Medical Journal of Dr. D.Y. Patil Vidyapeeth

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 10  |  Issue : 4  |  Page : 370--375

Diagnostic implication of mean platelet volume in thrombocytopenia


Ishita Gulati, Harsh Kumar, Jay Sheth, Indranil Dey 
 Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India

Correspondence Address:
Ishita Gulati
Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Center, Pimpri, Pune - 411 018, Maharashtra
India

Abstract

Background: A well-known cause of thrombocytopenia is peripheral platelet destruction in which the circulating platelets are premature and large. Many times a bone marrow examination is conducted to find out the etiology of thrombocytopenia. Assessment of platelet parameters like mean platelet volume (MPV) generated by a hematology analyzer is also believed to be helpful for guiding the clinicians to identify such cases. Aims: This study aims to ascertain whether raised MPV correlates with thrombocytopenia due to hyperdestruction of platelets. Materials and Methods: This was 2 years unicentric prospective observational study which included 100 thrombocytopenic patients. Their clinical diagnosis, platelet counts, and MPV values were recorded. Peripheral blood smears (PBS) were also examined for megaplatelets. Each case was put in Group A (hyperdestructive etiology) or Group B (hypoproductive etiology). Results: Group A had 79 cases out of which 53 had an MPV value more than 10.5 fl. In the rest, although MPV was not prominently raised, the PBS did show megaplatelets. Group B had 21 cases, which were not associated with a high MPV. A receiver operating characteristic curve was plotted, and Youden's index was used to find out a cutoff value for MPV (8.5 fl) which gave the maximum sensitivity and specificity to discriminate thrombocytopenia cases of hyperdestructive etiology from the rest. Conclusion: MPV is an accurate, reliable, and easily obtained platelet parameter which is helpful in diagnosing the basic etiology of thrombocytopenia. It is also a less painful alternative than the bone marrow examination for the patient.



How to cite this article:
Gulati I, Kumar H, Sheth J, Dey I. Diagnostic implication of mean platelet volume in thrombocytopenia.Med J DY Patil Univ 2017;10:370-375


How to cite this URL:
Gulati I, Kumar H, Sheth J, Dey I. Diagnostic implication of mean platelet volume in thrombocytopenia. Med J DY Patil Univ [serial online] 2017 [cited 2024 Mar 28 ];10:370-375
Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2017/10/4/370/213941


Full Text

 Introduction



Thrombocytopenia is a reduction in the peripheral blood platelet count below 150,000/μl. Two main mechanisms involved in the pathogenesis of thrombocytopenia are: (a) increased peripheral platelet destruction and (b) a decreased platelet production by the bone marrow.[1] Differentiation between these two etiopathologies is ascertained by a bone marrow examination which is, unfortunately, invasive and painful.

Normal platelets measure 1–4 μm in diameter on PBS.[2] Mean platelet volume (MPV) is generated by an electronic cell counter, which indicates the average volume of the circulating platelets. Its normal range is 7–10.5 fl.[3] It has been observed that platelets have a high MPV in hyperdestructive thrombocytopenia cases.[4] These large/giant platelets (approximately more than three times the normal size) observed in the circulation are young and metabolically active, which are released by the bone marrow as compensation for losses. This study attempts to analyze the role of MPV as a simple test for distinguishing these two types of thrombocytopenic etiologies.

 Materials and Methods



This was a unicentric prospective observational study carried out at a tertiary care center for 2 years. The study included fresh 100 consecutive cases with thrombocytopenia having platelet count <150,000/μl. An Institutional Ethics Committee Clearance was obtained before the start of the study. Cases were identified on a daily basis from the hemogram reports generated in the hospital laboratory. Platelet counts 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 - Group A included all cases of thrombocytopenia due to hyperdestructive etiology, and Group B included all cases of thrombocytopenia due to hypoproductive etiology. Special efforts were made to identify megaplatelets on PBS. Our laboratory has a three part differential hematology analyzer Sysmex KX 21, which works on the principle of electronic impedance. The MPV for each patient was recorded from the cell counter report. Each sample was run on the machine soon after collection to avoid false high MPV value due to EDTA-induced platelet swelling. All cases underwent bone marrow examination in the hypoproductive group (n = 21). The bone marrow findings were commensurate with the diagnosis. In the hyperdestructive group, bone marrow examination was performed only if indicated as in idiopathic thrombocytopenic purpura (ITP), drugs, hypersplenism, dengue, etc., (n = 33), and not in cases with infection. The bone marrow in the hyperdestructive group was normocellular to mildly hypercellular. All the three hematopoietic lines did not show any significant abnormality. This effectively ruled out thrombocytopenia due to bone marrow failure. In addition, MPV of fifty healthy controls were also obtained from the laboratory records. They were undergoing a routine medical check-up or minor elective surgery. The data were documented in Microsoft Excel and were analyzed to correlate the platelet size and MPV with the patient diagnosis.

