Suspects in the tale of lupus-associated thrombocytopenia

Abstract

SummaryImmunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirtyeight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren's syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.

SLE Thrombocytopenia: From Peripheral Platelet Destruction to Central Hemopoietic Defect

“…Although anti-TPO positive patients showed no statistically significant differences in platelet count at specimen collection, longitudinal analysis revealed sustained lower platelet levels and lower circulating levels of TPO [53]. High concentrations of antibodies may bind avidly with natural TPO enabling systemic TPO to be stripped and eliminated by capturing the protein in immune complexes.…”

“…Notably, none of the post-thrombocytopenic individuals exhibited autoantibody activity against platelets. This latter group had received immunosuppressive therapy and achieved normal platelet counts [53].…”

“…Hence, a number of SLE patients produce antibodies that are likely to directly neutralize their own TPO, indicating their bimodal nature: First, by engendering immune-complexes, a non-specific mechanism that enhances peripheral platelet consumption [52,[102][103][104]. Second, by decreasing the effective TPO concentrations for stimulating megakaryopoiesis [53].…”

“…Circulating and platelet-bound anti-PLTs are noted in significant proportion of patients (SLE, AITP) who have active thrombocytopenia. In contrast, when platelets normalize in responders, they become undetectable or decrease significantly and reappear in relapse [44,47,53].…”

Non-Hypersplenism Causes of Peripheral Cytopenias in Patients with Cirrhotic Portal Hypertension: A Review

“…Binding of human anti-platelet autoantibodies to receptors (glycoproteins) on the platelet membrane in any part of the body leads to increased platelet destruction [46,47]. Destruction of platelets may occur in the spleen or in the circulating blood.…”