Mean platelet volume in patients with fibromyalgia
- First Online:
- Cite this article as:
- Haliloğlu, S., Carlioglu, A., Sahiner, E. et al. Z. Rheumatol. (2014) 73: 742. doi:10.1007/s00393-013-1330-7
- 173 Downloads
Fibromyalgia is a syndrome characterised by chronic widespread pain at multiple tender points, as well as joint stiffness and systemic symptoms. The aetiology and pathogenesis of fibromyalgia still remain unclear, although many contributory factors have been suggested. The presence of some common features between fibromyalgia and cardiovascular risk factors (e.g. depression and sleep disturbance) led to question of whether there is there a relationship between fibromyalgia and cardiovascular disease and/or atherosclerosis. Mean platelet volume, which is a determinant of platelet activation, is a newly emerging independent risk factor for cardiovascular disease.
The present study was designed to evaluate levels of mean platelet volume in patients with fibromyalgia; the study population consisted of 283 individuals with this syndrome, who were compared with 72 healthy controls. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count and mean platelet volume levels were retrospectively recorded via the computerised patient database. The levels of mean platelet volume were significantly higher in the fibromyalgia group than in the control group (8.09 ± 0.84 fl and 7.73 ± 0.65 fl, respectively, p < 0.001). There were no statistical differences between groups with regard to platelet count and other parameters. These results suggest that an early atherosclerosis marker, mean platelet volume, is elevated in patients with fibromyalgia. This indicates increased platelet activation and therefore a higher risk of future cardiovascular disease.
KeywordsFibromyalgia Mean platelet volume Cardiovascular diseases Risk factors Platelet activation
Mittleres Thrombozytenvolumen bei Patienten mit Fibromyalgie
Fibromyalgie ist ein Syndrom, das durch chronische, an mehreren Tenderpoints verbreitete Schmerzen sowie durch Gelenksteife und systemische Symptome gekennzeichnet ist. Ätiologie und Pathogenese der Fibromyalgie sind immer noch ungeklärt, auch wenn viele mitwirkende Faktoren genannt worden sind. Das Vorliegen einiger gemeinsamer Merkmale von Fibromyalgie und kardiovaskulären Risikofaktoren (z. B. Depression und Schlafstörungen) führte zu der Frage, ob es einen Zusammenhang zwischen Fibromyalgie und Herz-Kreislauf-Erkrankungen und/oder Atherosklerose gebe. Das mittlere Thrombozytenvolumen, ein Parameter der Thromobozytenaktivierung, ist ein neu aufkommender unabhängiger Risikofaktor für Herz-Kreislauf-Erkrankungen.
Mit der vorliegenden Studie sollte die Höhe des mittleren Thrombozytenvolumens bei Patienten mit Fibromyalgie ermittelt werden; die Studienpopulation bestand aus 283 Personen mit diesem Syndrom, welche mit 72 gesunden Kontrollen verglichen wurden. Blutsenkungsgeschwindigkeit, C-reaktives Protein, Leukozytenzahl, Thrombozytenzahl und mittleres Thrombozytenvolumen wurden retrospektiv anhand der elektronischen Patientendatenbank erfasst. Die Werte für das mittlere Thrombozytenvolumen waren in der Gruppe mit Fibromyalgie signifikant höher als in der Kontrollgruppe (8,09 ± 0,84 fl bzw. 7,73 ± 0,65 fl; p < 0,001). Es gab keine statistischen Unterschiede zwischen den Gruppen in Hinblick auf die Thrombozytenzahl und andere Parameter. Diese Ergebnisse sprechen dafür, dass ein früher Atherosklerosemarker, das mittlere Thrombozytenvolumen, bei Patienten mit Fibromyalgie erhöht ist. Das ist ein Anzeichen einer erhöhten Thrombozytenaktivierung und somit eines höheren Risikos zukünftiger Herz-Kreislauf-Erkrankungen.
SchlüsselwörterFibromyalgie Mittleres Thrombozytenvolumen Kardiovaskuläre Erkrankungen Risikofaktoren Plättchenaktivierung
Fibromyalgia (FM) is a syndrome characterised by chronic widespread pain (in any bodily region, including the visceral organs) at multiple tender points, as well as joint stiffness and systemic symptoms (e.g. mood disorders, fatigue, cognitive dysfunction, insomnia, psychological distress and impaired function, including sexual dysfunction) [1, 2, 3, 4]. The American College of Rheumatology (ACR) committee gave an account of the widely used diagnostic criteria for FM in 1990 . More recently, the ACR proposed a new set of such criteria, which include fatigue, waking unrefreshed, cognitive symptoms and somatic (physical) symptoms [6, 7]. The prevalence of FM has been estimated as being approximately 2.9 –4.7 % [8, 9].
