ORIGINAL ARTICLE Year : 2022  |  Volume : 8  |  Issue : 4  |  Page : 497-501

Hemogram parameters in fibromyalgia and effects of wet cupping therapy on hemogram parameters

Hmeyra Aslaner1, Havva Talay Çalış2, Çağlar Karabaşc3, Ali Ramazan Benli4
1 Department of Family Medicine, Kayseri City Hospital, Kayseri, Turkey
2 Department of Physical Medicine and Rehabilitation, Kayseri City Hospital, Kayseri, Turkey
3 Department of Physical Medicine and Rehabilitation, Kastamonu Rehabilitation Center, Kastamonu, Turkey
4 Karabük University, Medical Faculty, Department of Family Medicine, Karabük, Turkey

Date of Submission21-Apr-2021Date of Acceptance20-Aug-2021Date of Web Publication10-Feb-2022

Correspondence Address:
Hmeyra Aslaner
Department of Family Medicine, Kayseri City Hospital, Şeker, Molu, Kocasinan, Kayseri 38080
Turkey

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/wjtcm.wjtcm_73_21

Objective: Wet cupping therapy (WCT) is one of the complementary and traditional therapies that are still must be scientifically interpreted. This study aimed to assess hemogram parameters that are subclinical inflammatory markers in patients with fibromyalgia syndrome (FMS) and observe how they were affected with WCT. Methods: The present study consisted of two groups; patient group included participants who were diagnosed with FMS and who received WCT and control group included healthy participants who received WCT within the concept of preventive medicine. Results: Neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) values were higher in the patient group (P = 0.029 and P = 0.003, respectively). Considering that the participants had FMS, the optimal cutoff value for PLR was ≥1.62, sensitivity was 70%, specificity was 56%, positive predictive value was 61.7%, and negative predictive value was 65.3%. Receiver operating characteristic (ROC) curve revealed a significant sensitivity and specificity (ROC area = 0.664), (confidence interval [CI]: 0.530–0.781) (P < 0.023). The optimal cutoff value for PLR was ≥146, sensitivity was 60%, specificity was 83%, positive predictive value was 78%, and negative predictive value was 67%. ROC curve revealed a statistically significant sensitivity and specificity (ROC area = 0.726), (CI: 0.59–0.83) (P < 0.001). The optimal cutoff value for platelet was ≥284,000, sensitivity was 83%, specificity was 40%, positive predictive value was 58%, and negative predictive value was 70%. ROC curve revealed a significant sensitivity and specificity (ROC area = 0.65), (CI: 0.51–0.76) (P = 0.036). Conclusion: NLR, PLR, and thrombocyte count parameters can be useful in the process of diagnosing FMS. In addition, NLR, PLR, and MPV decreased in patients who received WCT.

Keywords: Fibromyalgia syndrome, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, wet cupping therapy

How to cite this article:
Aslaner H, Çalış HT, Karabaşc &, Benli AR. Hemogram parameters in fibromyalgia and effects of wet cupping therapy on hemogram parameters. World J Tradit Chin Med 2022;8:497-501
How to cite this URL:
Aslaner H, Çalış HT, Karabaşc &, Benli AR. Hemogram parameters in fibromyalgia and effects of wet cupping therapy on hemogram parameters. World J Tradit Chin Med [serial online] 2022 [cited 2022 Sep 9];8:497-501. Available from: https://www.wjtcm.net/text.asp?2022/8/4/497/337527   Introduction 

Fibromyalgia syndrome (FMS) is a chronical and painful disease accompanied by a group of symptoms such as widespread pain in musculoskeletal system, morning stiffness, sleep disorder, and irritable bowel syndrome.[1] FMS is more common in women.[2] In studies, its prevalence ranges from 4% to 8.8% and mean global prevalence is 2.7%.[3] Although pain is the main symptom in FMS painless symptoms can also affect the patients' quality of life.[4] The symptoms may range from mild to severe and affects the daily life of the patient in the worst conditions.[5] This may cause occupational and social limitations that are directly or indirectly associated with economic costs.[6] Its pathophysiology is still unclear. Several factors, especially environmental and genetic factors are involved. Traumatic causes, immunologic and hormonal factors, and viral infections play role.[7] There may also be immunologic changes causing inflammatory condition in fibromyalgia. Studies focusing on serum and plasma cytokine concentrations have revealed that IL-6, IL-8, IL-1 β, or tumor necrosis factor-alpha levels increase.[8],[9] Neutrophils play an active role in inflammation. There are some evidences revealing that neutrophil count in patients with FMS is higher than that of healthy population.[10] In addition, platelet distribution width (PDW) can be one of the markers in hematologic parameters of inflammatory activity in the pathogenesis of FMS according to some authors.[11] Neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are generally accepted as the markers of subclinical inflammation. NLR and MPV are simple, cheap, and easy inflammation markers and parameters that can be analyzed in all laboratories.[12]

