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Platelets. 2019 May 30:1-4. doi: 10.1080/09537104.2019.1624709. [Epub ahead of print]

Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP).

Author information

1
a Department of Experimental Immunohematology , Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.
2
b Keenan Research Center , St. Michael's Hospital , Toronto , ON , Canada.
3
c Division of Hematology and Transfusion Medicine , Lund University , Lund , Sweden.
4
d Department of Pharmacology , University of Toronto , Toronto , ON , Canada.

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.

KEYWORDS:

Immune thrombocytopenia (ITP); immunomodulation; platelet antibodies; platelet counts; thrombopoietin receptor agonist (TPO-RA)

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