Diagnostic criteria for fibromyalgia include fatigue, waking unrefreshed, cognitive symptoms and somatic (physical) symptoms
The aetiology and pathogenesis of FM still remain unclear, although many contributory factors, such as dysfunction of the central and autonomic nervous systems, neurotransmitters, hormones and the immune system, as well as deterioration of muscle microcirculation, decrease of pressure pain threshold, genetic susceptibility, external stressors and psychiatric aspects, among others, have been suggested.
The relationship between FM and sleep disturbance, depression and stress is well known [1, 2, 3, 4]. Furthermore, some studies have pointed to a relationship between cardiac disease and chronic sleep deprivation and depression [10, 11]. The presence of these common features between FM and cardiovascular risk factors led to the question whether there is a relationship between FM and cardiovascular disease and/or atherosclerosis.
Mean platelet volume (MPV) has become a conspicuous and useful parameter because of its relationship with atherosclerosis [12, 13]. MPV, an accurate measure of platelet size, is considered a marker and determinant of platelet function . Larger platelets with higher MPV values are haemostatically more reactive and produce higher amounts of the prothrombotic factor thromboxane A2, increasing propensity to thrombosis . MPV has been reported to be increased in patients with coronary heart disease, diabetes, atherosclerosis, hypertension, hypercholesterolaemia, smoking, renal artery stenosis, polycystic ovary syndrome and subclinical hypothyroidism, obesity, cerebrovascular disease, venous thromboembolism and several chronic inflammatory disorders (systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, ankylosing spondyloarthritis, familial Mediterranean fever and Behçet’s disease) [12, 14, 16, 17, 18]. Furthermore, increased MPV is associated with increased risk of myocardial infarction (MI), independent of known cardiovascular risk factors .
Mean platelet volume is a marker of inflammation and thrombosis
On the basis of this background, it can be considered that MPV might be affected by inflammation and number of platelets, and, consequently, infectious disease. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inflammatory markers, and white blood cell count (WBC) is also increased in infectious disease.
We examined the role of MPV, as well as atherosclerosis, in FM pathogenesis; this study is the first to investigate the relationship between MPV values and FM.
Subjects and methods
The study group consisted of 283 FM patients (mean age 42.5 ± 10.7 years) attending the outpatient Rheumatology Clinic, Faculty of Medicine, Fatih University, Ankara, Turkey, and the control group comprised 72 healthy individuals (mean age 39.5 ± 12 years), attending the Family Practice outpatient clinic for checkups. Any patient known to have chronic inflammatory disorders, hypertension, hypercholesterolaemia or diabetes, using anti-coagulant therapy or having a propensity to thrombotic or bleeding disorders was excluded from the study group. Patients took non-steroid anti-inflammatory drugs as required.
ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), WBC (white blood cell), platelet count and MPV data, obtained during the patients’ last visit, were collected using a computerised patient database.
Complete blood count parameters of healthy individuals were recorded from the same computerised database. The complete blood count analyses were performed using the Beckman/Coulter LH 780 Haematology Analyser (Beckman Coulter, CA, USA), which is routinely checked every month in the central laboratory of the institution. Standard tubes with a constant amount of ethylenediaminetetraacetic acid (EDTA) were used.
All tests were performed in the morning, after 8 h of fasting. All participants were seated for 5 min before blood samples were taken. Tourniquets were applied, and all collections were completed in under 1 min. Venous blood was collected in a 2 ml EDTA tube for complete blood count analyses. Complete blood counts were determined within 2 h of collection, to minimise changes in platelet size, using the same Coulter analyser. The MPV reference range was between 6.9 and 10.8 fl, the intra-assay coefficient of variation (CV) was 0.68 % and the inter-assay CV was 0.95 %.
All statistical analyses were performed using the SPSS for Windows, version 17.0 (Chicago, IL, USA). Unless otherwise stated, results were expressed as means ± standard deviation (SD). The Mann–Whitney U test or independent sample t-test was used between the two participant groups. The Pearson correlation test or Spearman correlation test was used as appropriate. Multiple regression analysis was used to exclude the possible confounding effect of other variables on the result of each correlation analysis, and p < 0.05 was considered statistically significant.
