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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 14  |  Issue : 3  |  Page : 370-374

Importance of platelet indices in the establishment of etiopathological categorization of thrombocytopenia in children


1 Department of Pathology, Dr. B.C. Roy PGIPS, Kolkata, West Bengal, India
2 Department of Anatomy, Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
3 Department of Microbiology, Bankura Sammilani Medical College, Bankura, West Bengal, India

Date of Submission27-Sep-2020
Date of Acceptance05-May-2021
Date of Web Publication30-Sep-2021

Correspondence Address:
Dr. Arijit Majumdar
C/o Sanat Kumar Majumdar, Opposite Duilya Panchayat Office, Charaktala, Mourigram, Andul, Howrah - 711 302, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_331_20

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  Abstract 

BACKGROUND: Evaluation of thrombocytopenia requires thorough clinical history, examination, complete hemogram, including platelet indices and bone marrow study whenever indicated. The etiopathogenetic mechanism decides patient management. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio. The aim of the present study is to evaluate the variation and relationship of platelet indices in hypoproductive and hyperdestructive thrombocytopenia in children.
MATERIALS AND METHODS: A prospective, observational study for a period of 1 year was done on children with thrombocytopenia. Platelet count (PLT), PDW, MPV, and platelet-large cell ratio (PLCR) along with relevant clinical details of the thrombocytopenic patients were collected and tested for the statistical significance by the unpaired t-test.
RESULTS: This study included 80 patients of thrombocytopenia who were classified into hypoproductive (40 cases) and hyperdestructive (40 cases). The mean PLT in hypoproduction group is 49.3 ± 27.8 × 109/l and in hyperdestruction group is 45.7 ± 35.4 × 109/l with a P value of 0.548. The MPV in hypoproduction group is 9.3 ± 0.5 fl and in hyperdestruction group is 12.5 ± 1.7 fl, with a statistically significant P value of 0.002. The mean PDW in hypoproduction group is 16.3 ± 2.3 fl and in hyperdestruction group is 17.7 ± 2.8 fl with a P value of 0.055. The PLCR in hypoproduction group is 27.57% ±3.57% and in hyperdestruction group is 39.65% ±3.53% with a P value of 0.0003.
CONCLUSION: Platelet indices may provide useful information in discriminating the hypoproductive and hyperdestructive thrombocytopenia in children too. Interpretation of platelet indices can help the thrombocytopenic children in the initial management and can avoid invasive investigations.

Keywords: Hyperdestructive thrombocytopenia, hypoproductive thrombocytopenia, platelet indices


How to cite this article:
Majumdar A, Biswas S, Jana A. Importance of platelet indices in the establishment of etiopathological categorization of thrombocytopenia in children. Indian J Health Sci Biomed Res 2021;14:370-4

How to cite this URL:
Majumdar A, Biswas S, Jana A. Importance of platelet indices in the establishment of etiopathological categorization of thrombocytopenia in children. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2021 Dec 7];14:370-4. Available from: https://www.ijournalhs.org/text.asp?2021/14/3/370/327258


  Introduction Top


Thrombocytopenia should be suspected in children with bleeding in mucous membranes or petechiae in the skin, but frequently, its discovery is incidental in a complete blood count (CBC) ordered for other reasons.[1] Normal peripheral blood count of platelets is within the range is 150.0 × 109–450.0 × 109/l and when it goes below 150.0 × 109/l, we call it thrombocytopenia.[2],[3] This same reference range has been used extensively for neonates, regardless of the gestational age or postnatal age.[4] The management of thrombocytopenia is guided by an adequate knowledge of the cause and clinical course of the pathology. The two main mechanisms involved in the pathogenesis of thrombocytopenia are as follows: (a) increased peripheral platelet destruction (hyperdestructive) and (b) a decreased platelet production by the bone marrow (hypoproliferative).[5] Although bone marrow aspiration and biopsy is the gold standard method for evaluating the cause of thrombocytopenia, it is unfortunately, invasive, time-consuming, and needs experts for its interpretation. Previously platelet count (PLT) was the only vital information available about this small blood element. However, recently, automated blood cell analyzers have made it possible to measure various platelet indices, such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) besides a simple CBC and these parameters may provide some valuable information.[6] Very few studies hint that the platelet volume indices are differentially altered in the various causes of thrombocytopenia (hypoproliferative vs destructive).[7],[8] MPV and PDW were found to be higher in patients with immune thrombocytopenic purpura (ITP) than in patients with hypoproductive thrombocytopenia.[7],[9]

Moreover, these studies have been performed mostly on the adult population. Very few studies on the pediatric population are on record. Hence, this study is conducted to establish the relationship between PLT and platelet indices with respect to underlying mechanisms of thrombocytopenia.


