title: 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) × 10(9) /L. In contrast, hypoproliferative thrombocytopenia patients had platelet counts [59 (30-117) × 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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Makar
authors.forename: Olga S
authors.initials: OS
authors.lastname: Zhukov
authors.forename: Mervyn A
authors.initials: MA
authors.lastname: Sahud
authors.forename: David J
authors.initials: DJ
authors.lastname: Kuter
mesh_terms: D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D001565:Benzoates / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D011720:Pyrazoles / Q000627:therapeutic use; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D034061:Thrombopoiesis / Q000187:drug effects; D013926:Thrombopoietin / Q000097:blood* / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag