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O R I G I N A L A R T I C L E

Evaluation of blood platelet count and function in patients

with erectile dysfunction

M. Aldemir1, F. Akdemir1, E. Okulu1, K. Ener1, A. Ozayar1 & A. Gudeloglu2

1 Department of Urology, Ankara Atat€urk Training and Research Hospital, Ankara, Turkey; 2 Department of Urology, Memorial Ankara Hospital, Ankara, Turkey

Keywords

Erectile dysfunction—mean platelet volume— platelet distribution width—platelet volume Correspondence

Assoc. Prof. Mustafa Aldemir, Ankara Ataturk Training and Research Hospital Bilkent, Ankara 06800, Turkey. Tel.: +90 533 6309102; Fax: +90 312 2912705; E-mail: drmaldemir@mynet.com Accepted: March 13, 2015 doi: 10.1111/and.12430 Summary

We evaluated and compared blood total platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) values of patients with erectile dysfunction (ED) and control subjects. A total 57 male patients (mean age 49.7 12 years) with ED and 59 control men (mean age 49.7  10.7 years) were included in the study. All patients were evaluated using medical history with International Index of Erectile Function (IIEF) scores, physical examina-tion and routine blood analysis. Total blood count, including white blood cell (WBC), total platelet counts, MPV and PDW parameters, were recorded in both groups. MPV values were detected to be significantly higher in patients with ED than control group: 10.7 1 and 9.72  1.5, respectively (P = 0.001). Similarly, PDW values were significantly higher in patients with ED than control group: 14.6  2.8 and 12.9  1.9, respectively (P = 0.001). However, mean platelet and mean WBC counts were similar in both groups (P = 0.45). We demonstrated that MPV and PDW values significantly increased in patients with ED compared with the control group. According to these findings, platelet function might play an important role in patients with ED that warrants further research.

Introduction

Platelets are circulating, anucleate, disc-shaped cells, the count of which varies over the considerable range of 150 000 to 400 000 per mm3. Their main role is to main-tain the integrity of blood vessels through adequate haemostasis (Frojmovic & Milton, 1982). Circulating platelets may differ in size and haemostatic potential (Frojmovic & Milton, 1982; van der Loo & Martin, 1997). Larger platelets contain more granules and pro-duce greater amounts of vasoactive and prothrombotic factors (Bath & Butterworth, 1996). Mean platelet volume (MPV) and platelet distribution width (PDW) are a mar-ker of platelet activation, which plays an important role in the pathophysiology of thrombosis and is measured as a part of the complete blood count. Platelet activation leads to changes in platelet shape with increase in platelet swelling leading to an increase in MPV and PDW (Boos & Lip, 2007).

Although MPV value was investigated in patients with ED in previous studies (La Vignera et al., 2014; Ciftci et al., 2015), PDW value has not been investigated in the

literature. Herein, we evaluated and compared the total platelet count, MPV and PDW values of patients with ED and control subjects.

Material and methods

A total 57 male patients (mean age 49.7 12, range 24–68 years) with ED were included in the retrospectively study. All patients were evaluated using medical history and sexual history with International Index of Erectile Function (IIEF) scores, physical examination and routine blood analysis. IIEF-5 and IIEF-15 erectile function (EF) domain scores were recorded in all patients. The study did not include those patients who had a systemic disease such as malignancy, hepatic or renal failure, haematologi-cal disorder and active infection; those who underwent any operation or cardiovascular intervention within the previous 3 months; and those who underwent any medi-cal treatment such as intake of antiplatelet or anticoagu-lant drugs in the previous 4 weeks.

Fifty-nine control men (mean age 49.7 10.7, range 26–66 years), healthy, sexually active and age-matched

© 2015 Blackwell Verlag GmbH 189

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men, who had EF domain score >21 by IIEF-5 form were selected as the control group (Group 2).

Total blood count, including haemoglobin, white blood cell (WBC), total platelet count, MPV and PDW parame-ters, were recorded in both groups. Blood samples were drawn from the antecubital vein after an overnight fast. Blood samples were collected in dipotassium EDTA-containing tubes. All measurements were taken immedi-ately after venpuncture to prevent in vitro platelet activation. In addition, fasting blood glucose value was recorded in both groups.

Statistical analysis

Data were presented as mean SD. SPSS version 11.5

software (Chicago, IL, USA) was used for data analysis. Kolmogorov–Smirnov test was used for a normal distri-bution before analysis. Independent-samples t-test was used to compare Groups 1 and 2. A statistically signifi-cant difference was accepted when the P value was lower than 0.05.

Results

Mean patient age was 49.7  12 years (range 24–68) and 49.7 10.7 years (range 26–66), respectively, in Groups 1 and 2 (P > 0.05). Mean MPV values were significantly higher in patients with ED than control group: 10.7 1 and 9.72  1.5, respectively (P = 0.001). Similarly, mean PDW values were significantly higher in patients with ED than control group: 14.6 2.8 and 12.9  1.9, respec-tively (P= 0.001). In addition, fasting blood glucose val-ues were significantly higher in patients with ED than control group: 110.9 33.6 and 97.8  39.5, respectively (P = 0.05). However, mean platelet and mean WBC counts were not statistically significant in Groups 1 and 2 (P = 0.45). The results and IIEF scores are shown in Table 1.

Discussion

The effect of increased platelet activity on vascular disor-ders has been noted in several studies (Coppinger et al., 2004). Platelets have a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation or apposition after plaque rupture. The MPV is a marker of platelet function, and large platelets con-tain more dense granules and produce more thrombox-ane-A2 (Chu et al., 2010).

In our study, we found that the mean MPV and PDW values were significantly higher in patients with ED than in the controls (P= 0.001). Mean platelet volume is a measurement that describes the average size of platelet cells in the blood. The PDW is a measure of platelet anisocytosis. PDW seems to be a more specific indicator of platelet activation than MPV, as it was not elevated during single platelet distention caused by platelet swell-ing. The increased PDW probably reflects a dysregulation in thrombopoiesis, which is also translated by the multi-ple abnormalities of platelet reactivity and the change in platelet membrane and adenine nucleotide content that have been previously described (Leoncini et al., 1990). The combined use of MPV and PDW could predict the activation of coagulation more efficiently. Although, MPV value was investigated in patients with ED in previous studies (La Vignera et al., 2014; Ciftci et al., 2015), PDW value has not been investigated in literature. Mean plate-let volume and PDW values of patients with ED and con-trol subjects were evaluated and compared in this study.

Ciftci et al. (2015) found that the MPV and platelet values were significantly higher in patients with vasculo-genic ED than in patients with post-prostatectomy ED and control group. In the same study, there was no sig-nificant difference among the three groups in terms of WBC values and haemoglobin level (Ciftci et al., 2015). However, PCDU parameters were not specified in their study (Ciftci et al., 2015). Another study showed that

Group 1 (N= 57) Mean SD (range)

Group 2 (N= 59)

Mean SD (range) P-value

Age 49.7 12 (24–68) 49.7 10.6 (26–66) 0.98

PLT (Kll 1) 232.1 53.2 (148–461) 239.8  58 (143–411) 0.45

MPV (fL) 10.7 1 (8.1–13.1) 9.72 1.5 (7–13.3) 0.001

PDW (fL) 14.6 2.8 (9.7–20.3) 12.9 1.9 (8.9–17.9) 0.001

WBC (Kll 1) 7.8 2.1 (3.7–18.6) 7.4 1.7 (4.4–13.5) 0.24

Fasting blood glucose (mg dL 1) 110.9 33.6 (59–217) 97.8 39.5 (30–231) 0.05

IIEF– 5 scores 8.2 3.4 (0–16) 23.8 0.8 (22–25) 0.001

IIEF– 15 EF scores 18.1 3.5 (5–23) 27.8 0.9 (26–30) 0.001

PLT, platelet; MPV, mean platelet volume; PDW, platelet distribution width, WBC, white blood cell; IIEF, International Index of Erectile Function; EF, erectile function.

Table 1 Blood parameters and statistical analysis of Group 1 and Group 2

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Andrologia 2016, 48, 189–192

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patients with arterial ED had a significantly higher MPV and a higher percentage of platelets expressing the vitro-nectin receptor (aVb3) (La Vignera et al., 2014).

Platelets have been suggested to have a role in the pathogenesis of ED. Particularly in vasculogenic ED, platelets were suggested to stick to the cavernosal walls and secrete mediators, leading to an increase in oxidative stress during erection (Jeremy et al., 2000). We have shown in our previous study that a 3-week pistachio diet applied to patients with ED resulted in a significant improvement in erectile function parameters (PCDU parameters and IIEF scores) with additional improvement in serum lipid parameters and significant decrease in blood platelet counts (Aldemir et al., 2011). Our addi-tional previous study demonstrated that mean blood platelet count was found to be significantly increased in patients with ED compared with the control group. Besides, a significant positive correlation was detected between platelet count and oxidative stress parameters, and a significant negative correlation was found between antioxidant parameters (Aldemir et al., 2012). These find-ings suggest that platelets also seem to be contributing to the oxidative stress in patients with ED. We speculate that platelets might carry out this task by producing reactive oxygen species products.

