Significance of platelet parameters in cases of iron deficiency anemia with reference to thromboembolic complications - A study in central India Deshmukh AV, Konsam V, Gupta A, Gangane NM

ORIGINAL ARTICLE

Year : 2021 | Volume : 10 | Issue : 3 | Page : 165-169

Significance of platelet parameters in cases of iron deficiency anemia with reference to thromboembolic complications - A study in central India

Abhay Vilas Deshmukh¹, Vaskarjeet Konsam², Anupama Gupta¹, Nitin M Gangane¹
¹ Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India
² Department of Pathology, Shija Hospital and Research Institute, Imphal West, Manipur, India

Date of Submission	09-Sep-2021
Date of Acceptance	05-Nov-2021
Date of Web Publication	6-Dec-2021

Correspondence Address:
Anupama Gupta
Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha - 442 102, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/sjhs.sjhs_132_21

Abstract

Background: Iron deficiency anemia (IDA) is one of the most common and potentially treatable health problems. The platelet behavior is often unpredictable and complicated in IDA. The present study was aimed to evaluate significance of platelet parameters in IDA, effect of iron therapy on them, and complications related to platelet parameters in such cases. Patients and Methods: It was a prospective observational study. A total of 85 outdoor and indoor consecutive patients of pure IDA with low ferritin levels were enrolled as cases. Platelet parameters – mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (Pct) obtained by automated blood cell counter were studied at the time of presentation and after 1 month of oral iron therapy. Results: IDA was diagnosed more in females (65, 76.5%). All the basic hematological parameters were significantly altered in cases (P < 0.005) except WBC and Pct. Red blood cell parameters have a linear relationship with MPV and inverse with platelet count and PDW. 35 out of 85 IDA cases (41%) showed reactive thrombocytosis (RT). Mild RT was significantly associated with mild anemia (8.1–10 gm%; n = 11) as compared to moderate RT. Six thromboembolic complications were encountered which presented mostly with mild RT, less MPV, high PDW and Pct linearly increasing with platelet count. On follow-up, cases with RT after 1 month of oral iron therapy, platelets showed significant reduction (P = 0.00015) and rise in Hb levels (P = 0.025). Conclusions: RT is common finding in IDA. Thromboembolic central nervous system complications should always be kept in mind because they may deteriorate the clinical picture in otherwise benign course of IDA.

Keywords: Iron deficiency anemia, platelet parameters, reactive thrombocytosis, thromboembolic complications

How to cite this article:
Deshmukh AV, Konsam V, Gupta A, Gangane NM. Significance of platelet parameters in cases of iron deficiency anemia with reference to thromboembolic complications - A study in central India. Saudi J Health Sci 2021;10:165-9

How to cite this URL:
Deshmukh AV, Konsam V, Gupta A, Gangane NM. Significance of platelet parameters in cases of iron deficiency anemia with reference to thromboembolic complications - A study in central India. Saudi J Health Sci [serial online] 2021 [cited 2023 Jun 9];10:165-9. Available from: https://www.saudijhealthsci.org/text.asp?2021/10/3/165/331770

Introduction

Iron deficiency is one of the world's most common and potentially treatable health problems. Several changes in platelet behavior have been reported in iron deficiency anemia (IDA).^[1] Moderate IDA usually shows reactive thrombocytosis (RT) while thrombocytopenia is usually found in severe IDA suggesting a biphasic mechanism. After iron therapy, both thrombocytosis and thrombocytopenia may disappear.^[2],[3] Iron is postulated to play a key role in the synthesis of platelets and in the regulation of thrombopoiesis.^[4] However, exact mechanism leading to these pathological changes is not known exactly.^[5] IDA is also reported to be associated with complications such as fatal cerebrovascular thrombosis, central retinal vein thrombosis, further suggesting a strong relationship between thrombopoiesis and iron metabolism.^[6]

Recent studies have shown lower mean platelet volume (MPV) and higher platelet distribution width (PDW) values in cases of complications in IDA. As new platelets are metabolically and enzymatically more active having a great prothrombotic potential, these parameters are recommended to be used as alternative markers for platelet activity.^[7] The relationship between different platelet parameters such as MPV, PDW, and risk of complications of thrombosis in IDA gained attention of researchers.^[8] However, there are very few reports in literature on significance of platelet profile in IDA, especially in Central India. This study tried to explore the effects of iron deficiency on different platelet parameters with reference to thrombotic complications in IDA.