  Materials and Methods Top


This was a prospective, observational study carried out at a child hospital for 1 year. The present study started with 100 cases (age group 1–14 years) with thrombocytopenia having PLT <150,000/μl. However, 20 of our thrombocytopenic patients could not be included in our further analysis. They were excluded based on the exclusion criteria of our study.

Inclusion criteria

All patients on whom a bone marrow aspiration was carried out as part of the study of a presentation of thrombocytopenia, considered to be a PLT under 100 × 109/L and who had associated platelet-derived indices from a CBC performed in the institution.

Exclusion criteria

Patients that received medications that altered the production or function of platelets, such as aspirin, chemotherapy, quinine, corticosteroids, etc., were excluded. Furthermore, patients for whom the CBC reading equipment does not provide the results of the platelet-derived indices were excluded.

An Institutional Ethics Committee Clearance was obtained before the start of the study (letter no. BCH/ME/PR/3735 dated: December 15, 2019).

Cases were identified on a daily basis from the hemogram reports generated in the hospital laboratory. For the tests, we drew approximately 2 ml of venous blood from each child through peripheral veins in EDTA vial. Smears are made from peripheral blood and stained by Leishman's stain and examined to confirm thrombocytopenia. Platelet indices collected from automated machine Sysmex XE 2100. The specific parameters included in the study were PLT, MPV, PDW, and platelet-large cell ratio. PLTs along with any special tests performed for determining the etiology of thrombocytopenia such as bone marrow examination, serology for dengue, as clinically indicated, were recorded. Each case was put in either of the two groups hypoproductive and hyperdestructive types based on the etiology of thrombocytopenia. The controls for PLT indices were taken from 80 children of similar age groups with normal CBC and peripheral blood smear. The cases and controls were age adjusted (similar age groups).

Statistical analysis was carried out using the IBM SPSS software package, version 20.0. Quantitative variables were expressed as mean, standard deviation, and analyzed using the Student's unpaired t-test. P < 0.05 was considered statistically significant.

Ethical clearance

An Institutional Ethics Committee Clearance was obtained before the start of the study.[ letter no. BCH/ME/PR/3735 dated: 15.12.2019].


  Results Top


This study included 80 patients with thrombocytopenia, who were classified as follows: Hyperdestructive group (n = 40) and hypoproliferative group (n = 40). Eighty (n = 80) healthy age-matched and sex-matched individuals were selected for the comparison as the control group. The various etiologies in these groups are tabulated in [Table 1].
Table 1: Distribution of cases according to thrombocytopenia categories

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The PLT and volume indices in the control and study participants in our study are tabulated in [Table 2].
Table 2: Mean values of different platelet indices in controls, hyperdestruction thrombocytopenia, and hypoproduction thrombocytopenia

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The statistical comparison of the PLT and volume indices among the various categories of thrombocytopenia is summarized in [Table 3]. P < 0.05 is considered statistically significant.
Table 3: Comparisons of different platelet indices between controls, hyperdestruction thrombocytopenia, and hypoproduction thrombocytopenia