Laboratory parameters of the study population are presented in Tab. 1.
Laboratory parameters of the study population
WBC (× 103/l)
6.73 ± 1.92
6.93 ± 1.87
15.48 ± 11.34
16.12 ± 10.36
5.73 ± 5.26
5.18 ± 4.76
PLT (× 103/l)
263.17 ± 60.78
271.64 ± 78.41
7.72 ± 0.66
8.08 ± 0.84
In patients with FM, the MPV value (8.09 ± 0.84 fl) was significantly higher than in the control participants (7.73 ± 0.65 fl; p < 0.001). The MPV comparison between the two groups is shown in Fig. 1.
There was no statistical difference regarding platelet count and other parameters between FM patients and control participants (Tab. 1). High MPV values were found independent of confounding factors, such as obesity and smoking (Tab. 2).
Multiple regression analysis of factors possibly affecting the MPV in FM group
MPV, which is a determinant of platelet activation, is an independent risk factor for cardiovascular disease [13, 14]. The present study demonstrated that MPV levels were significantly higher in patients with FM, as compared to healthy controls. This was interesting, since MPV is a marker of inflammation and thrombosis, and FM is not known as an inflammatory or thrombotic disease. Conversely, the close relationship between FM and sleep disturbance, stress and depression may corroborate this finding, in terms of susceptibility to cardiac diseases.
MPV levels were significantly higher in FM patients compared to healthy controls
It has been reported that MPV is increased in patients with thrombotic or inflammatory disorders [13, 16, 17, 18]. An inverse relationship between platelet count and MPV in some physiological and pathological conditions, reflecting the tendency to maintain haemostasis by preserving a constant platelet mass, has also been frequently described . This inverse relationship is often observed in inflammatory disorders, in which enhanced thrombopoiesis increases the quantity of circulating platelets, and a large number of highly reactive large-sized platelets migrate to inflammatory sites, where they are intensely consumed . Several hormonal and immune agents influence the maturation of thrombopoietic cells and the release of platelets into the circulation . Of these, thrombopoietin, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1, tumour necrosis factor-α and IL-6 are of importance .
However, in stress conditions, a positive correlation between thrombopoietin, ploidy of platelet progenitors, functional activity and high platelet count is more apparent . The effects of established cardiovascular risk factors on platelet morphology and thrombogenesis (e.g., smoking and obesity) have been investigated and are associated with elevated MPV [23, 24]. A propensity to thrombosis in FM patients can be corrected by association with obesity, stress or smoking [3, 25, 26, 27, 28]. In this study, increased MPV values were found independent of smoking and obesity.
In recent years, MPV has attracted great attention, due to its relationship with coronary heart disease, atherosclerosis, hypertension and other vascular disorders [12, 13, 16, 17, 18]. Large platelets aggregate more rapidly than those of a normal size [12, 16], so it has been suggested that increased MPV values could be associated with an increased risk of atherosclerosis [15, 29]. Higher MPV levels have been reported in various cardiovascular diseases. Klovaite et al.  reported that risk of myocardial infarction (MI) increases with increasing MPV, independent of known cardiovascular risk factors; those with higher MPV values had a greater risk of acute MI .
The present study was the first to evaluate MPV levels in FM patients. Our findings suggest that the elevated MPV, without other cardiovascular risk factors, in these individuals might be considered as a marker of increased cardiovascular disease risk, on the basis of a tendency towards increased platelet activation, which could indicate an increase in the atherosclerotic risk in FM. Investigation of MPV is simple, cheap, routinely used and quick, and could be involved in all types of complete blood counts.
We found that FM patients had higher platelet volumes than control individuals, independently of known cardiovascular risk factors and inflammation. Further research is required to better understand the pathophysiology of these findings.
In conclusion, our results suggest that individuals with FM are susceptible to increased platelet activation and increased MPV values, which contribute to an increased risk of cardiovascular diseases.
Compliance with ethical guidelines
Conflict of interest. S. Haliloğlu, A. Carlioglu, E. Sahiner, Y. Karaaslan, and A. Kosar state that there are no conficts of interest. The accompanying manuscript does not include studies on humans or animals.