Patients and Methods

Case selection

The present study was a prospective observational study conducted in Department of Pathology at Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, a rural tertiary care hospital in Central India over the period of 24 months after clearance from Ethics committee of the Institute. One hundred and twelve consecutive cases of first time diagnosed IDA registered in the Clinical Pathology laboratory or Hematology section of Department of Pathology were selected. Hemoglobin level 10 gm% or less with microcytic hypochromic red blood cells (RBCs) was the initial selection criteria. IDA was then confirmed by clinical history of the patient, relevant physical examination, and serum ferritin; irrespective of age and sex. Serum ferritin value of 15 ng/ml was considered as cut off point for iron-deficient state.^[9] Thrombocytosis was defined as platelet count more than 400 × 10⁹/l^[7] while thrombocytopenia was defined by platelet count <150 × 10⁹/l. A bedside bleeding time, clotting time, coagulation screening, and blood gas analysis were also done if the patient presented with a thromboembolic phenomenon or if there were any signs or symptoms of bleeding tendencies or if there is any alteration in the platelet count, either thrombocytosis or thrombocytopenia. Furthermore, a complete thrombophilia work up for both acquired (which included myeloproliferative neoplasm and paroxysmal nocturnal hemoglobinuria) and inherited risk factors for thrombosis cases were done in these cases. Twenty-seven cases were excluded later owing to associated clinical disorders which may also affect platelet parameters such as hematologic disorders other than IDA, chronic heart disease, chronic kidney disease, or antiplatelet drugs; to finally have 85 patients as study cases. In these 85 study cases, platelet count and platelet volume indices (MPV, PDW), plateletcrit (Pct) at presentation and after 1 month of oral iron therapy were studied along with correlation of these parameters with the presence or absence of hemostatic disorders.

Control cases

Same number of cases (n = 85) with normal Hb level registered in Clinical Pathology Outpatient Department were taken as control cases.

Ethics

The study protocol was approved by the Institute Ethics committee before conducting the study. Patient confidentiality was maintained during all research procedures.

Statistical analysis

Data were recorded and analyzed using Microsoft Excel and software used in the analysis was SPSS22.0 (IBM Corp. Released 2015. IBM Statistics for Windows, Version 20.0: Armonk, New York, United States) and graph pad PRISM 6.0 version. Continuous variables were expressed as means ± standard deviation. Categorical variables were expressed in terms of number and percent. Paired and unpaired t-test for relationship between platelet parameters and other hematological parameters was done. P < 0.05 was considered to be statistically significant.

Results

Basic demography of study cases showed 65 females and 20 males. Most common group with IDA were adult (20–50 years) females in childbearing age (76.5%). Males were also affected mostly in this age group only [Figure 1].

Figure 1: Number of study cases according to age and sex

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Hematological parameters were significantly altered in study cases when compared to control cases. Mean RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and MPV were significantly less in study cases while changes in mean WBC count were not significant. All platelet parameters except Pct showed significant difference in study and control group. Platelet count and PDW were significantly increased in IDA while MPV showed a remarkable decrease [Table 1].

Table 1: Overall hematological picture in study and control cases

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Platelet count was increased in 41% of study cases (35/85). Thrombocytosis was consistently associated with all grades of anemia although the percentage of thrombocytosis cases decreased gradually with severity of anemia. The percentage of cases showing thrombocytosis was 68.7% (11/16 cases) for Hb 8.1–10 gm%, 44.4% (12/27 cases) for 6.1–8 gm%, 43.4% (10/23 cases) for 4.1–6 gm%, and only 11% (2/18 cases) for Hb <4 gm%. Moderate thrombocytosis was seen in 4–8 gm% Hb group. Thrombocytopenia is not reported in any of our study cases [Table 2].