 Results



Of the 100 cases studied, males were 61 and females were 39. Male to female ratio was 1.56:1. The most common age group of patients was 0–10 years accounting for 24 patients, followed by 11–20 years which included 16 patients. Maximum patients (n = 37) had platelet count in the range of 75,001–100,000/μl, followed by 25,001–50,000/μl range which had 32 patients. We observed that 53/100 patients had a high MPV value of more than 10.5 fl. They also had megaplatelets on their PBS [Figure 1]. Totally, 35 cases had MPV in the normal range (7–10.5 fl) and 12 cases had MPV value <7 fl.{Figure 1}

The majority of cases in our study belonged to Group A, which were 79 (95% confidence limits for proportion 79/100 - lower 70.2, upper 86.14), of which maximum cases had a clinical diagnosis of dengue fever followed by malaria, sepsis, and other minor causes as shown in [Table 1].{Table 1}

Total cases in Group B were 21 (95% confidence limits for proportion 21/100 - lower 13.86, upper 29.8) of which majority were having megaloblastic anemia followed by acute leukemia, aplastic anemia, drugs, etc., as shown in [Table 2].{Table 2}

Mean MPV of Group A and B patients was 10.85 ± 1.63 fl and 6.95 ± 0.74 fl, respectively. MPV of 50 healthy controls were also recorded which were all within normal range.

Receiver operating characteristic (ROC) curve was plotted for the MPV value of Group A patients [Figure 2]. Area under the curve was 0.982 with a null hypothesis true area set as 0.5. Standard error was 0.011 (95% confidence interval upper - 1.000, lower - 0.961, P < 0.005). More is the ROC curve toward the upper left; better is the study parameter as it increases the area under the curve. In this study, the area under the curve was much higher than 0.5, and hence this shows that MPV is a very good parameter to identify the etiology of thrombocytopenia cases.{Figure 2}

According to Youden's index ([sensitivity + specificity] - 1) calculated from [Table 3], a cut-off MPV value of 8.5 fl showed the maximum sensitivity (92.4%) and specificity (100%). The positive predictive value, negative predictive value, and diagnostic accuracy were 100%, 77.78%, and 94%, respectively. Therefore, findings from our study showed that an MPV value of ≥8.5 fl can be used for diagnosing thrombocytopenia cases due to hyperdestructive etiology.{Table 3}

 Discussion



Peripheral platelet destruction is the most common cause of thrombocytopenia where even the compensatory increase in its production is sometimes not sufficient to keep the counts in the normal range. The differential diagnosis for this in adults is quite broad.

Bone marrow examination is an invaluable but an invasive test. It provides information about platelet production, such as the number and morphology of megakaryocytes. It is necessary for diagnosing certain hematologic diseases such as aplastic anemia, megaloblastic anemia, leukemias, and malignant metastases.[1],[5]

ITP is an autoimmune disorder caused by platelet-specific autoantibodies causing their premature destruction. Another important cause of thrombocytopenia in our country is dengue fever. The anti-dengue virus antibody binds to the dengue antigen associated with platelets, leading to their immune-mediated destruction.[6] Malaria is also a fairly common cause of thrombocytopenia in our setting. Diseases causing thrombocytopenia due to nonimmunologic platelet destruction include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.[5] In the majority of the thrombocytopenia cases of our study with these etiologies, we had found large sized platelets on PBS examination.

It is important to know the etiology of thrombocytopenia for correct patient management and to avoid unnecessary procedures, transfusions, and potentially harmful medications. Thus, new noninvasive diagnostic approaches for thrombocytopenia are needed.

Although our study consisted of predominantly male patients, 6 out of 7 ITP patients were females. The age group with the maximum number of thrombocytopenia cases was 0–10 years. A study by Reddy et al. found 21–30 years as the most common age group.[7] This difference in observations could be due to a larger sample size of 500 in their study.