Wet cupping therapy (WCT) is one of the complementary and traditional therapies that are still must be scientifically interpreted. WCT is known to be effective in the treatment of diseases with different etiologies such as hypertension, rheumatoid arthritis, and FMS. WCT decreases interstitial fluid pressure, inflammatory cytokines, and substance P. Due to these effects of WCT, it is a suitable and effective treatment method for FMS.

Improvement of symptoms in FMS and significant anti-inflammatory effects after WCT are evidences revealing that WCT is effective.[13]

This study aimed to assess hemogram parameters that are subclinical inflammatory markers in patients with FMS and observe how they were affected with WCT.

  Methods 

Study design and setting

The authors had no conflicts of interest to declare. This study was in compliance with all the procedures that are used in studies including human participants, ethical standards of institutional and/or national research committee and guidelines of 1964 Helsinki Declaration. Institutional approval of the study was obtained from the Local Health Authority and Ministry of Health and ethical approval from Kayseri City and Training and Research Hospitals (2020/17).

Our study was designed as a retrospective study including cases and controls. It included patients who were admitted to the Traditional and Complementary Medicine (T and CM) Center and who received WCT. Our study consisted of two groups: patient group included participants who were diagnosed with FMS and who received WCT and control group included healthy participants who received WCT within the concept of preventive medicine. Routine blood count is performed before WCT, in each sessions and 3 weeks after WCT for all patients and healthy individuals in the T and CM center.

Laboratory parameters were obtained before and 3 weeks after the first WCT in both groups. Regions where wet cupping are applied: head, trapezius, interscapular area, subscapular, processus mastoideus, paravertebral regions, lumbar vertebrae, and back of knee. WCT was performed with the same technique on all participants in both groups.

The data obtained were recorded in patient files. Those with high acute-phase reactants and a comorbid chronic disease were excluded from the study. Demographic data, clinical findings, and hemogram parameters of the patients were recorded from data processing system.

Study participants

A total of 69 individuals who were admitted to T and CM center of Kayseri Training and Research Hospital for WCT between January 1, 2016, and December 1, 2018, were reached. Individuals at the age of 18 years and above were included in the study. Five of the participants were excluded from the study as they had a comorbid chronic disease and four were excluded as their pre-WCT and post-WCT hemogram values could not be obtained. Patient group consisted of thirty patients and control group consisted of thirty healthy individuals.

Data screening process

Cases were assessed in two groups and the relationship of these cases in the groups with hemogram parameters was analyzed. Pre-WCT and post-WCT NLR, monocyte to lymphocyte ratio, MPV, PDW, and red cell distribution width (RDW) values of both patient and control groups were recorded. Complete blood count of the patients was performed with the complete blood count device called Sysmex XN-9000 series (Sysmexi Kobe, Japan). Neutrophil, lymphocyte, and platelet counts were measured according the method determined by the device and kit manufacturer. Leukocyte (103/μl), neutrophil (103/μl) and platelet (103/μl) counts and MPV (fL) values were obtained from hemogram analysis. NLR value was calculated by dividing the neutrophil count by the lymphocyte count and platelet-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count.

Statistical analysis

SPSS software version 22.0 (IBM Corp., Armonk, NY, USA) was used for the assessment of the data obtained. In data analysis, frequency, mean, median, standard deviation, minimum, and maximum values were determined as the descriptive data. The Chi-square test was used in the comparison of categorical data. In numerical data, Student's t-test was used in normally distributed two groups and Mann–Whitney U test was used in nonnormally distributed groups. In order to test the significance of the difference between the scores of the two measurement sets, the dependent sample t-test was used for the normally distributed numerical data, and the Wilcoxon t-test was used for those who did not comply with the normal distribution. Receiver operating characteristic (ROC) analysis was performed to determine the predictive values of hemogram parameters. P < 0.05 was accepted as the statistically significant result.

