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Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 347-350
Age-wise reference range of immature platelet fraction in neonates


1 Department of PediatricHaemato-Oncology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
2 Department of Neonatology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India

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Date of Submission10-May-2020
Date of Decision03-Jun-2020
Date of Acceptance27-Jul-2020
Date of Web Publication9-Apr-2021
 

   Abstract 


Immature platelet fraction (IPF) is a quantification of immature platelets in the circulation reflecting the state of thrombopoiesis in the marrow. Normal reference range for IPF has been established in adults. Reference intervals in neonates are highly dependent on gestational age of the neonate. Complete blood counts (CBC) with IPF of all neonates admitted in neonatal intensive care unit (NICU) were analyzed using Mindray BC-6800 Auto Hematology analyzer. Platelet count of less than 150 × 10^9/L was assigned as thrombocytopenia. Neonates were divided into four groups as per the corrected gestational age (CGA) on the day of CBC analysis: 28–32 weeks, 32–34 weeks, 34–37 weeks, and >37 weeks according to World Health Organization (WHO) classification. Mean, standard deviation, and 95% confidence interval for IPF was calculated in each group and reference range for IPF was derived. Mean IPF in neonates with normal platelet count was term––3.58 (95% CI 3.29 to 3.87), late preterm Neonates (34–37 weeks)––4.14 (95% CI 3.82 to 5.0), moderate preterm neonates (32–34 weeks)––4.14 (95% CI 3.46 to 4.82), and in Very Preterm neonates (28–32 weeks)––IPF of 5.51 (95% CI 3.95 to 7.07). We aimed to establish a reference range for IPF in neonates of different gestational age groups. The IPF values in neonates were comparable between hematology analyzers in neonates with normal platelet counts.

Keywords: Gestational age, IPF, neonates, reference ranges

How to cite this article:
Krishnan V P, Golwala Z, Kanvinde P, Patel S, Rao S, Mudaliar S. Age-wise reference range of immature platelet fraction in neonates. Indian J Pathol Microbiol 2021;64:347-50

How to cite this URL:
Krishnan V P, Golwala Z, Kanvinde P, Patel S, Rao S, Mudaliar S. Age-wise reference range of immature platelet fraction in neonates. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 8];64:347-50. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/347/313298





   Introduction Top


Thrombocytopenia is extremely common in the neonatal intensive care unit (NICU) and occurs in up to 18%–35% of admissions.[1] Immature platelet fraction (IPF) is a laboratory quantification of immature platelet in the circulation and represents the measurement of recently released reticulated platelets from the bone marrow reflecting the state of thrombopoiesis in the Marrow.[2],[3],[4] IPF can be reported as either a "%", meaning the percent of platelets that are immature or as an "absolute number" of immature platelets per μL (also known as the immature platelet count or IPC, calculated by multiplying platelet count × IPF%).[4] Normal reference range for IPF has been established in adults in Sysmex and Mindray BC-6800 hematology analyzers and have been found to be in comparable for a subset of patients with normal platelet counts.[5],[6],[7],[8],[9],[10] However, reference intervals in neonates are highly dependent on the gestational and postnatal age of the neonate.[4] Cremer et al.[2] and MacQueen et al.[4] have established reference ranges for IPF in neonates and children <90 days of age respectively using Sysmex XE series Hematology analyzers. However, there are no established Gestational age-wise reference ranges for IPF in neonates, especially preterm neonates.

Hence in this study, we plan to determine the reference values for IPF in newborns of various gestational age with normal platelet counts using Mindray BC-6800 Hematology Analyzer and compare it with the reference ranges in other Hematology analyzers.


   Material and Methods Top


Complete blood counts (CBCs) with IPF of all neonates admitted in NICU in our hospital were analyzed from May to August 2017. Neonates who had received platelet transfusions in the last 5 days were excluded. Mindray BC-6800 Auto hematology analyzer was used. IPF detection was performed using a nucleic acid-specific fluorescent dye (asymmetric cyanine); IPF subpopulation was identified based on size, cellular complexity, and nucleic acid content and then reported on the bidimensional scattergram RET. Because of the retrospective nature of this study, approval of the research ethics committee in our hospital was not required.

Platelet count of less than 150 × 10^9/L was assigned as thrombocytopenia.[9],[11],[12],[13] Thrombocytopenia in all samples was confirmed with peripheral smear examination. Neonates were divided into 4 age groups as per the corrected gestational age (CGA) on the day of CBC analysis––28 to 32 weeks; 32 to 34 weeks, 34 to 37 weeks, and >37 weeks according to WHO classification of preterm.[14] Mean, standard deviation (SD), and 95% confidence intervals (CI) for platelet counts and IPF were calculated in each group. Normal reference range for IPF was derived for each group.


