Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosis

Abstract

Reticulated platelets are RNA-rich immature platelets and are thought to reflect the ability of bone marrow to produce platelets (1). Reticulated platelets can be measured by flow cytometry using thiazole orange (2). However , the measurement of the reticulated platelets has not been included in routine examinations because of the complexity of the procedure. Furthermore, the standard method for measurement of reticulated platelets has not been established so far. Some assays use whole blood and others use platelet-rich plasma. Monoclonal antibod-ies specific to platelets used to delineate reticulated plate-lets are varying and normal counts of reticulated platelets are reported to vary from 1% to 20% (2-16). A recent software program using the Sysmex XE2100 fully automated complete blood count analyzer (Sysmex, Kobe, Japan) has facilitated the measurement of RNA-rich immature platelets automatically. Although this instant assay lacks specificity, the measurement of the immature platelet fraction percentage in total platelets (IPF%) may be useful in ascertaining whether thrombo-cytopenia is caused by reduced platelet production or increased metabolic turnover because of platelet destruction. Indeed, IPF% has been successfully utilized to differentiate ITP and aplastic anemia (AA) (17). The measurement of IPF% has also been shown to be useful in predicting platelet recovery following Abstract Objectives: Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. Method: Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. Results: IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 · 10 9 ⁄ L (median, 71 · 10 9 ⁄ L), respectively. Twelve patients showed platelet counts more than 50 · 10 9 ⁄ L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. Conclusions: These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities.

Immature Platelet Fraction: Establishment of a Reference Interval and Diagnostic Measure for Thrombocytopenia

“…The previously reported reference interval using the Sysmex XE-2100 for healthy adults is between 0.4% and 10% [1,9,[22][23][24][25][26][27]. The limitations of these reported reference intervals are: 1) small control groups, including less than 150 individuals, 2) incorrect application or lack of application of the CLSI guideline for determining reference intervals, and 3) exclusion of pediatric individuals in the control group.…”

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

“…explained by an increased turnover of platelets produced by abnormal megakaryocytes. 28 We previously demonstrated that the aberrant increase in the proportion of immature platelets is frequently seen in MDS patients with chromosomal abnormalities associated with poor prognosis. 28 Increased production and destruction of platelets may accelerate TPO consumption in patients with RAEB, leading to a decrease in plasma TPO levels.…”

“…28 We previously demonstrated that the aberrant increase in the proportion of immature platelets is frequently seen in MDS patients with chromosomal abnormalities associated with poor prognosis. 28 Increased production and destruction of platelets may accelerate TPO consumption in patients with RAEB, leading to a decrease in plasma TPO levels. Although one report demonstrated increased TPO receptors on the megakaryocytes of MDS patients using flow cytometry, 14 we were unable to reproduce their results (data not shown).…”

Correlation between immature platelet fraction and reticulated platelets. Usefulness in the etiology diagnosis of thrombocytopenia

“…A recent paper communicates about the potential usefulness as a marker of progression to cirrhosis in patients with chronic liver disease (26). It has been postulated also the value of the determination of IPF in the myelodysplastic syndrome, where IPF rates > 10% would be associated with a greater number of karyotypic abnormalities (including abnormalities of chromosome 7), thus conferring a worse prognosis in myelodysplastic syndromes (27, 28).…”

“…, thus conferring a worse prognosis in myelodysplastic syndromes (27,28). IPF is an automated technique for RP determination, standardized, reproducible and it is a methodology that saves time, so it could be a useful screening technique in patients with isolated thrombocytopenia to discriminating peripheral platelet destruction from other causes of thrombocytopenia.…”