Hemorheological parameters in patients with fibromyalgia syndrome

Abstract

AIM: To evaluate hemorheological parameters in patients with fibromyalgia syndrome (FMS) in order to elucidate the etiology of the disease.

METHODS: Twenty-three adult FMS patients and 20 healthy controls were enrolled in the study. Diabetics, hypertensives and those with any rheumatological disorder or use drugs or smoking cigarette were excluded from the study. Following parameters were analyzed in each subject; erythrocyte deformability, erythrocyte aggregation, plasma viscosity, complete blood count, fasting blood glucose, fibrinogen, albumin, globulin and lipid profile.

RESULTS: Erythrocyte elongation indices indicating deformability of erythrocytes were higher in FMS patients (0.564±0.002 at 16.87 mPa and 0.605±0.002 at 30 mPa shear rate) than controls (0.558±0.001 at 16.87 mPa and 0.600±0.003 at 30 mPa shear rate). Erythrocyte aggregation speed was higher in FMS patients (2.1±0.1 s) than controls (2.3±0.2 s). Erythrocyte aggregation index was also higher in FMS patients (65.5±1.3) than controls (62.9±1.5). Erythrocyte aggregation amplitude and plasma viscosity values were similar in both groups (both p > 0.05). Among the complete blood count and biochemical parameters, only albumin levels were lower in the FM patients than controls (p < 0.05).

CONCLUSION: Our results indicate higher erythrocyte deformability and quicker erythrocyte aggregation in FM patients.

Keywords

Erythrocyte aggregation blood viscosity erythrocyte deformability erythrocyte hemorheology plasma viscosity fibromyalgia

1 Introduction

Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread musculoskeletal pain, tender points, sleeping disorders and fatigue [1]. Its prevalence is about 2–8% in the population [2]. Although FMS can be observed in all age groups, it generally affects ages of 40 to 60 and occurs more commonly in women. It may co-occur with irritable bowel syndrome, temporomandibular pain and psychological distress such as depression or anxiety problems [3 –5]. FMS may also occur concurrently with chronic inflammatory diseases such as osteoarthritis, rheumatoid arthritis and systemic lupus erythematosus [6] in which there is preliminary evidence suggesting disturbed blood rheology [7].

The cause of FMS remains unclear but a number of factors including abnormalities in neuroendocrine and autonomic nervous systems, genetic factors, psychosocial variables and environmental stressors are suggested to contribute to the pathophysiology. For example, alterations in autonomic nervous system function involve decreased microcirculatory vasoconstriction [5]. It is claimed that there is autonomic nervous system dysfunction and impaired sympathetic response [8]. Biological amines and neurotransmitters seem to play an important role in the etiology of FMS. Decreased levels of serum tryptophan, serotonin, somatomedin C, neuropeptide Y, growth hormone, and increased levels of nerve growth factor and substance P in cerebrospinal fluid have been reported inFMS [9].

Morf et al. [10] have reported both functional and morphological microcirculatory abnormalities in FMS patients. Peripheral blood flow was lower in FMS patients than controls. These findings were accompanied by fewer capillaries in the nail fold and significantly more capillary dilatations. Jeschonneck et al. [11] have evaluated blood flow in the skin above five tender points in FMS patients by laser Doppler flowmetry, and found that blood flow is reduced in the skin above the tender points in the muscles of FMS patients.

Despite intensive research, etiopathogenesis of FMS is not clarified sufficiently. It was hypothesized that skeletal muscle and skin microcirculation was attenuated in FMS [10 –12]. We hypothesized that the microcirculatory problems in FMS patients were related with negative alterations in hemorheological parameters. Therefore, we investigated the hemoreheological parameters of FMS patients with those of healthy controls.

2 Methods

The study protocol was approved by the local Ethical Committee of the Hacettepe University and, followed the tenets of the Helsinki declaration. Before all participants gave written informed consent for all procedures, they were fully informed of potential risks and benefits of the study as well as their rights as research study subjects.

