Effect of recombinant human thrombopoietin on immune thrombocytopenia in pregnancy in a murine model

Abstract

Primary immune thrombocytopenia (ITP) is a serious medical disorder that has the potential for maternal and fetal mortality. Corticosteroids, intravenous immunoglobulin, or both are the first-line treatments for ITP in pregnancy, but choices are limited if patients fail to respond. Recombinant human thrombopoietin (rhTPO) has been proved effective and safe in management of chronic ITP. However, the efficacy and safety of rhTPO for pregnant ITP patients still need to be explored. Here we developed an ideal murine model that simulated human ITP in pregnancy and evaluated the efficacy and safety of rhTPO in management of ITP in pregnancy. Model mice were subcutaneously administered with 0, 150, 1,500 and 15,000 U/kg rhTPO for 14 days. Significant higher platelet counts were noted in rhTPO-treated groups on Day 7, 10 and 14. On Day 20, half the maternal mice were sacrificed. Frequencies of Tregs in CD4+ T cells in rhTPO-treated groups were statistically higher than control. Significant higher plasma levels of TGF-β1 were observed in rhTPO-treated groups than control. There was no significant abnormality in gross or visceral examination of fetuses. The remaining half maternal mice and their pups were observed for at least three weeks to assess vital signs. No abnormal signs were noted.Furthermore, we investigated the underlying mechanisms. Results showed that Tregs were negative for c-Mpl and rhTPO had no direct effect on Tregs. Additionally, the Treg frequency in splenic CD4+ T cells in LY2109761-treated model mice was statistically lower than control. Thus, rhTPO may be a safe and effective option for treatment of pregnant ITP patients.