   Results Top


Among the 285 CBCs analyzed from 285 neonates, 50 (17.5%) were found to have thrombocytopenia. There were 121 full-term neonates (>37 weeks), of which 108 (89.2%) had normal platelet count and 13 (10.7%) had thrombocytopenia. Mean IPF in term neonates with normal platelet count was 3.58 (95% CI of 3.29 to 3.87). Among the 13 neonates with thrombocytopenia, the mean IPF was 9.23 (95% CI of 6.62 to 11.84) [Table 1] and [Table 2], [Figure 1] and [Figure 2].
Table 1: Immature platelet fraction in non-thrombocytopenic neonates.

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Table 2: Immature platelet fraction in Thrombocytopenic neona

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Figure 1: Platelet counts and IPF in non-thrombocytopenic neonates

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Figure 2: Platelet counts and IPF in thrombocytopenic neonates

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In late-preterm neonates (34-37 weeks), there were a total of 59 neonates. Forty-Four (74.5%) had normal platelet counts, with a mean IPF of 4.14 (95% CI of 3.82 to 5.0). In this age group, 15 (25.4%) neonates had thrombocytopenia with mean IPF of 13.0 (95% CI of 9.07 to 16.95) [Table 1], [Table 2] and [Figure 1], [Figure 2].

In moderate preterm neonates (32-34 weeks), a total of 51 CBCs were analyzed. Out of the 51 neonates 41 (80.3%) had normal platelet counts, with mean IPF of 4.14 (95% CI of 3.46 to 4.82). Eleven (15.6%) neonates had thrombocytopenia with mean IPF of 11.12 (95% CI of 6.26 to 16.13) [Table 1], [Table 2] and [Figure 1], [Figure 2].

In very preterm neonates (28–32 weeks), there were a total of 42 (75.4%) neonates with normal platelet counts, with mean IPF of 5.51 (95% CI of 3.95 to 7.07). In this age group, 11 (20.7%) neonates had thrombocytopenia with mean IPF of 11.8 with 95% CI of 4.78 to 18.8 [Table 1], [Table 2] and [Figure 1],[Figure 2].


   Discussion Top


IPF is an automated measure of the immature/reticulated platelets in circulation. IPF can be used as a measure of megakaryopoiesis equivalent to reticulocyte count for RBCs. The measurement of reticulated platelets has been used to determine immature platelets in the circulation. This method however is time-consuming and inaccurate.[5] The IPF is an innovative tool to measure young platelets that have recently been released into the circulation.[5],[15] Fully automated measurement of IPF by flow cytometry has been shown to be reliable and reproducible.[16]

IPF is used as a biomarker for predicting mortality in sepsis and has been found to have a better predictive value than other biomarkers in sepsis.[17],[18] Interpreting IPF in neonates involves comparing their measured values with "normal ranges." There have been various studies to establish a normal reference range of IPF in adults using Sysmex and Mindray BC-6800 Hematology analyzers, both of which were found to be comparable in the subset of patients with normal platelet counts.[3],[5],[6],[8],[10] However, studies to establish the reference range in neonates are few.

In our study, we found the mean IPF and 95% CI were higher in neonates as compared with adults and children.[2],[3],[5],[6],[8] These findings are in line with previous studies showing that neonates have a higher proliferation rate of megakaryocytes than adults.[10],[19]

The mean and 95% CI for IPF in our study with Mindray BC-6800 Hematology analyzer were comparable to the reference ranges obtained from the previous studies using Sysmex XE series Hematology analyzers in neonates with normal platelet counts.[2],[4] In our study, the mean and 95% CI for IPF in neonates varied inversely with gestational age with neonates between gestation age between 28 and 32 weeks having the highest values. This is in concordance with the reference interval charts for IPF% in neonates and infants up to 90 days old generated by MacQueen et al.[4] where they had also found the IPF% to be inversely proportional to gestational age up to a gestational age of 32 weeks.

This is to our knowledge, the first attempt made to study normal reference interval of IPF in neonatal population of various gestational ages. The IPF ranges in our study in neonates obtained in Mindray 6800-BC Hematology Analyzer are comparable to those established by MacQueen et al.[4] and Cremer et al.[2] in their cohorts obtained in Sysmex XE Hematology Analyzers.

We realize the limitation of our study. The sample size in our study is smaller as compared to the other studies done to establish normal reference range. The lack of established age-wise reference ranges for normal values of platelets in literature could also be a limitation as it would have hindered direct comparison. We collected values from all the patients admitted in the NICU from the hospital database and did not review the cause of thrombocytopenia manually in each group. In our study, we did not include neonates <28 weeks gestational age due to very small numbers.