Twenty-three premenopausal consecutive patients with FMS from the Department of Physical and Rehabilitation Medicine in Hacettepe University, and 20 premenopausal healthy women were included. Smokers, subjects with dyslipidemic profiles, hyperinsulinemia, obesity or subjects taking any kind of medication were excluded from the study. Subjects were tested on the appropriate days (follicular phase; 3rd to 7th days, luteal phase; 18th to 22nd days) of their next cycle after the interview. Since microcirculation is affected from menstrual cycle, in order to achieve similar physiological conditions between control and patient group, such an arrangement in blood withdrawal was set [13]. Patients met the American College of Rheumatology (ACR) FMS diagnostic criteria [3].

2.1 Measurements of biochemical and hemorheological parameters

Fasting blood samples were collected from all subjects at 10 : 00 a.m for measurement of hemorheological parameters, hemoglobin, hematocrit, platelet, total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), triglycerides, albumin, globulin, total protein, glucose and fibrinogen levels. Erythrocyte deformability, erythrocyte aggregation and plasma viscosity measurements were performed within 2-hour of sampling. Blood counts were performed with Coulter counter.

2.1.1 Erythrocyte deformability measurements

Erythrocyte deformability was measured with Laser-Assisted Optical Rotational Cell Analyzer (LORCA) (Mechatronics, Holland). Shear rates were between 0.3 to 30 mPa (0.30, 0.53, 0.90, 1.69, 3, 5.33, 9.49, 16.87 and 30 mPa). Temperature was set to 37°C. Decrease in the elongation index (EI) indicates decrease in deformability [14].

2.1.2 Erythrocyte aggregation measurements

Prior to erythrocyte aggregation measurements, blood was oxygenated for at least 15 minutes. Measurements were performed with LORCA at 37°C. Analysis of the syllectogram by a computer program produces the aggregation amplitude (AMP, yielding total amplitude of the aggregation), aggregation index (AI, indicating how great and/or quick aggregation) and also aggregation half time (t_1/2, time needed for the peak intensity to become half, an indicator for the kinetics of aggregation) [14].

2.1.3 Plasma viscosity measurement

Plasma viscosity was measured using 0.5 ml plasma, with a cone-plate viscometer (Brookfield LVDV-II+PRO CP40, USA) at 900 s-1 (120 rpm) shear rate and at 37°C.

2.2 Statistical analysis

Statistical analyses were performed by SPSS 20 for Windows (IBM, Chicago, USA) by using Mann-Whitney U test for non-parametric variables. Data are presented as mean±standard error of mean (SEM). Spearman correlation coefficient was used for correlation analyses. A p value <0.05 was accepted as statistically significant.

3 Results

Mean age of the control group was 44.8±10.6 years, whereas that of the FMS group was 46.4±2.9 years (p > 0.05). Complete blood count and biochemical parameters were similar between the groups, except for albumin level that was lower in the FMS group than control group (Tables 1 and 2).

Table 1
Blood count parameters in control and fibromyalgia groups

FMS patients Controls p

RBC (x10⁶/mm³) 4.4±0.1 4.5±0.1 NS

Hemoglobulin (g/dL) 13.1±0.2 13.4±0.2 NS

HTC (%) 38.0±0.6 39.6±0.7 NS

Platelet (x10³/mm³) 265.1±11.3 248.7±12.6 NS

	FMS patients	Controls	p
RBC (x10⁶/mm³)	4.4±0.1	4.5±0.1	NS
Hemoglobulin (g/dL)	13.1±0.2	13.4±0.2	NS
HTC (%)	38.0±0.6	39.6±0.7	NS
Platelet (x10³/mm³)	265.1±11.3	248.7±12.6	NS

RBC; red blood count, HTC; hematocrit, FMS; fibromyalgia syndrome, NS; not significant.

Table 2

Biochemical parameters in control and fibromyalgia groups

	FMS patients	Controls	p
TC (mg/dL)	206.3±14.1	199.4±9.8	NS
LDL (mg/dL)	138.2±9.9	130.5±8.9	NS
HDL (mg/dL)	53.5±3.2	61.7±3.0	NS
TG (mg/dL)	109.9±12.3	94.4±10.5	NS
Alb (g/dL)	4.36±0.1	4.51±0.1	<0.05
Glo (g/dL)	2.70±0.1	2.61±0.1	NS
TP (g/dL)	7.06±0.1	7.11±0.1	NS
Glu (mg/dL)	85.5±2.2	88.3±2.2	NS
Fib (mg/dL)	333.3±13.8	329.6±12.7	NS

TC; total cholesterol, LDL; low density lipoprotein, HDL; high density lipoprotein, TG; triglycerides, Alb; albumin, Glo; globulin, TP; total protein, Glu; glucose, Fib; fibrinogen, FMS; fibromyalgia syndrome, NS; not significant.

