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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2020  |  Volume : 63  |  Issue : 4  |  Page : 593-596
Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India


Department of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India

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Date of Submission04-Jan-2020
Date of Decision07-Apr-2020
Date of Acceptance09-Apr-2020
Date of Web Publication28-Oct-2020
 

   Abstract 


Background: Thrombocytopenia is generally alarming to both clinicians and patients as the consequence can be disastrous. However, some of the conditions associated with thrombocytopenia can be innocuous. Unless this is recognized, detection of thrombocytopenia results in series of further investigations and management plan by clinicians. Hematological investigation in an apparently healthy/asymptomatic individual can throw up many surprises. One of them is thrombocytopenia and giant platelets on peripheral smear examination. Asymptomatic constitutional macrothrombocytopenia (also called as Harris platelet syndrome) is increasingly recognized in north and eastern parts of India. However, this condition is nearly unknown in southern part of our country. With Increased immigrants to south India from northern and eastern states, it becomes imperative for both clinicians and lab physicians to be aware of the magnitude of the condition and interpret appropriately. This can avoid unnecessary anxiety and investigations. Materials and Methods: Blood samples from 300 north and northeastern immigrants (Cases) and equal number of healthy subjects from south India (Controls) were examined for hematological parameters. Peripheral smears were examined for the presence of giant platelets. Results: Constitutional macrothrombocytopenia was seen in 4.3% of the cases and in 0.66% of the controls. The difference was statistically significant with a Fischer exact P value of 0.0067. The prevalence of macrothrombocytopenia on subjective assessment of peripheral smear was 6.7% in the cases and 1% in the control group. Conclusions: The prevalence of Harris platelet syndrome was found to be 4.3% in the immigrants from north and northeastern states.

Keywords: Constitutional macrothrombocytopenia, harris platelet syndrome, mean platelet volume, platelet distribution width

How to cite this article:
Edupuganti HS, Krishnamurthy V. Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India. Indian J Pathol Microbiol 2020;63:593-6

How to cite this URL:
Edupuganti HS, Krishnamurthy V. Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Dec 1];63:593-6. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/593/299300





   Introduction Top


Thrombocytopenia is generally alarming to both clinicians and patients as the consequence can be disastrous. However, some of the conditions associated with thrombocytopenia can be innocuous. Unless this is recognized, detection of thrombocytopenia results in series of further investigations and management plan by clinicians.

Hematological investigation in an apparently healthy/asymptomatic individual can throw up many surprises. One of them is thrombocytopenia and giant platelets on peripheral smear examination. This can be a constitutional condition present since birth and not resulting in any bleeding tendency.

Congenital thrombocytopenia is considered to be a rare group of inherited hematological disorders. It is inclusive of several subgroups, of which inherited giant platelet disorders (IGPDs) is one among the many. It is characterized by decreased platelet count and increased mean platelet volume with variable bleeding manifestations.[1]

Very recently, a group of population from northeastern part of Indian subcontinent were found to have asymptomatic macrothrombocytopenia detected on routine blood investigations in blood donation camps. It was termed as asymptomatic constitutional macrothrombocytopenia or Harris platelet syndrome.[2] Asymptomatic constitutional macrothrombocytopenia is now increasingly reported in north and eastern parts of India. However, this condition is nearly unknown in southern part of our country.

With Increased immigrants to south India from northern and eastern states, it becomes imperative for both clinicians and lab physicians to be aware of the magnitude of the condition and interpret appropriately. This can avoid unnecessary anxiety and investigations. This study was taken up to estimate the prevalence of asymptomatic constitutional macrothrombocytopenia in the immigrants from northern and eastern states of India and compare it with south Indian population.


   Materials and Methods Top


Study design

This was a prospective descriptive study undertaken in the department of pathology. Study was conducted over a period of 18 months from October 2017 to March 2019.

Subjects

Immigrants from north and eastern states of India. All the volunteers who were aged more than 1 year were recruited as cases. Blood donors, volunteers, and school children meeting the inclusion criteria were selected. Blood donors were the major source of samples. Samples obtained from the Master health check facility of our hospital were screened for healthy individuals from south India. They were included as controls.

