Evaluation of the immature platelet fraction contribute to the differential diagnosis of hereditary, immune and other acquired thrombocytopenias

Abstract

The differential diagnosis of immune (ITP) and hereditary macrothrombocytopenia (HM) is key to patient management. The immature platelet fraction (IPF) represents the subset of circulating platelets with higher RNA content, and has been shown to distinguish hypo- from hyperproliferative thrombocytopenias. Here we evaluated the diagnostic accuracy of IPF in the differential diagnosis between HM and other thrombocytopenias in a population of patients with post-chemotherapy thrombocytopenia (n = 56), bone marrow failure (n = 22), ITP (n = 105) and HM (n = 27). TPO levels were also measured in HM and ITP matched for platelet counts. Platelet counts were similar in all patient groups. Higher IPF values were observed in both ITP (12.3%; 2.4–65.6%) and HM (29.8%; 4.6–65.9%) compared to hypoproliferative thrombocytopenias. IPF values were also higher in HM compared to ITP, yielding a diagnostic accuracy of 0.80 (95%CI 0.70–0.90; P < 0.0001) to distinguish these two conditions. Intra- and inter-assays reproducibility of IPF in HM patients revealed that this is a stable parameter. In conclusion, IPF is increased in HM compared to both ITP and other thrombocytopenias and contributes to the differentiation between ITP and HM. Further studies are warranted to understand the biological rationale of these findings and to its incorporation in diagnostic algorithms of HM.

Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia

“…Several researchers have improved flow cytometric methods; however, flow cytometry still has various limitations such as being time consuming, difficult sample preparation, requiring a skilled operator, high costs, and lack of quality control [11]. Therefore, Watanabe et al [12] described a fully automated measurement of reticulated platelets, and several studies showed that the automated measurement of immature platelets using the hematology analyzer XE-2100 (Sysmex, Kobe, Japan) is clinically applicable [13][14][15][16][17][18][19][20].…”

Cell surface expression of HLA I molecules as a marker of young platelets

“…Distinguishing these two forms of acquired thrombocytopenia is crucial for diagnosis and for implementation of the appropriate medical treatment. Increased thrombopoiesis leads to a higher proportion of young platelets in peripheral blood . These cells, also called reticulated platelets, are characterized by a greater RNA content …”

“…Currently, the IPF measured by hematology analyzers using dedicated non‐available algorithms is based on an analysis of the blood cells according to their size and their labeling with platelet‐specific and RNA‐specific fluorescent probes . However, this technology presents important limitations since RNA probes also bind nucleotides, which are abundant in platelet‐dense granules.…”

Platelet Counting: Ugly Traps and Good Advice. Proposals from the French-Speaking Cellular Hematology Group (GFHC)

“…IPF increases in diseases when there is increased platelet destruction or consumption and decreases in bone marrow failure. IPF is also correlated with the platelet size and represents an excellent alternative to impedance-derived MPV for detecting hereditary thrombocytopenias with large platelets [27,28]. The highest values of IPF in these hereditary diseases are not related to an increase of RNA content but to the staining of mitochondria and large granules [29].…”