Erythrocyte elongation indices at 16.87 and 30 mPa shear stresses were found to be higher inFMS patients than controls (both p < 0.005). Our results indicate a higher deformability property for FMS patients (Table 3). Aggregation amplitude (AMP) and plasma viscosity values were similar between the groups (both p > 0.05), t_1/2 was shorter and AI was higher in FMS patients than controls (Table 4).

Table 3

Erythrocyte deformability values in control and fibromyalgia groups

	FMS patients	Controls	p
0.30 mPa	0.039±0.004	0.033±0.004	NS
0.53 mPa	0.055±0.003	0.051±0.003	NS
0.90 mPa	0.110±0.004	0.104±0.003	NS
1.69 mPa	0.208±0.005	0.205±0.003	NS
3 mPa	0.320±0.005	0.321±0.003	NS
5.33 mPa	0.428±0.004	0.430±0.002	NS
9.49 mPa	0.508±0.003	0.504±0.001	NS
16.87 mPa	0.564±0.002	0.558±0.001	<0.05
30 mPa	0.605±0.002	0.600±0.003	<0.05

Erythrocyte deformability values at 0.30, 0.53, 0.90, 1.69, 3, 5.33, 9.49, 16.87 and 30 mPa shear stress. FMS; fibromyalgia syndrome, NS; not significant.

Table 4

Erythrocyte aggregation and plasma viscosity in control and fibromyalgia groups

	FMS patients	Controls	p
AMP (au)	16.75±0.48	17.00±0.64	NS
AI (%)	65.49±1.31	62.94±1.51	<0.05
t1/2 (s)	2.06±0.13	2.34±0.18	<0.05
Viscosity (mPa.s)	1.35±0.01	1.34±0.01	NS

AMP; erythrocyte aggregation amplitude, AI; aggregation index, t1/2; erythrocyte aggregation half time, s; second, FMS; fibromyalgia syndrome, NS; not significant.

In control group erythrocyte deformability (measured at 16.87 and 30 mPa) were found correlated with red blood count (r= 0.439, p = 0.046), hemoglobin (r= 0.456, p = 0.038), globulin (r= 0.514, p = 0.024) and total protein (r= 0.577, p = 0.006) levels; AMP with hemoglobin (r= 0.650, p = 0.001), hematocrit (r= 0.521, p = 0.015) levels; AI with t1/2 (r= –0.991, p = 0.0001), plasma viscosity (r= 0.524, p = 0.010), red blood count (r= 0.438, p = 0.047), hemoglobin (r= 0.472, p = 0.031), hematocrit (r= 0.568, p = 0.007), LDL (r= 0.598, p = 0.004) levels and t1/2 with AI (r= –0.991, p = 0.0001), plasma viscosity (r= –0.494, p = 0.017), red blood count (r= –0.461, p = 0.036), hemoglobin (r= –0.471, p = 0.031), hematocrit (r= –0.570, p = 0.007) and LDL (r= –0.618, p = 0.003) levels.

In FMS group AI was found correlated with t1/2 (r = –0.997, p = 0.0001), red blood count (r= 0.552, p = 0.006), total cholesterol (r= 0.526, p = 0.036), LDL (r= 0.530, p = 0.011), triglyceride (r= 0.452, p = 0.040) and fibrinogen (r= 0.658, p = 0.001) levels and t1/2 with AI (r= –0.997, p = 0.0001), red blood count (r= –0.565, p = 0.005), total cholesterol (r= –0.524, p = 0.037), LDL (r= –0.531, p = 0.011), triglyceride (r= –0.453, p = 0.039) and fibrinogen (r= –0.676, p = 0.0001) levels. No significant correlation was found for erythrocyte deformability (measured at 16.87 and 30 mPa) and AMP with researched parameters in FMS group.