   Conclusion Top


We aimed to study and establish a reference range for IPF in neonates of different gestational age groups. The IPF values in neonates were across all gestational age groups higher than the values in adults and children and inversely related to the gestational age of the neonate. The IPF ranges in non-thrombocytopenic neonates is comparable to the reference ranges established previously in other hematology analyzers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kotwal J. Approach to neonatal thrombocytopenia: Immature platelet fraction has a major role. Med J Armed Forces India 2011;67:212-4.  Back to cited text no. 1
    
2.
Cremer M. The immature platelet fraction (IPF) in neonates. In: Diagnostic Perspectives. Vol 1. p. 36-42.  Back to cited text no. 2
    
3.
Sachdev R, Tiwari AK, Goel S, Raina V, Sethi M. Establishing biological reference intervals for novel platelet parameters immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width and their correlations among each other. Indian J Pathol Microbiol 2014;57:231-5.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
MacQueen BC, Christensen RD, Henry E, Romrell AM, Pysher TJ, Bennett ST, et al. The immature platelet fraction: Creating neonatal reference intervals and using these to categorize neonatal thrombocytopenias. J Perinatol 2017;37:834-8.  Back to cited text no. 4
    
5.
Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004;126:93-9.  Back to cited text no. 5
    
6.
Goncalo AP, Barbosa IL, Campilho F, Campos A, Mendes C. Predictive value of immature reticulocyte and platelet fractions in hematopoietic recovery of allograft patients. Transplant Proc 2011;43:241-3.  Back to cited text no. 6
    
7.
Yamaoka G, Kubota Y, Nomura T, Inage T, Arai T, Kitanaka A, et al. The immature platelet fraction is a useful marker for predicting the timing of platelet recovery in patients with cancer after chemotherapy and hematopoietic stem cell transplantation. Int J Lab Hematol 2010;32:e208-16.  Back to cited text no. 7
    
8.
Ko YJ, Kim H, Hur M, Choi SG, Moon HW, Yun YM, et al. Establishment of reference interval for immature platelet fraction. Int J Lab Hematol 2013;35:528-33.  Back to cited text no. 8
    
9.
Roberts I, Murray NA. Neonatal thrombocytopenia: Causes and management. Arch Dis Child Fetal Neonatal Ed 2003;88 359-64.  Back to cited text no. 9
    
10.
Pecoraro A, Troia A, Sacco M, Maggio A, Di Marzo R, Gioia M. Evaluation of IPF counting on Mindray BC-6800 hematology analyzer. Int J Lab Hematol 2016;38:e89-92.  Back to cited text no. 10
    
11.
Pahal GS, Jauniaux E, Kinnon C, Thrasher AJ, Rodeck CH. Normal development of human fetal hematopoiesis between eight and seventeen weeks' gestation. Am J Obstet Gynecol 2000;183:1029-34.  Back to cited text no. 11
    
12.
Forestier F, Daffos F, Catherine N, Renard M, Andreux JP. Developmental hematopoiesis in normal human fetal blood. Blood 1991;77:2360-3.  Back to cited text no. 12
    
13.
Forestier F, Daffos F, Galacteros F. Haematological values of 163 normal fetuses between 18 and 30 weeks of gestation. Pediatr Res 1986;20:342-6.  Back to cited text no. 13
    
14.
Howson CP, Kinney MV, McDougall L, Lawn J. Born Toon soon: Preterm birth matters. Reprod Health 2013;10:S1.  Back to cited text no. 14
    
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Piva E, Brugnara C, Chiandetti L, Plebani M. Automated reticulocyte counting: State of the art and clinical applications in the evaluation of erythropoiesis. Clin Chem Lab Med 2010;48:1369-80.  Back to cited text no. 15
    
16.
Ruisi MM, Psaila B, Ward MJ, Villarica G, Bussel JB. Stability of measurement of the immature platelet fraction. Am J Hematol 2010;85:622-4.  Back to cited text no. 16
    
17.
Cremer M, Weimann A, Szekessy D, Hammer H, Buhrer C, Dame C. Low immature platelet fraction suggests decreased megakaryopoiesis in neonates with sepsis or necrotizing enterocolitis. J Perinatol 2013;33:622-6.  Back to cited text no. 17
    
18.
Koyama K, Katayama S, Muronoi T, Tonai K, Goto Y, Koinuma T, et al. Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis. PLoS One 2018;13:e0192064.  Back to cited text no. 18
    
19.
Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res 1998;43:148-51.  Back to cited text no. 19
    

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Correspondence Address:
V P Krishnan
Department of Pediatric Haemato-Oncology, Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_501_20

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