Sample size

Prior study indicates the prevalence of macrothrombocytopenia to be as 30.3%[3] in northeast Indian population. Assuming a margin of error of 5%, confidence level of 95%, we needed a sample size of 300 and equal number of controls.

Method of collection of data

Two millilitres of venous blood was collected in ethylenediaminetetraacetic acid (EDTA) vacutainer. The blood samples were analyzed in Sysmex XP – 100 (Transaia). Both RBC and platelet indices were recorded. Peripheral smear was stained with Leishman stain and observed for the presence of giant platelets.

A mean platelet volume (MPV) value of >11.5 fl was considered as macro thrombocytes. Platelet count of <1.5 × 109/l was considered as thrombocytopenia. The presence of both of these criteria indicated a positive case. Giant platelet was reported by the pathologist when the size of the platelet was equal to or larger than normal RBC.

Statistical analysis

Medians and interquartile range (IQR) were compared between study groups using Mann– Whitney U test. Chi-square test/Fisher's Exact test was used to compare categorical outcomes between study groups. P value <0.05 was considered statistically significant. Analyse-it version 4.81.6 was used for statistical analysis. Data were also represented using appropriate diagrams like bar diagram, pie diagram, and box plots.

Ethics

Institutional ethics board approved this study with condition of getting informed consent from the volunteers. General consent given by the subjects for blood investigations in the master health checkup sufficed for the controls. Informed consent was obtained from the volunteers.


   Results Top


Males constituted 81.7% of cases and 47.3% of controls. Median age of case was 25 years and 36.5 years in control group. [Table 1] depicts baseline characteristics of the study population. [Table 2] depicts the statewise distribution of cases.
Table 1: Baseline characteristics

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Table 2: State wise distribution of cases

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Of 300, 13 (4.3%) in the case group had macrothrombocytopenia based on MPV and platelet count, while only 2 (0.66%) of 300 had macrothrombocytopenia [Table 3] in the control group. This difference was statistically significant (P = 0.0067).
Table 3: Comparison of incidence of macrothrombocytopaenia between cases and the controls

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The median MPV and platelet distribution width (PDW) were marginally higher in cases in comparison to the controls (10.50 Vs 9.70) and (12.90 Vs 10.60), (P = 0.0001). The median plateletcrit [Table 4] was found to be higher in cases compared to controls (0.270 Vs 0.260) (P = 0.0103).
Table 4: Comparison of platelet indices between cases and controls

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Diagnosis of macrothrombocytopenia based on peripheral smear examination and identification of giant platelets increased the prevalence to 6.7% in cases which was significantly high (P = 0.0001) compared to the controls which was 1% [Table 3].

[Figure 1] illustrates giant platelets in the peripheral smear of both cases and controls.
Figure 1: Giant platelets in the peripheral smear of cases and controls. (Leishman stain, 400×)

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   Discussion Top


Asymptomatic macrothrombocytopenia was once considered rare is increasingly recognized in the recent past. Our study demonstrated the prevalence of asymptomatic macrothrombocytopenia to be 4.3% in the migrant population predominantly from northern and northeastern part of India. The prevalence is quite low in the south Indian population with a rate of 0.06%.

Incidental detection of giant platelets in the peripheral smears of asymptomatic individuals is being reported with increasing frequencies in different population groups throughout the world. Many such reports are also available, from various parts of Indian subcontinent.[4],[5]

Macrothrombocytopenia has been described as one of the categories under inherited giant platelet disorder, which is characterized by decreased platelet count and increased mean platelet volume with variable bleeding manifestations.[1]

Increased reporting of macrothrombocytopenia among the north Indian and northeast Indian population has improved awareness among the healthcare personnel. However, as most of these studies have geographical focus, the awareness of this condition is very poor in the other parts of our country.

With improvement in education, transport system, economy, and wide-open job opportunities, it is very common to find immigrants from various parts of the country. Hence, it is not surprising if an unaware healthcare professional stumble upon this condition to get alarmed and initiate battery of investigations. This results not only in unnecessary procedures but also financial burden on the patients. It is also important to keep in mind the anxiety and concern generated among both patients and clinicians.