4 Discussion

Fibromyalgia syndrome (FMS) is a common chronic disorder with eminent symptoms. However, its relation with microcirculation and blood viscosity is not yet clearly defined. Therefore, this study was performed to provide data for a possible relationship between FMS and hemorheological parameters. This study has revealed that erythrocytes of FMS patients have higher deformability than controls. In FMS patients, erythrocytes also had quicker aggregation with higher aggregation indices.

The elongation indices were found significantly higher in FMS patients at 16.87 and 30 mPa. In addition elongation indices of FMS group are found higher in most of the shear rates although not statistically significant. These results suggest that FMS patients have better deformability than controls. In a study by Simpson and O’Neill, shape of red blood cells was found to be altered in FMS patients [15]. A higher ratio of flat erythrocytes was found in FMS patients than controls. High surface area/volume ratio of erythrocytes is essential for maintaining their oxygen carrying capacity as well as their capability to deform during passage through the capillary bed. Although not measured in the above mentioned study if flat cells have a higher surface area/volume ratio this may be the cause of better deformability. Alteration of red blood cell shape may exert a substantial impact on their rheological behavior. Although we didn’t focus on the alterations in the shape of the red blood cells, our observation on erythrocyte deformability might be related with the change in shape.

We were not able to reach any report on hemorheological study in FMS patients. Although erythrocyte deformability (measured at 6 Pa) was found to be lower in some chronic inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) [7] which may concurrently occur with FMS [6] it has not been evaluated in patients with FMS so far. In the study by Santos et al., patients with SLE and RA had lower blood viscosity, lower erythrocyte deformability and increased erythrocyte aggregation than controls, therefore presenting a less favorable hemorheological status [7]. One of the major findings of our study was the increased erythrocyte deformability in FMS. Taking into consideration the major contribution of erythrocyte deformability to blood viscosity, decreased erythrocyte deformability results in increased blood viscosity which may then hamper the microcirculation [16 –18]. According to our results, it is possible to state that erythrocyte deformability property of blood is not adversely affected in FMS patients. Our study demonstrates a slight decrease in hematocrit levels in FMS patients without statistical significance.

In the present study plasma viscosity values were similar between the groups. Our findings are in contradiction with that of Al-Allaf et al. [19] who found higher plasma viscosity values in FMS patients than controls. On the other hand, mean hemoglobin value of control group was 13.4 g/dL, whereas it was 13.1 g/dL in FMS group in this study. Recently, Mader et al. reported [20] that hemoglobin values of both groups were found to be same. However, another study found significantly higher hemoglobin values in FMS group (14.4 g/dL) when compared to control group (14.2 g/dL) [21]. Also comparison of our results with other authors reveal similar trends in lipid profile [21 –23]. In all of those studies FMS patients had unfavorable lipid profiles compared to controls.

In conclusion our results have revealed changes in hemorheological parameters in FMS patients. Whether these findings can explain the microcirculatory findings in FMS patients needs studies that combine flow measurements with hemorheologic evaluation.

Footnotes

Acknowledgments

This study was supported by Hacettepe University Scientific Research Administration.

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Hemorheological parameters in patients with fibromyalgia syndrome

Abstract

Keywords

1 Introduction

2 Methods

2.1 Measurements of biochemical and hemorheological parameters

2.1.1 Erythrocyte deformability measurements

2.1.2 Erythrocyte aggregation measurements

2.1.3 Plasma viscosity measurement

2.2 Statistical analysis

3 Results

Table 1 Blood count parameters in control and fibromyalgia groups FMS patients Controls p RBC (x106/mm3) 4.4±0.1 4.5±0.1 NS Hemoglobulin (g/dL) 13.1±0.2 13.4±0.2 NS HTC (%) 38.0±0.6 39.6±0.7 NS Platelet (x103/mm3) 265.1±11.3 248.7±12.6 NS

Footnotes

Acknowledgments

References

Table 1
Blood count parameters in control and fibromyalgia groups

FMS patients Controls p

RBC (x10⁶/mm³) 4.4±0.1 4.5±0.1 NS

Hemoglobulin (g/dL) 13.1±0.2 13.4±0.2 NS

HTC (%) 38.0±0.6 39.6±0.7 NS

Platelet (x10³/mm³) 265.1±11.3 248.7±12.6 NS