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  • Title: Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP).
    Author: Kapur R, Aslam R, Speck ER, Rebetz JM, Semple JW.
    Journal: Platelets; 2020; 31(3):399-402. PubMed ID: 31146647.
    Abstract:
    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and/or autoreactive T cells destroy platelets and megakaryocytes in the spleen and bone marrow, respectively. Thrombopoietin receptor agonists (TPO-RA e.g. Romiplostim and Eltrombopag) have made a substantial contribution to the treatment of patients with ITP, which are refractory to first-line treatments and approximately 30% demonstrate sustained elevated platelet counts after drug tapering. How TPO-RA induce these sustained responses is not known. We analyzed the efficacy of a murine TPO-RA in a well-established murine model of active ITP. Treatment with TPO-RA (10 ug/kg, based on pilot dose escalation experiments) significantly raised the platelet counts in ITP-mice. Immunomodulation was assessed by measuring serum IgG anti-platelet antibody levels; TPO-RA-treated mice had significantly reduced IgG anti-platelet antibodies despite the increasing platelet counts. These results suggest that TPO-RA is not only an efficacious therapy but also reduces anti-platelet humoral immunity in ITP.
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