  Results 

The mean age of the participants including a patient group (54.3 ± 12.08) and control group (52.3 ± 11.9) was 54 ± 12.4, whereas 4 (6.7%) of the patients were male 56 (93.3%) were female and there were 27 (90%) women in the patient group and 29 (96.7%) women in the control group. The groups were similar in terms of age and gender. Main admission reason of the patient group was reported as widespread muscle pain in 12 patients (40%). While the groups were similar in terms of White blood cell count (WBC), neutrophil count and lymphocyte count platelet count was higher in the patient group (P = 0.046). NLR and PLR values were higher in the patient group (P = 0.029 and P = 0.003, respectively). MPV values were similar in the patient and control groups (P = 0.66). PDW and RDW values were similar between the groups (P = 0.157 and P = 0.813, respectively) [Table 1].

Considering that the participants had FMS, the optimal cutoff value for PLR was ≥1.62, sensitivity was 70%, specificity was 56%, positive predictive value was 61.7%, and negative predictive value was 65.3%. ROC curve revealed a significant sensitivity and specificity (ROC area = 0.664), (confidence interval [CI]: 0.530–0.781) (P < 0.023). The optimal cutoff value for PLR was ≥146, sensitivity was 60%, specificity was 83%, positive predictive value was 78%, and negative predictive value was 67%. ROC curve revealed a significant sensitivity and specificity (ROC area = 0.726), (CI: 0.59–0.83) (P < 0.001). The optimal cutoff value for platelet was ≥284,000, sensitivity was 83%, specificity was 40%, positive predictive value was 58%, and negative predictive value was 70%. ROC curve revealed a significant sensitivity and specificity (ROC area = 0.65), (CI: 0.51–0.76) (P = 0.036) [Figure 1] and [Table 2].

Figure 1: Receiver operating characteristic curve of neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, and thrombocyte levels

Click here to view

There was no significant change in WBC, neutrophil, lymphocyte, and thrombocyte levels of the patient group before and after the therapy (P = 0.284, P = 0.075, P = 0.559, and P = 0.553 respectively). NLR, PLR, and MPV values decreased after WCT (P = 0.012, P = 0.003, and P = 0.003, respectively) [Table 3]. PDW and RDW values were similar before and after the therapy (P = 0.915 and P = 0.126, respectively). WBC, neutrophil, lymphocyte, and thrombocyte values in the control group were similar before and after the therapy (P = 0.496, P = 0.901, P = 0.483, and P = 0.317, respectively). NLR, PLR, MPV, PDW, and RDW values were similar before and after WCT (P = 0.12, P = 0.09, P = 0.776, P = 0.925, and P = 0.130, respectively).

Table 3: Hemogram parameters in patients with fibromyalgia before and after the therapy

Click here to view

  Discussion 

In FMS, the disease is diagnosed with its own diagnostic criteria. It is known that immunologic and inflammatory events play a role in its etiopathogenesis. There is still no parameter revealing the prognosis of FMS. Some hemogram parameters can be the markers of possible inflammatory activity in pathogenesis of FMS and play role as markers in the early diagnosis of FMS.[10]

NLR and PLR are the parameters that are markers of inflammation.[12] In literature, there are many studies on variables of platelet volume in inflammation.[11] It is easy to reach these parameters with complete blood count that can be measured in all laboratories.

In the study comparing laboratory data of the controls and FMS patients, Karabaş reported that there was no difference between FMS group and control group in terms of lymphocyte count, platelet count, MPV, NLR, and PLR values.[14] Ata et al. RDW, MPV, NLR, PLR, WBC, neutrophil and lymphocyte values are similar. They reported that PDW was significantly lower in FMS, and Molina et al. reported that PDW was similar between groups in a study involving only women.[11],[15] In this study, WBC, neutrophil, lymphocyte, PDW, and RDW were similar between the patient and control group as in the literature. In the study on 70 FMS patients and 50 healthy volunteers, while İlgün et al. found NLR rates higher in the patient group although not significant, PLR rates were significantly high and they reported that PLR could be a subclinical inflammation marker.[16] Some authors stated that there were evidences revealing that there may be neuroendocrine-immune dysfunction in FMS.[8] MPV is a parameter which is the marker of thrombocyte function and activity. It is considered to play a role in immunologic and inflammatory events.[17] While Sayılır et al. reported that there was no significant difference when MPV levels of FMS and control group were compared Haliloglu et al. stated that MPV levels significantly increased in FMS.[18] In this study, while MPV was in similar levels in FMS and control group NLR and PLR values and platelet count were significantly high compared to the control group. The reason for this may be that NLR, PLR, and platelet count are more sensitive in FMS than other hematological parameters. It is hard to diagnose FMS. In some studies, cutoff and predictive values were determined for hemogram parameters in FMS. Karataş and Gündüz reported that cutoff values were 120.3 for PLR and 1.76 for NLR and the areas under the curve were 0.642 and 0.623 for PLR and NLR.[19] Platelet count and PLR value of female participants with FMS were higher than those of healthy women. In a different publication, while cutoff values were reported as >212,000 for platelet count and >100 for PLR the areas under the curve were 709 and 712.[15] The areas under the curve and cutoff values for PLR, NLR, and platelet count in our study were similar with the values in literature. Similarity of our data with those in studies suggests that NLR and PLR values and platelet count can be subclinical inflammation markers in FMS. As especially its area under the curve is the highest PLR is considered to be one of the parameters that can help diagnosis in FMS.