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  Discussion Top


Platelets are essential in primary hemostasis, and it is evident that a low PLT is a significant risk factor for bleeding.[10] Thrombocytopenia is a reduction in the peripheral blood PLT below 150,000/μl. Two main mechanisms involved in the pathogenesis of thrombocytopenia are as follows: (a) increased peripheral platelet destruction (hyperdestructive group) and (b) a decreased platelet production by the bone marrow (hypodestructive group).[5] During evaluation of thrombocytopenic patients, it is essential to identify the etiology, whether it is due to hypoproduction or hyperdestruction which will have impact on the management. Destructive thrombocytopenia category in our study includes idiopathic thrombocytopenia, malaria, kala-azar, and dengue fever, scrub typhus, sepsis, and disseminated intravascular coagulation. The disease categories, which are included in hypoproliferative group, include aplastic anemia (AA), acute leukemias, myelodysplastic syndrome, and Fanconi's syndrome. Bone marrow sampling is invasive and not necessary as the first-line diagnostic procedure in thrombocytopenic cases. It was recommended that it should be reserved for older patients or patients with atypical features (George et al., 1996; Mak et al., 2000; Marsh et al., 2003). Thus, a new noninvasive diagnostic approach for thrombocytopenia is needed. In the search for a new diagnostic approach, we find the platelet indices – MPV, PDW, and platelet-large cell ratio – that can be easily measured in new automatic analyzers. These indices have demonstrated good sensitivity and specificity in the differential diagnosis in the studies of thrombocytopenia in the adult population. However, they have not yet been widely evaluated for the pediatric population.

MPV is a measure of platelet volume, which reflects change in either platelet stimulation or rate of platelet production.[11] Dividing the PCT by the number of platelets (PCT = ratio of platelet volume to whole blood volume) yields the MPV. PDW is a measure of platelet heterogeneity. The heterogeneity in the platelet volume is considered to be due to aging of platelets or due to heterogeneous demarcation of megakaryocytes.[12] Platelet large cell ratio is the measure of larger platelet (0.12 fl in size). It is an established fact that platelet volume indices vary with the PLT.[8]

PLTs did not show any significant differences between the two patient groups in our study. Baig MA has shown in his study that PLTs are less sensitive parameters to differentiate ITP from acute lymphoblastic leukemia (ALL) and AA. Platelet indices showed inverse relationship with PLT as they are increased in hyperdestructive type and linear relationship in hypoproliferative type.[13] Our study showed that hyperdestructive group like ITP patients showed significantly higher MPV results than hypoproductive thrombocytopenic patients (P = 0.002). However, MPV did not show a significant difference between either the hyperdestructive patients or the control group (P = 0.120) or the hypoproductive thrombocytopenia group and the control group (0.553). Similarly, Borkataky et al.[9] found no significant difference in the MPV between the destructive thrombocytopenia groups and the control group.

In our study, we got PDW for control = 14.5 ± 2.21 fl and was 16.3 ± 2.3 fl in hypoproductive and 17.7 ± 2.8 fl in hyperdestructive types. Shah et al.[14] and Borkataky et al.[9] found that the PDW was higher in ITP patients as compared with acute myeloid leukemia patients and nonmegaloblastic hypoproliferative patients, respectively. Kamal et al. in their study showed that alterations in MPV and PDW can give the hematologist an initial hint about the possible mechanism of thrombocytopenia; however, they have limited sensitivity and specificity.[15]

In the present study, the P-LCR was significantly higher in hyperdestructive thrombocytopenic patients as compared with the control group (P = 0.0002) and significantly lower in hypoproductive thrombocytopenia patients compared with the control group (P = 0.0005). Moreover, in our study, the P-LCR was found to be significantly higher in ITP patients compared with hypoproductive thrombocytopenia patients (P = 0.0003). Kaito et al.[6] and Borkataky et al.[9] reported that the P-LCR was increased in destructive thrombocytopenia patients compared with hypoproliferative thrombocytopenia. Aponte-Barrios et al. conducted a similar type of study with platelet indices to promote the use of the automated hemogram report in a more appropriate way and to motivate the awareness of the platelet-derived indices as a source of information for finding the etiology of thrombocytopenia in children.[16]


  Conclusion Top


Our study shows that alterations in platelet volume indices can give the hematologists an initial hint about the possible mechanism of thrombocytopenia. PLTs are less sensitive parameters to differentiate ITP from ALL and AA. PLT indices showed inverse relationship with PLT and can be easily identified during routine hematologic analysis. Thus, platelet indices are important, simple, effortless, and cost-effective tools that should be used and explored extensively, especially in the developing countries, for screening for thrombocytopenia. Some studies also recommended the use of the platelet histogram maximum for the evaluation of thrombocytopenia rather than MPV and PDW to distinguish between ITP and hypoproductive thrombocytopenia.[17] The new analyzer has new platelet-derived parameters including the immature platelet indices or the immature platelet fraction. These should be taken into account in future as possible elements that may contribute to the differential diagnosis of thrombocytopenias in children.[18] Further studies in broader patient groups would enable us to use these newer parameters with greater confidence to offer better patient management. In future, improved research designs and standardized measurements for platelet indices may significantly increase the diagnostic predictive power of platelet indices in the differential diagnosis of thrombocytopenia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Lanzkowsky P. Chapter 12 – Disorders of platelets. In: Lanzkowsky P, editor. Manual of Pediatric Hematology and Oncology. 5th ed. San Diego: Academic Press; 2011. p. 321-77.  Back to cited text no. 1
    