Majority of cases we studied had a platelet count in the range of 75,001–100,000/μl, followed by 25,001–50,000/μl. More or less, similar observations have been made by other workers.[7],[8]

We encountered more cases of hyperdestructive thrombocytopenia that have been put in Group A (79/100). Maximum cases amongst them were of dengue followed by malaria and sepsis. Dengue fever was also found to be the most common cause among thrombocytopenia patients by Bhalara et al.[9] Rehman et al. and Patel et al. found malaria as the leading cause of thrombocytopenia followed by other infections such as dengue.[10],[11]

MPV is thought to reflect changes in rate of platelet production. We found a high MPV value in 53 cases out of 100, which were all Group A patients. A low MPV was observed in 12 patients that were all of Group B. The MPV in 35 patients fell in the normal range, and they were from both Group A and B.

In our study, mean MPV in Group A patients was higher (10.85 ± 1.63 fl), which is similar to the study done by Reddy et al. (10.59 ± 1.24 fl).[7] Highest mean MPV of 12.9 ± 0.69 fl was seen among the seven ITP cases. With regard to ITP, many studies have been carried out in the past and yielded similar results.[1],[12],[13],[14]

In our study, mean MPV of 10 sepsis patients was 11.83 ± 2.34 fl. Van der Lelie et al. found 13 of 25 patients in sepsis with low mean platelet counts and high MPV which was not related to any particular microorganism.[15] Giles found raised MPV in patients with infections.[3]

In our study, three pregnancy associated thrombocytopenia cases had a mean MPV of 11.13 ± 0.78 fl. Other studies also showed pregnant women having significantly lower platelet counts and high MPV values.[3],[16],[17]

In patients of ischemic heart disease (IHD), high MPV has been found by many workers, thereby prompting some to state that it can be considered as a risk factor for IHD.[16],[18]

The mean MPV of dengue cases in our study was 10.85 ± 1.19 fl. The available literature has conflicting results. Some workers have reported a raised MPV,[7],[19] while Nehara et al. have concluded that dengue is associated with a low MPV.[20] We feel that in this study, the number of dengue cases might not be sufficient to reach a significant conclusion. A similar study involving a larger number of cases would be helpful. The MPV in Grave's disease has been observed to be raised by Panzer et al.[21]

The Group B patients had a low mean MPV value of 6.95 ± 0.74 fl. Reduced MPV in cases with malignant metastases has been found in many studies.[4],[22] Shah et al. found an inverse relationship between MPV and platelet count in cases of anemia which in our country are usually due to nutritional deficiencies.[16] Numbenjapon et al. concluded that the mean MPV of normal Thai population (7.9 fl) may be used as a cut-off to distinguish the two types of thrombocytopenia,[4] which in our study was calculated as 8.5 fl.

Cases as gastrointestinal tract infections, meningitis, human immunodeficiency virus, Grave's disease, posttransfusion purpura, hemolytic uremic syndrome, and ischemic heart disease in Group A and metastasis in Group B were restricted to the single case only. As this is a small number, they are statistically insignificant. Therefore, they have not been discussed or analyzed to avoid bias in conclusion.

The sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index were 100% in a study done by Ntaios et al., who concluded that MPV is absolutely reliable in differentiating ITP from postchemotherapy myelosuppression subgroups, at the cutoff values of 9–10 fl. This result may be due to their selection of the two extreme case categories as ITP is a purely hyperdestructive thrombocytopenia in contrast to the other which is purely hypoproductive.[1]

Furthermore, differences in the mean MPV values of various studies may be because of differences in the machines used and their working principles. Size of the thrombocytes has been studied by Garg et al., who demonstrated that the megathrombocyte percentage in PBS correlates with the number of megakaryocytes in the bone marrow smears and thus with a state of platelet hyperproduction.[23] Vukelja et al. found MPV to be a good indicator of bone marrow production state.[24] Other platelet parameters such as platelet distribution width, platelet large cell ratio, and maximum of the platelet histogram (the highest peak of the bell-shaped platelet log volume distribution curve) are also useful for differentiating the etiology of thrombocytopenia. They have been analyzed by other workers [1],[25],[26],[27] but are not evaluated in our study.

 Conclusion



At present, many types of hematology analyzers are available for analysis of various blood parameters. The newer machines are offering an ever-increasing range of modalities for hemogram and platelet analysis. They use different principles such as electrical impedance, optical light scatter, and fluorescent staining for studying blood cells which are giving encouraging results. Further studies in broader patient groups would enable us to use these newer parameters with greater confidence to offer better patient management. In this study, the determination of MPV was found to be extremely useful in ascertaining the etiology of thrombocytopenia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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