Treatment methods in FMS include exercises, cognitive behavioral programs, physical therapy methods, acupuncture, hydrotherapy, massage and warm water baths, WCT, and pharmacological therapy.[20] In a study in which participants were divided into three groups as cupping therapy, sham cupping, or usual care, cupping was applied to the upper and lower back five times for 2 weeks, then pain intensity was measured on day 18, and significantly less pain was reported after cupping compared to normal care.(difference ‒12.4; 95% CI: ‒18.9; ‒5.9, P < 0.001), but found no difference with placebo (sham cupping) (difference − 3.0; 95% CI: −9.9, 3.9, P = 0.396). Further effects were found for quality of life compared to usual care.[21] WCT decreases the severity of pain in FMS and increases the quality of life.[22] As there are limited number of studies on the mechanisms of action of WCT several hypotheses have been asserted. Its neural, hematologic, immunologic, and metabolic effects are mentioned. Excretion of proinflammatory substances, inflammation cells, and harmful chemical and biological substances becomes easy after WCT.[23]

In the study by Mahdavi et al., while neutrophil count significantly decreased 2 weeks after WCT lymphocyte count significantly increased. They revealed the decrease in WBC although it was not statistically significant.[24] In the study by Al-Kazazz et al., basal neutrophil count in hemogram values measured before WCT and 2 weeks after WCT decreased, lymphocyte values increased and although not significant, NLR decreased.[25] Abdullah et al. did not record a significant change in pre-WCT and post-WCT platelet count and RDW in healthy individuals.[26] The study was performed with a patient group in which an inflammation could accompany, which may have affected that result. No similar study in which the relationship between WCT and MPV was assessed was found in literature. Platelet count often changes during inflammation and the change in volume occurs before the change in count.[27] While thrombocyte count did not change in this study significant decrease in MPV values may be for that reason. WCT combined with conventional therapy can improve the clinical condition of inflammatory diseases. Improvement rate of clinical and laboratory cellular and immunological parameters is significantly higher in the therapy combined with WCT compared to the conventional therapy.[28] In this study, NLR, PLR, MPV rate, and thrombocyte count significantly decreased in the patient group after WCT, which is consistent with findings in the literature. This suggests that WCT decreased inflammation.

Limitations of our study can be as follows: The number of patients was low; clinical parameters of the disease could not be assessed; and it was a retrospective study. There were no FMS patients in the records who did not receive any treatment. All FMS patients had either medical treatment or WCT if there was a control group of FMS patients more effective for this study. We think further studies including higher number of patients and clinical data are needed.

  Conclusion 

NLR, PLR, and thrombocyte count that are subclinical inflammation markers in FMS were high in this study. NLR, PLR, and thrombocyte count parameters can be useful in the process of diagnosing FMS. In addition, NLR, PLR, and MPV decreased in patients who received WCT. This study aimed to reveal the effect of WCT of inflammation. WCT can be used as a complementary therapy in rheumatic diseases with inflammation and diseases accompanied with widespread muscle pain.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

