize that elevated levels of TPO may be required to maintain normal or near normal platelet counts in remission of AA.

Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover

“…The plasma TPO level was comparable between SCT recipients with thrombocytopenia and patients with aplastic anemia, a disease characterized by an extremely high level of TPO. 10,11 The frequency of increased TPO was comparable between SCT recipients with thrombocytopenia and patients with aplastic anemia (70 versus 89%). It was noted that eight (30%) SCT recipients lacking thrombocytopenia also had an elevated TPO level.…”

“…6,7 Recently, measurement of the glycocalicin index (GCI) and circulating thrombopoietin (TPO) has been useful for discriminating increased platelet turnover from impaired platelet production. [8][9][10][11][12] Glycocalicin is a fragment cleaved from the extracellular domain of the plateletspecific glycoprotein (GP) Iba, and its plasma level normalized to the platelet count (referred to as the GCI) has been proposed as a useful parameter for evaluating platelet turnover. 13 The GCI is increased in hyperdestructive states, such as in immune thrombocytopenia.…”

High levels of thrombopoietin in sera of patients with essential thrombocythemia: Cause or consequence of abnormal platelet production?

“…Serum thrombopoietin was measured by an enzyme immunoassay as described elsewhere [16,19]. Briefly, a polyclonal antibody directed against a recombinant form of the EPO-like domain was used as capture antibody, and a separate polyclonal antibody to recombinant full-length rHuTPO was coupled to horseradish peroxidase (HRP) and used as the signal antibody (RarHuTPO-HRP).…”

Regulating billions of blood platelets: glycans and beyond

“…[24][25][26][27][28] Circulating TPO levels are elevated in patients with congenital amegakaryocytic thrombocytopenia, caused by germline Mpl mutations, 29,30 thrombocytopeniaabsent radius syndrome, 31 or acquired aplastic anemia. 32,33 In these cases, circulating TPO levels are inversely correlated to platelet counts. Thus, the removal and destruction of TPO released into the bloodstream depends on the platelet and MK mass, and on expression of Mpl on the platelet and MK surface (Figure 2).…”