Nitric oxide (NO), synthesised by NO synthase (NOS), activates soluble guanylyl cyclase (sGC) in smooth muscle vascular cells and platelets (Azuma et al., 1986; Walford & Loscalzo, 2003). This activation results in cGMP pro-duction and decreased intracellular calcium concentration (Rao et al., 1990). These variations of second messengers promote vasodilatation mediated by protein kinase G (PKG) and inhibition of platelet activation (Cerra & Pel-legrino, 2007). Cyclic nucleotides are catabolised by a group of enzymes called phosphodiesterases (PDE). Two of them, PDE3 and PDE5 are expressed in platelets and vascular smooth muscle cells (Omori & Kotera, 2007).

Rodrigues et al. (1998) showed that selective penile accumulation of platelets occurred during prostaglandin E1 (PGE1) or papaverine-/phentolamine-induced erec-tion. These data suggest a key role of platelets in the cor-pus cavernosum during erection.

In our study, we found that the mean platelet count and mean WBC value were not statistically significant in Groups 1 and 2 (P= 0.45). Yang et al. (2006) reported that increases in platelet volume are often associated with decreases in platelet count.

Conclusions

Mean platelet volume and PDW is a marker of platelet function that is easily measured by automated blood counters. Our results showed that MPV and PDW values

significantly increased in patients with ED compared with the control group. According to these findings, platelet function might be important in patients of ED that war-rants further research.

References

Aldemir M, Okulu E, Neselioglu S, Erel O, Kayigil O (2011) Pistachio diet improves erectile function parameters and serum lipid profiles in patients with erectile dysfunction. Int J Impot Res 23:32–38.

Aldemir M, Okulu E, Neselioglu S, Erel O, Ener K, Kayigil O (2012) Evaluation of serum oxidative and antioxidative status in patients with erectile dysfunction. Andrologia 44:266–271.

Azuma H, Ishikawa M, Sekizaki S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411–415.

Bath PM, Butterworth RJ (1996) Platelet size, measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 7:157–161.

Boos CJ, Lip GY (2007) Assessment of mean platelet volume in coronary artery disease - what does it mean? Thromb Res 120:11–13.

Cerra MC, Pellegrino D (2007) Cardiovascular cGMP-generating systems in physiological and pathological conditions. Curr Med Chem 14:585–599.

Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Reilly MP, Berger JS (2010) Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 8:148–156.

Ciftci H, Gumusß K, Yagmur _I, Sahabettin S, Cßelik H, Yeni E, Savas M, Gulum M (2015) Assessment of mean platelet volume in men with vasculogenic and nonvasculogenic erectile dysfunction. Int J Impot Res 27:38–40.

Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, Cahill DJ, Emili A, Fitzgerald DJ, Maguire PB (2004) Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 103:2096– 2104.

Frojmovic MM, Milton JG (1982) Human platelet size, shape, and related functions in health and disease. Physiol Rev 62:185–261.

Jeremy JY, Angelini GD, Khan M, Mikhailidis DP, Morgan RJ, Thompson CS, Bruckdorfer KR, Naseem KM (2000) Platelets, oxidant stress and erectile dysfunction: an hypothesis. Cardiovasc Res 46:50–54.

La Vignera S, Condorelli RA, Burgio G, Vicari E, Favilla V, Russo GI, Cimino S, Morgia G, Calogero AE (2014) Functional characterization of platelets in patients with arterial erectile dysfunction. Andrology 2: 709–715.

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Leoncini G, Maresca M, Buzzi E, Piana A, Armani U (1990) Platelets of patients affected with essential thrombocythemia are abnormal in plasma membrane and adenine nucleotide content. Eur J Haematol 44:

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Omori K, Kotera J (2007) Overview of PDEs and their regulation. Circ Res 100:309–327.

Rao Gh, Krishnamurthi S, Raij L, White JG (1990) Influence of nitric oxide on agonist-mediated calcium mobilization in platelets. Biochem Med Metab Biol 43: 271–275.

Rodrigues M, O’Grady J, Stackl W, Granegger S, Sinzinger H (1998) Accumulation of platelets as a key mechanism of human erection. Thromb Res 91:53–56.

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Yang A, Pizzulli L, Luderitz B (2006) Mean platelet volume as marker of restenosis after percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris. Thromb Res 117:1023–1034.

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Şekil

Table 1 Blood parameters and statistical analysis of Group 1 and Group 2

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