  References 
1.Wolfe F, Walitt B, Perrot S, Rasker JJ, Häuser W. Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias. PLoS One 2018;13:e0203755.  
    2.Yunus MB. The role of gender in fibromyalgia syndrome. Curr Rheumatol Rep 2001;3:128-34.  
    3.Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep 2013;17:356.  
    4.Bernard AL, Prince A, Edsall P. Quality of life issues for fibromyalgia patients. Arthritis Care Res 2000;13:42-50.  
    5.Lempp HK, Hatch SL, Carville SF, Choy EH. Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: A qualitative study. BMC Musculoskelet Disord 2009;10:124.  
    6.Lacasse A, Bourgault P, Choinière M. Fibromyalgia-related costs and loss of productivity: A substantial societal burden. BMC Musculoskelet Disord 2016;17:168.  
    7.Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Häuser W, Fluß E, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 2017;76:318-28.  
    8.Mendieta D, De la Cruz-Aguilera DL, Barrera-Villalpando MI, Becerril-Villanueva E, Arreola R, Hernández-Ferreira E, et al. IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol 2016;290:22-5.  
    9.Franks HM, Cronan TA, Santoro MS, Roesch SC, Devos-Comby L, Wooldridge JS, et al. Is coping goodness-of-fit related to depression and mood disturbance in women with fibromyalgia syndrome? J Musculoskelet Pain 2012;20:183-93.  
    10.Geiss A, Rohleder N, Anton F. Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia. Psychoneuroendocrinology 2012;37:671-84.  
    11.Emre A, Düzenli T. Fibromiyalji tanısında inflamatuar bir belirteç: Platelet dağılım genişliği. Platelet distribution width as a novel inflammatory marker for fibromyalgia. Bozok Tıp Derg 2019;9:73-7.  
    12.Aktürk S, Büyükavcı R. Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia. Clin Rheumatol 2017;36:1885-9.  
    13.El Sayed SM, Mahmoud HS, Nabo MMH. Methods of wet cupping therapy (Al-Hijamah): in light of modern medicine and prophetic medicine. Altern Integr Med 2013;2:1-16.  
    14.Karabaş Ç. Fibromyalji hastalarında nötrofil/lenfosit oranı, platelet/lenfosit oranı ve ortalama trombosit hacminin değerlendirilmesi. Evaluation of neutrophil/lymphocyteratio, platelet/lymphocyte ratio and mean platelet volume in patients of fibromyalgia J Anatol Med Res 2018;3:1-10.  
    15.Molina F, Del Moral ML, La Rubia M, Blanco S, Carmona R, Rus A. Are patients with fibromyalgia in a prothrombotic state? Biol Res Nurs 2019;21:224-30.  
    16.İlgün E, Akyürek Ö, Kalkan AO, Demir F, Demirayak M, Bilgi M. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in fibromyalgia. Eur J Gen Med 2016;13:100-4.  
    17.Bath P, Algert C, Chapman N, Neal B; PROGRESS Collaborative Group. Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 2004;35:622-6.  
    18.Sayılır S. Remarkable hematological laboratory findings in patients with fibromyalgia syndrome. Turk J Osteoporos 2016;22:121-4.  
    19.Karataş G, Gündüz R. The significance of inflammation markers in complete blood count in patients with fibromyalgia. Med Sci Discov 2020;7:364-7.  
    20.Valentini E, Fetter E, Orbell S. Treatment preferences in fibromyalgia patients: A cross-sectional web-based survey. Eur J Pain 2020;24:1290-300.  
    21.Lauche R, Spitzer J, Schwahn B, Ostermann T, Bernardy K, Cramer H, et al. Efficacy of cupping therapy in patients with the fibromyalgia syndrome – A randomised placebo controlled trial. Sci Rep 2016;6:37316.  
    22.Cao H, Hu H, Colagiuri B, Liu J. Medicinal cupping therapy in 30 patients with fibromyalgia: A case series observation. Forsch Komplementmed 2011;18:122-6.  
    23.Okumuş M. Cupping therapy and hijamah. Ankara Med J. 2016;16:370-82.  
    24.Mahdavi MR, Ghazanfari T, Aghajani M, Danyali F, Naseri M. Evaluation of the effects of traditional cupping on the biochemical, hematological and immunological factors of human venous blood. A Comp of Essays on Altern Ther Croatia: InTec 2012;6:67-88.   
    25.Al-Kazazz FF, Abdulsattar SA, Mohammed K. Study effect of wet cupping on hemato-logical parameters and inflammatory proteins of healthy Iraqi men. Am J Phytomed Clin Ther 2014;2:644-9.  
    26.Abdullah SA, Najib MN, Dali AF, Sulaiman S, editors. Malay cupping therapy: A haematological analysis pilot study. In: Regional Conference on Science, Technology and Social Sciences (RCSTSS 2014). Singapore: Springer; 2016.  
    27.Haliloğlu S, Carlioglu A, Sahiner E, Karaaslan Y, Kosar A. Mean platelet volume in patients with fibromyalgia. Z Rheumatol 2014;73:742-5.  
    28.Ahmed SM, Madbouly NH, Maklad SS, Abu-Shady EA. Immunomodulatory effects of blood letting cupping therapy in patients with rheumatoid arthritis. Egypt J Immunol 2005;12:39-51.  
    
  [Figure 1]
 
 
  [Table 1], [Table 2], [Table 3]