Table 2: Correlation of hemoglobin (g %) and platelet counts

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6 patients presented with thromboembolic complications including 5 cases of central nervous system and one case of cardiac involvement. These complications did not spare any age group and sex (3 children and 3 adults; 4 female and 2 male patients). Platelet count was reported to be in mild RT range in most (4 cases) of them but we also recorded normal count (toward upper limit) in one case and moderate RT in another. MPV was less than normal in 3 cases with minimum increase in platelet count and toward higher normal limit in other 3 with more increase in platelet count. Pct showed a linear relation to platelet count and PDW was higher than normal in 3 cases [Table 3]. Thus, platelet parameters failed to show any consistent quantitative disorder in these cases. Prothrombin time and activated partial thromboplastin time were within normal range in all 6 cases. Total 35 patients turned up for follow-up after 1 month of oral iron therapy. Out of these, 25 patients initially presented with normal platelet counts and rest 10 presented with mild thrombocytosis. No case presenting with moderate RT turned up for follow-up unfortunately. Follow-up hemograms reported improvement in hemoglobin level with simultaneous normalization of all platelet parameters including count, MPV, and PDW.

Table 3: Hematological parameters in cases of thromboembolic complications associated with iron deficiency anemia

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Discussion

In general, IDA is more common in females worldwide^[10],[11] so is the finding of the present study. However, iron deficiency is prevalent in Indian males also (55%–88% in different states in National family health survey III, quoted by Yadav el al.^[12]). In fact, we found that males were more affected than the females in children <10 years of age (60% males in this study). Although ascertaining the overall prevalence of IDA in the study area is not possible by the present study design, we included only pure IDA cases.

All platelet parameters except Pct showed significant difference between the study and control group. Similar findings are observed in literature by Chetan et al.,^[1] Sarangi et al.,^[13] and Gupta et al.^[14] Similar to the present study, Han et al.^[15] also found that increased platelet count in IDA was decreased or returned to normal after treatment. Furthermore, MPV tends to increase on iron therapy according to Yuce et al.^[16]

There is a wide variation in the percentage of thrombocytosis associated with IDA in the medical literature. Various studies report 13.3%–65% adult IDA cases showing RT (Chetan et al.,^[1] Kadikoylu et al.,^[4] Gupta et al.,^[14] Kuku et al.,^[17] Chandna et al.^[18]). In children, thrombocytosis is reported in 10% by Syed et al.^[19] Sarangi et al.^[13] in their study found the most common cause of secondary thrombocytosis as infection (39.5%) alone followed by IDA (14.1%). In his study, they noted a decrease in MPV, platelet large cell ratio and PDW with increasing platelet count was statistically significant (P < 0.05). In the present study, we have taken patients of all ages and both sexes and our percentage of cases with thrombocytosis lies well within the reported range. The increase in platelet count may be secondary to an increased thrombopoietic substance, general activation of bone marrow in anemia, a low level of circulating hemoglobin, a low level of serum or tissue iron, or a combination of these factors.^[20] Although erythropoietin (Epo) is the primary growth factor for the red cell lineage which regulates the survival, proliferation, and differentiation of erythroid precursors, a few studies showed that treatment with recombinant human Epo increases the platelet counts.^[20]

Thromboembolic complications of IDA are found in the form of only case reports (total 19 cases), the largest series of which also reported 6 such cases;^[21] like our series. [Table 4] presents these 19 cases distributed similarly in all age groups and both sexes though there is a predilection for children below the age of 2 years (10 out of 19) just like our findings.^{[12],[21],[22],[23],[24],[25],[26],[27],[28]} 5 cases had normal platelet count, 10 had mild RT, and 4 cases showed severe thrombocytosis. Severe thrombocytosis is not seen in the present study, but otherwise, the findings are similar. None of these studies investigated other platelet parameters which showed some ill-defined pattern in our cases.

Table 4: Previous studies showing hemostatic disorders in iron deficiency anemia

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Conclusions

We conclude that thromboembolic complications are a definite and life-threatening form of presentation in IDA. The role of platelet qualitative changes is more than quantitative ones as seen with our and previous studies which leads to thromboembolic phenomenon in IDA and this definite risk cannot be anticipated from routine hematological investigations or platelet parameters alone. Study of platelet functions in a large series of such complicated cases of IDA is recommended to explore qualitative abnormalities of platelets.

Financial support and sponsorship

We would like to acknowledge Kasturba Health Society, Sevagram, Wardha, Maharashtra, India, for funding for this study.

Conflicts of interest

There are no conflicts of interest.

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