2.
Greer JP, Arber DA, Glader B. Disorders of haemostasis and coagulation. The diagnostic approach to the bleeding disorders. Thrombocytopenia caused by immunological destruction. In: Wintrobe's Clinical Haematology. 10th ed., Part V., Ch. 60., Ch. 62. Philadelphia: Williams and Wilkins; 1998.  Back to cited text no. 2
    
3.
Bessman JD, Gilmer PR, Gardner FH. Use of mean platelet volume improves detection of platelet disorders. Blood Cells 1985;11:127-35.  Back to cited text no. 3
    
4.
Christensen RD. Expected hematologic values for term and preterm neonates. In: Christensen RD, editor. Hematologic Problems of the Neonate. Philadelphia: WB Saunders Co.; 2000. p. 120-2.  Back to cited text no. 4
    
5.
Ntaios G, Papadopoulos A, Chatzinikolaou A, Saouli Z, Karalazou P, Kaiafa G, et al. Increased values of mean platelet volume and platelet size deviation width may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura. Acta Haematol 2008;119:173-7.  Back to cited text no. 5
    
6.
Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: Methodological issues. Platelets 2002;13:301-6.  Back to cited text no. 6
    
7.
Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E, et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in diagnosis of immune thrombocytopenia. Br J Hematol 2005;128:698-702.  Back to cited text no. 7
    
8.
Bessman JD, Williams LJ, Gilmer PR Jr. Platelet size in health and hematologic disease. Am J Clin Pathol 1982;78:150-3.  Back to cited text no. 8
    
9.
Borkataky S, Jain R, Gupta R, Singh S, Krishan G, Gupta K, et al. Role of platelet volume indices in the differential diagnosis of thrombocytopenia: A simple and inexpensive method. Hematology 2009;14:182-6.  Back to cited text no. 9
    
10.
Decousus H, Tapson VF, Bergmann JF, Chong BH, Froehlich JB, Kakkar AK, et al. Factors at admission associated with bleeding risk in medical patients: Findings from the IMPROVE investigators. Chest 2011;139:69-79.  Back to cited text no. 10
    
11.
Bancroft AJ, Abel EW, Mclaren M, Belch JJ. Mean platelet volume is a useful parameter: A reproducible routine method using a modified Coulter thrombocytometer. Platelets 2000;11:379-87.  Back to cited text no. 11
    
12.
Paulus JM. Recent advances in the story of megakaryocyte physiology. Pathol Biol (Paris) 1981;29:133-5.  Back to cited text no. 12
    
13.
Baig MA. Platelet indices: Evaluation of their diagnostic role in pediatric thrombocytopenias (one year study). Int J Res Med Sci 2015;3:2284-9.  Back to cited text no. 13
    
14.
Shah AR, Chaudhari SN, Shah MH. Role of platelet parameters in diagnosing various clinical conditions. Natl J Med Res 2013;3:162-5.  Back to cited text no. 14
    
15.
Kamal MY, El Gendy W, Salama A. Platelet indices as a diagnostic tool in pediatric immune thrombocytopenic purpura. Alex J Pediatr 2018;31:128-31.  Back to cited text no. 15
  [Full text]  
16.
Aponte-Barrios NH, Linares-Ballesteros A, Sarmiento-Urbina IC, Uribe-Botero GI. Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics. Rev Fac Med 2014;62:547-52.  Back to cited text no. 16
    
17.
Niethammer AG, Forman EN. Use of the platelet histogram maximum in evaluating thrombocytopenia. Am J Hematol 1999;60:19-23.  Back to cited text no. 17
    
18.
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. 18
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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