Assessment of Immature Platelet Fraction in Patients with Ph-Negative Myeloproliferative Disorders and Thrombocytosis.
Authors: Zapletal Ondrej , Blatny Jan , Selingerova Michaela , Jarkovsky Jiri , Penka Miroslav 
Published: October 2019

Abstract
Abstract 4980

Background
Myeloproliferative disorders (MPD) in general result from proliferation of a clone of myeloid cells derived from a neoplastic pluripotent precursor or from connective tissue elements in bone marrow. This leads to increased numbers in one or more blood cell lines in peripheral blood. Some MPDs can be associated with thrombocytosis (MPD-T): essential thrombocythaemia (ET), polycythaemia vera (PV) and early stages of chronic idiopathic myelofibrosis (CIMF). Usually in MPD-T the thrombocytosis is caused by increased platelet production from proliferating mature megakaryocytes, especially in ET. Elevated platelet counts in these patients are often associated with both thromboembolic events and bleeding. One of the goals of MPD treatment is the control of platelet count. Immature platelets mirror the platelet production in bone marrow. In certain automated blood count analyzers it is possible to measure Immature platelet fraction (IPF) from the routine CBC samples sent to haematology lab. Reference range for IPF parameter for method used in this study is 1,1-6,1%.

Objective
Measurement of IPF parameter by fully automated analyzer (XE-2100, Sysmex, Kobe, Japan) in optical channel and analyzing it ( software IPF Master) in patients treated for Ph-negative MPD. We enrolled 85 pts- 67 ET (79%), 10PV(12%) and 8 CIMF (9%) patients; 57 were women and 28 men; median age 56 years ranging from 20 up to 83 years. We analyzed and evaluated IPF in whole group as well as in subgroups depending on diagnosis, gender, age, JAK-2 mutation and platelet count.

Results
At the time of assessment the majority of our pts were already commenced on treatment for their MPD. Platelet counts (plt) in whole cohort ranged from 164 up to 2148 ×109/l, with median 374 ×109/l. Thirty eight pts (45%) had plt < 350 ×109/l. Plt <450 ×109/l (WHO 2008 recommended cut off level for thrombocytosis) were found in 59 pts (69%). IPF median in whole cohort was 5,9% (0,7-14,4%). When comparing IPF in subgroups mentioned above statistically significant differences (p<0,05) was found only between subgroups with normal and abnormal plt counts: IPF median 7,45% (0,8-14,4%) resp. 4,6% (0,7-11,9%), (p=0,002) and between subgroups with less and more than 450×109/l plt (IPF median 6,6% (0,8-14,4%) resp. 3,85% (0,7-9,6%), (p<0,001). Fact, that patients with higher plt had lower IPF and vice versa, was confirmed also by Spearman correlation coefficient. When correlating results of plt a IPF in the whole cohort, we found the trend to indirect dependence (rs= –0,386).

Conclusions
MPD-T patients in our cohort did not have marked elevation of IPF parameter, neither those with high platelet counts (so far untreated pts). Thus we can speculate, that increased number of Plts in peripheral blood is caused by increased number of mature megacaryocytes in bone marrow which produce adequate numbers of platelets without increase of immature fraction rather than increased number of immature platelets released from megacaryocytes appearing in normal numbers in bone marrow Thus it seems that negative feedback of increased Plt counts on releasing of Plts from megacaryocytes is maintained also in patients with MPD-T. Further assessment is needed and should further determine, what is the clinical relevance (if any) of measurement of IPF in patients treated for MPD-T.

Disclosures
Blatny: Sysmex, Czech Republic: Consultancy.