Thrombopoietin levels in patients with disorders of platelet production: Diagnostic potential and utility in predicting response to TPO Receptor agonists

Abstract

Thrombopoietin (TPO) is the major regulator of megakaryopoiesis. Measurement of serum TPO levels may help distinguish between various causes of thrombocytopenia and predict treatment response to TPO receptor agonists. Serum TPO levels from 118 healthy volunteers and 88 patients with abnormal platelet counts were measured using a quantitative ELISA assay. The mean (range) TPO level in healthy volunteers was 39 (7-99) pg/mL. TPO values were correlated with the patient's diagnosis, platelet count, and response to TPO receptor agonists. 88 patients with history of consumptive thrombocytopenia (39) or hypoproliferative thrombocytopenia (49) were analyzed. Median (interquartile range) TPO level for consumptive thrombocytopenia patients was 63 (48-98) pg/mL with a corresponding median (interquartile range) platelet count of 73 (28-146) 3 10 9 /L. In contrast, hypoproliferative thrombocytopenia patients had platelet counts [59 (30-117) 3 10 9 /L] comparable with consumptive thrombocytopenia patients, but significantly higher serum TPO levels [706 (358-1546) pg/mL, P < 0.0001]. Analysis of 21 ITP patients treated with TPO receptor agonists demonstrated that a TPO level >95 pg/mL was associated with lack of clinical response (P < 0.002). TPO levels may have diagnostic utility in discriminating between patients with hypoproliferative and consumptive thrombocytopenia. Elevated TPO levels in ITP patients may predict a poor clinical response to treatment with TPO receptor agonists. Am. J. Heamtol. 88:1041Heamtol. 88: -1044Heamtol. 88: , 2013. V C 2013 Wiley Periodicals, Inc. IntroductionThrombopoietin (TPO) is the major regulator of platelet production. Prior studies in animal models [1-3] and humans [4] have demonstrated that TPO levels vary inversely with circulating platelet mass. Additional clinical studies have suggested that TPO levels also vary inversely with the rate of megakaryopoiesis [5][6][7][8][9][10]. Thus, TPO levels may help distinguish between the various disorders of thrombocytopenia, with elevated TPO levels associated with hypoproliferative thrombocytopenia (e.g., aplastic anemia) but normal TPO levels associated with consumptive thrombocytopenia (e.g., immune thrombocytopenia) [5][6][7][8]10]. In addition, the introduction of TPO receptor agonists for the treatment of thrombocytopenia has created an interest in predicting the response of patients to these agents [11]; TPO levels may help predict treatment responses.To assess the performance characteristics of a TPO assay in a clinical setting, we measured the serum TPO concentration in a panel of healthy humans as well as patients with diverse hematologic diseases. We then correlated the TPO level with platelet count, diagnosis, and treatment response. Our goals were (1) to determine the normal range of TPO levels, (2) to determine whether TPO levels could help discriminate between different disorders of platelet production, and (3) determine whether TPO levels might help predict the platelet response in those patients treated with a TPO receptor agonist ...

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

“…While the utility of TPO levels for an ITP diagnosis is uncertain, a potential prognostic relevance has been identified. Patients with relatively high TPO, defined as >95 pg/mL, were found to have only transient or partial responses to TPO mimetic therapy . Assays to measure canine TPO are not currently available.…”

Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI

“…-The 2 TRAs, eltrombopag and romiplostim, are not cross-resistant, i.e., if one TRA fails, the other one can still achieve a response [90,91]. -Romiplostim seems to be less effective when the serum thrombopoietin levels are high [92]. -With TRAs, about half of the patients can discontinue all other ITP drugs (e.g., steroids).…”

Effect of Combretum molle (Combretaceae) seed extract on hematological and biochemical parameters

“…Damaged liver and kidney might increase release of this hormone to the blood and increases production of platelets. This was evidenced by the renal or liver failure conditions associated with the increased platelet production in patients with kidney and liver problems (Linthorst et al, 2002;Makar et al, 2013). This is because of high level of thrombopoietin in blood of patients which causes abnormal production of platelets (Makar et al, 2013).…”