Male gender predominated in the case group forming 81.7% of the total. This is because the main bulk of the cases were the volunteers in blood donation camps and the immigrant factory workers. Our findings are in contrast to female predominance noticed in the study population of Parizad et al. who had recruited a total of 10,047 healthy college students from the city of Surat in western India who were investigated for macrothrombocytopenia.[6] Similar study by Chidambaram et al. shows recruiting only males who attended pre-employment check-up.[1] In the study by Naina et al.[7], 154 healthy asymptomatic donors were randomly selected from Tamil Nadu (76) and West Bengal (78) as their study population. The diversity in the study population in different settings makes it difficult to infer about the gender predilection of macrothrombocytopenia. In our study, there was near equal gender distribution in the control group as they were mainly composed of the general population visiting the hospital, seeking general health check-up.

The age ranged from 18 to 59 years with median age of 25 years in the cases and ranged between 18 to 60 years with a median of 36 years in the controls. The difference in the median age between the cases and the controls was statistically significant. Though we intended to match the controls with the cases, the selection settings did not prove conducive for adequate matching. Majority of the cases were young factory workers who had migrated seeking job opportunities, while control samples were collected from the random population visiting the hospital for routine health checkup or with no other specific health ailments.

The state-wise prevalence of macrothrocytopenia in our study is different than that of S Ali et al.[2] who have studied only referred cases. He has reported maximum prevalence in the subjects from West Bengal. The difference in the distribution of macrothrombocytopenia positive cases can be attributed to the objective of this study, to detect prevalence of macrothrombocytopenia from the immigrants of north and northeast Indian states, which depends on the immigrant population.[8]

This study has shown 0.06% macrothrombocytopenia in the control group who were from South India. To the best of our knowledge, there are no studies estimating the prevalence of macrothrombocytopenia in South Indian population.

Another interesting finding in our study was that overall the platelets appear to be big and bulky with high MPV and PDW in north Indian and northeast Indian subjects compared to their south Indian counterparts. This is in concurrence with other studies as well.

Studies by Naina et al.,[7],[9],[10] S. Ali et al.,[8] Denaz Aslan et al.,[11] and Chidambaram Choccalingam et al.[1] have shown that the cases from north Indian states have higher MPV, PDW, low plateletcrit, and decreased platelet count when compared to south Indian population. This leads to a hypothesis that the platelet size varies between different ethnic population. Further large study is needed to test this hypothesis.

Though constitutional macrothrocytopenia is rare in south Indian population, we have reported a prevalence of 0.06%. Thus, we infer that constitutional macrothrombocytopenia is not just limited to any particular region of the country but has widespread distribution throughout the Indian subcontinent.

The importance of having the knowledge of asymptomatic constitutional macrothrombocytopenia is emphasized by the fact that it is commonly misdiagnosed as ITP as it is more common.[12],[13] Some of these cases have undergone invasive procedures such as bone marrow aspiration and splenectomy. There are several reports of patients receiving long term corticosteroids for asymptomatic thrombocytopenias.[4],[14],[15] The index case of our study is an asymptomatic subject who was investigated thoroughly including bone marrow aspiration/biopsy to evaluate the cause of thrombocytopenia. Bone marrow was within normal limits and it was later diagnosed as a case of asymptomatic macrothrombocytopenia.

The study by Noris et al.[13] have shown that platelet size measurement is a powerful diagnostic tool to distinguish ITP from inherited macrothrombocytopenia. They have shown that combining MPV and measurement of Mean Platelet Diameter (MPD) on peripheral smear increases the sensitivity and specificity significantly. However, measurement of MPD was not attempted in this study.

