Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia

This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sys-mex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 x 10(9)/L, P<.01), whereas IPF percentage was greater (29.2% vs 3.2%, P<.01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-Fc gamma RIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P=.001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r(2) = -0.578, P=.015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect. (Blood. 2011; 117(21): 5723-5732)