Mean platelet volume in patients with increased γ-glutamyl transferase

Abstract

Mean platelet volume (MPV) is the commonly measured platelet index for platelet size and surrogate marker of platelet activation. Changes of MPV in hepatic disease have been evaluated in inflammatory conditions, fibrosis and malignancy. We also had reported previous studies to analyze clinical meaning of MPV in patients with hepatocellular carcinoma and chronic hepatitis B. However, data about investigation of MPV in cholestatic conditions are not sufficient so far. Recently, it has been reported that MPV was increased in intrahepatic cholestasis of pregnancy. In this study, we planned to investigate the relationship between MPV and glutamyltransferase which is well-established laboratory marker for cholestasis, in various disease conditions.

• Cholestasis
• GGT
• liver
• MPV
• platelet
• TPO

Mean platelet volume (MPV) is the commonly measured platelet index for platelet size and surrogate marker of platelet activation [1–6]. Changes of MPV have been evaluated in hepatic disease especially inflammatory conditions (hepatitis), fibrosis (liver cirrhosis) and malignancy (hepatocellular carcinoma, HCC) [5, 6]. We have also reported previous studies to analyze clinical meaning of MPV in patients with HCC and chronic hepatitis B [2, 3]. However, data about investigation of MPV in cholestatic conditions are not sufficiently accumulated so far. Recently, it has been reported that MPV was increased in patients with intrahepatic cholestasis of pregnancy [7]. In this study, we planned to investigate the relationship between MPV and γ-glutamyl transferase (GGT) which is well-established laboratory marker for cholestasis, in various disease conditions [8].

Total 671 results with increased GGT (1.5 times higher than upper reference limit) from 415 different patients were collected for this study in our hospital between March 2012 and April 2012. Among these data, 337 cases having MPV values with CBC test results were finally enrolled as patient group. The control group comprised 143 individuals selected randomly who visited the same hospital for medical check-ups and was used in our previous study [1]. Individuals who had diabetes mellitus or hypertension were excluded from the control group through extensive medical chart review. Platelet index and common blood count (CBC) count were measured using ethylenediaminetetraacetic acid (EDTA) blood in Advia 2120 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY) within 2 h. GGT was tested using Toshiba chemical analyzer (Toshiba, Nasushiobara, Japan). Independent t-test, Pearson correlation analysis and regression study were used to examine the relationships between variables. The statistical analyses were performed with MedCalc v12.7.7 (MedCalc Software, Mariakerke, Belgium).

Mean age of patient group was 55.88 years and male to female ratio was 218:119 (Table I). Patients group presented a broad range of disease entities such as hepatobiliary diseases, cardiovascular diseases, cerebrovascular disease and gastrointestinal diseases. Mean of GGT was 196.05 U/L in the patient group. Platelet counts presented no significant difference between patient and control groups. However, mean of MPV was the significantly increased in patients group (8.7415 fL, range 6.6–16.9 fL) than control group (7.9594 fL, range 6.7–11.0 fL, p < 0.0001, Figure 1A). Especially in male patients, correlation analysis revealed a significant positive correlation between MPV and GGT (Figure 1B, p = 0.0039). There was no significant difference in mean of MPV, platelet count or GGT levels according to the gender.

Figure 1. MPV in patients with increased GGT. MPV is significantly increased in patient group (A, p < 0.0001), and shows the positive correlations with GGT levels in male patient group (B, p = 0.0039).

Table I. Clinical and laboratory characteristics of patient group in this study.

Total number of patients	337
Mean age (years, range)	55.88 (0–88)
Male to female ratio	218:119
Mean of MPV (fL, range)	8.7415 (6.6–16.9)
Mean of platelet count (10^3/µL, range)	246.38 (7–640)
Mean of GGT (U/L, range)	196.05 (75–1388)

Abbreviations: MPV, mean platelet volume; GGT, γ-glutamyl transferase.

In this study, we found that MPV was significantly increased in patients with elevated GGT levels regardless of kinds of underlying diseases. Because liver is the major organ to produce thrombopoietin (TPO) that is the main physiologic regulator of platelet production, further studies should be followed to investigate the relationship of MPV, TPO, and cholestatic conditions expressed by increased GGT [9, 10]. Because the correlation between MPV and GGT was identified only in male patient group, we carefully suggest that female patient may have more complicated and multifactorial factors affecting changes of platelet dynamics, such as sex hormone or postmenopausal change [4, 11]. This study is a pilot one, therefore, there were several confounding factors not evaluated in this time, such as possible effects of cardio- or cerebrovascular comorbidities [12]. In the future, clinical meaning of MPV increase in cholestatic conditions should also be evaluated with longitudinal follow-up, clinical observation, and evaluation of other confounding factors that can influence in MPV levels, especially in the aspect of cardiovascular risk stratification.

Declaration of interest

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013R1A1A3005834). The authors declare no conflicts of interests. The authors alone are responsible for the content and writing of this article. The authors thank Hae Jin Lee for her help in this study.