Naveen Kakkar[15] has shown that, analyzers using electrical impedance for evaluating platelets have less ability to detect giant platelets as they underestimate the MPV and platelet count values. In this study, seven additional cases showed giant platelets on peripheral smear examination, apart from the 13 positive cases with thrombocytopenia and MPV of more than 11.5. However, their MPV was less than 11.5 and hence were not counted as the positive cases. Use of Sysmex XP 100, working under the principle of electrical impedance for evaluation of the platelets, might be the reason for the probable slight false lower prevalence (6.3% vs. 4.3%) in this study.


   Conclusions Top


The prevalence of Harris platelet syndrome in the north and northeast immigrants was found to be 4.3% when platelet indices were used for the diagnosis. Highest prevalence was seen in subjects from Rajasthan and Bihar. The prevalence in south India was found to be 0.66%.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Choccalingam C, Samuel P, Swamynathan K. Harris platelet syndrome: The need to recognize the entity. J Med Health Sci 2013;4:11-2.  Back to cited text no. 1
    
2.
Ali S, Ghosh K, Daly ME, Hampshire DJ, Makris M, Ghosh M, et al. Congenital macrothrombocytopenia is a heterogeneous disorder in India. Hemophilia 2016;22:570-82.  Back to cited text no. 2
    
3.
Naina HV, Harris S. Harris platelet syndrome—Underdiagnosed and unrecognized. Arch Pathol Lab Med 2008;132:1546.  Back to cited text no. 3
    
4.
Gohda F, Uchiumi H, Handa H, Matsushima T, Tsukamoto N, Morita K, et al. Identification of inherited macrothrombocytopenias based on mean platelet volume among patients diagnosed with idiopathic thrombocytopenia. Thromb Res 2007;119:741-6.  Back to cited text no. 4
    
5.
Wang G, Wang Z, Liang J, Cao L, Bai X, Ruan C, et al. A phytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis. Acta Haematol 2011;126:95-8.  Back to cited text no. 5
    
6.
Patel P, Shah A, Mishra K, Ghosh K. Prevalence of macrothrombocytopenia in healthy college students in western India. Indian J Hematol Blood Transfus 2019;35:144-8.  Back to cited text no. 6
    
7.
Naina HV, Nair SC, Daniel D, George B, Chandy M. Asymptomatic constitutional macrothrombocytopenia among West Bengal blood donors. Am J Med 2002;112:742-3.  Back to cited text no. 7
    
8.
Ali S, Shetty S, Ghosh K. Bengal macrothrombocytopenia is not totally an innocuous condition. Blood Cells Mol Dis 2016;60:3-6.  Back to cited text no. 8
    
9.
Naina HV, Harris S. Platelet and red blood cell indices in Harris platelet syndrome. Platelets 2010;21:303-6.  Back to cited text no. 9
    
10.
Naina HV, Nair SC, Harris S, Woodfield G, Rees MI. Harris syndrome–A geographic perspective. J Thromb Haemost 2005;3:2581-2.  Back to cited text no. 10
    
11.
Aslan D. Harris platelet syndrome in patients of Non-Indian origin. J Pediatr Hematol Oncol 2016;38:e326-8.  Back to cited text no. 11
    
12.
Miyazaki K, Koike Y, Kunishima S, Ishii R, Danbara M, Horie R, et al. Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia. Hematology 2015;20:587-92.  Back to cited text no. 12
    
13.
Noris P, Klersy C, Zecca M, Arcaini L, Pecci A, Melazzini F, et al. Platelet size distinguishes between inherited macrothrombocytopenias and immune thrombocytopenia. J Thromb Haemost 2009;7:2131-6.  Back to cited text no. 13
    
14.
Balduini CL, Savoia A, Seri M. Inherited thrombocytopenias frequently diagnosed in adults. J Thromb Haemost 2013;11:1006-19.  Back to cited text no. 14
    
15.
Kakkar N, John MJ, Mathew A. Macrothrombocytopenia in north India: Role of automated platelet data in the detection of an under diagnosed entity. Indian J Hematol Blood Transfus 2015;31:61-7.  Back to cited text no. 15
    

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Correspondence Address:
Vani Krishnamurthy
# 70, Prakruthi, BEML 2nd Stage, Rajarajeshwarinagara, Mysuru - 570 022, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_20_20

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