Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus

Abstract

Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly understood. In this study, 100 patients with SLE were evaluated for serum thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory parameters such as peripheral blood counts, parameters of blood chemistry and immunologic parameters of SLE. The median platelet count of SLE patients was 230 g/l and 19 were thrombocytopenic (range 8-148 g/l). Thrombopoietin levels in SLE patients were found to be significantly higher than in healthy controls (n = 96; median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE patients, thrombopoietin levels in SLE were still above controls (111 pg/ml, P < 0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation rate and ECLAM score of disease activity, and inversely correlated to complement factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity was found in 23% of SLE patients. Interestingly, these patients had lower platelet counts than SLE patients without anti-thrombopoietin antibodies (median 174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not significantly different. Taken together, thrombopoietin levels are significantly higher in the sera of SLE patients than in healthy controls and anti-thrombopoietin antibodies are frequently found.

Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis

“…TPO did not correlate with disease activity in our SLE cohort, but did correlate with ECLAM scores and ESR levels in the study by Fureder et al 35 This discrepancy may be due to different TPO assays used or the use of SLEDAI versus ECLAM scoring systems, as ECLAM captures a wider variety of symptoms and incorporates ESR. 43 In agreement with the findings by Fureder et al we also demonstrated a negative correlation between C4 levels and TPO.…”

“…Fureder et al described higher median TPO levels in SLE patients than controls (117 vs. 64 pg/ml) and found that TPO was unrelated to platelet counts. 35 In the current study we also observed higher TPO levels in patients with SLE than in controls, although this did not reach statistical significance, but we confirmed the lack of a relation between TPO and concurrent platelet counts or earlier thrombocytopenia. Assuming normal constant production by the liver, TPO levels are determined mainly by uptake and degradation of TPO by megakaryocytes and platelets, and TPO levels in ITP generally correlate poorly with platelet counts due to compensatory increases in megakaryocyte mass.…”

“…43 In agreement with the findings by Fureder et al we also demonstrated a negative correlation between C4 levels and TPO. 35 C4 deposition on platelets has recently been shown to occur in 10-40% of patients with SLE. 44 This intriguing association may reflect an underlying pathway where complement-dependent platelet activation leads to lower platelet mass, with a subsequent rise in TPO.…”

Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies

“…Thrombocytopenia has been linked to autoimmune anti-TPO antibodies in a patient with amegakaryocytic thrombocytopenic purpura [34]. Anti-TPO antibodies were observed in 23% of patients (23/100 studied) with systemic lupus erythematosus and thrombocytopenia, and they were generally observed in the patients with more severe thrombocytopenia [35]. In our study of unselected patients with ITP, however, we identified two patients (1%) with circulating inhibitors of TPO activity, using an assay that measures inhibition of a test cell line that is human TPO and/or murine IL-3 dependent.…”

SLE Thrombocytopenia: From Peripheral Platelet Destruction to Central Hemopoietic Defect

“…Fureder [100] was the first to detect naturally occurring autoantibodies against thrombopoietin (anti-TPO) in 23% of SLE patients and correlate their presence with lower platelet counts, but he failed to display a difference in TPO levels. TPO levels, though high compared to normal controls and consistent with disease activity and complement level, did not correlate with platelet count.…”