Journal List > Korean J Lab Med > v.30(5) > 1011674

Jung, Jeon, Kim, and Kim: Immature Platelet Fraction: Establishment of a Reference Interval and Diagnostic Measure for Thrombocytopenia

Abstract

Background:

Immature platelet fraction (IPF, %) is a measure of reticulated platelets (RPs), which represents the state of thrombopoiesis. The IPF is obtained from an automated hematology analyzer as one of the platelet parameters. This study was performed to establish reference intervals of IPF and its cut-off values for the differential diagnosis of thrombocytopenia.

Methods:

Blood samples from 2,039 healthy individuals (1,161 males, 878 females) were obtained to establish reference intervals. The patient group included patients with idiopathic thrombocytopenic purpura (ITP) (N=150) and aplastic anemia (AA) (N=51) with platelet counts of less than 100×109/L. We evaluated the reliability of the IPF measurements, the reference intervals, and cut-off value for the diagnosis of ITP.

Results:

The reference intervals of IPF were 0.5-3.2% in males and 0.4-3.0% in females (95% confidence interval). The median IPF% of ITP and AA were 7.7% (range, 1.0-33.8%) and 3.5% (range, 0.6-12.9%), respectively. Statistical analysis revealed a significant difference between the IPF% of ITP and AA (P<0.0001). The cut-off value of IPF for differentiating ITP from AA was 7.3% with a sensitivity and specificity of 54.0% and 92.2%, respectively.

Conclusions:

A rapid and inexpensive automated measurement of IPF can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. This study determined the reference intervals of IPF from a large population of healthy individuals, including children. Further studies are needed to establish the clinical utility of IPF.

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Fig. 1.
Optical platelet scattergrams with dot plots coordinated against cell size (forward scatter) and fluorescence intensity (side scatter). Erythrocytes/reticulocytes and mature platelets/immature platelet fraction (IPF) are differentiated by specially designed algorithm of the XE-2100 software. (A) healthy control, (B) immune thrombocytopenia, (C) aplastic anemia.
kjlm-30-451f1.tif
Fig. 2.
Reference interval of immature platelet fraction (IPF) in healthy controls. The IPF values in 2 subgroups of the controls were as follows (median, mean±2 SD, range of 95% confidence interval): (1) males (1.3%, 1.3±0.9%, 0.5-3.2%) and (2) females (1.1%, 1.1±1.0%, 0.4-3.0%), with P<0.0001. The central box represents the values from the lower to upper quartile (25 to 75 percentile). The middle line represents the median. A line extends from the minimum to the maximum value, excluding “outside” and “far out” values. An outside value is defined as a value that is smaller than the lower quartile minus 1.5 times the interquartile range or larger than the upper quartile plus 1.5 times the interquartile range (inner fences). A far out value is defined as a value that is smaller than the lower quartile minus 3 times the interquartile range or larger than the upper quartile plus 3 times the interquartile range (outer fences). These values are plotted with a different marker in red.
kjlm-30-451f2.tif
Fig. 3.
Immature platelet fraction results in healthy controls and thrombocytopenic patients.
Abbreviations: IPF, immature platelet fraction; ITP, immune thrombocytopenia; AA, aplastic anemia.
kjlm-30-451f3.tif
Fig. 4.
The receiver-operating characteristics curves to distinguish the immune thrombocytopenia (ITP) patient group (N=150) from the healthy controls (N=2,039) and aplastic anemia (AA) patient group (N=51). The cut-off value of the immature platelet fraction (2.6%) differentiating ITP from healthy controls is indicated as a circle with a sensitivity of 93.3% and a specificity of 93.9%. The cut-off value for ITP against AA is 7.3% with a sensitivity of 54.0% and a specificity of 92.2%.
kjlm-30-451f4.tif
Table 1.
Subject characteristics
  N (male/female) Median age, year (range) Median PLT, ×109/L (range)
Control (total) 2,039 (1,161/878) 50 (0-87) 234 (150-441)
≤15 yr 30 6 (0-15) 318 (201-440)
>15 yr 2,009 50 (16-87) 233 (150-441)
ITP (total) 150 (60/90) 19 (1-79) 41 (1-99)
≤15 yr 64 7 (1-14) 41 (9-99)
>15 yr 86 42 (16-79) 40 (1-90)
AA (total) 51 (20/31) 41 (5-77) 34 (5-95)
≤15 yr 7 11 (5-15) 41 (13-66)
>15 yr 44 50 (18-77) 34 (5-95)

Abbreviations: PLT, platelet; ITP, immune thrombocytopenia; AA, aplastic anemia.

Table 2.
Reproducibility and stability results of the control and patient group
Range of mean IPF% N Average SD (%) Average CV (%)
Control group 40 0.26 14
<1.0 7 0.15 18
1.0-1.9 22 0.20 14
2.0-2.9 7 0.39 16
≥3.0 4 0.30 8
Patient group 40 1.11 16
4.0-4.9 4 0.53 11
5.0-5.9 14 1.23 20
6.0-6.9 11 1.01 16
≥7.0 11 1.26 13

Abbreviations: IPF, immature platelet fraction.

Table 3.
Reference interval of IPF (%), P<0.0001
  Males Females
N 1,161 878
Mean 1.3 1.1
SD 0.46 0.51
Reference interval    
Mean±2 SD 0.4-2.2 0.1-2.1
2.5-97.5 percentile 0.5-3.2 0.4-3.0
95% CI of lower limit 0.50-0.55 0.38-0.42
95% CI of upper limit 3.05-3.34 2.79-3.13

Abbreviations: CI, confidence interval.

Table 4.
IPF results in healthy controls and patients with thrombocytopenia
Subject N IPF (%) median (range) Platelet count (×109/L) median (range)
Control (total) 2,039 1.2 (0.3-5.9) 234 (150-441)
Boys (≤15 yr) 15 0.7 (0.4-1.5) 293 (221-440)
Girls (≤15 yr) 15 0.7 (0.3-1.3) 326 (201-428)
Men (>15 yr) 1,146 1.3 (0.4-5.7) 225 (150-441)
Women (>15 yr) 863 1.1 (0.3-5.9) 245 (150-429)
ITP (total) 150 7.7 (1.0-33.8) 41 (1-99)
Boys (≤15 yr) 37 8.4 (2.5-26.0) 46 (9-99)
Girls (≤15 yr) 27 5.5 (2.1-22.8) 35 (13-88)
Men (>15 yr) 23 8.2 (1.6-22.5) 37 (15-90)
Women (>15 yr) 63 7.8 (1.0-33.8) 42 (1-90)
AA (total) 51 3.5 (0.6-12.9) 34 (5-95)
Boys (≤15 yr) 2 4.7 (4.2-5.2) 37 (33-41)
Girls (≤15 yr) 5 2.8 (1.8-8.2) 58 (13-66)
Men (>15 yr) 18 4.7 (1.4-12.9) 44 (5-95)
Women (>15 yr) 26 3.5 (0.6-7.5) 30 (6-92)

Abbreviations: IPF, immature platelet fraction; ITP, immune thrombocytopenia; AA, aplastic anemia.

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