Abstract
Behçet's syndrome (BS) is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and mean platelet volume (MPV) in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC), neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p < 0.001). Lymphocyte counts and MPVs of the BS group were not statistically different from healthy controls (all p > 0.05). In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively). We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies.
Keywords: Behçet's syndrome, MPV, NLR, PLR
Introduction
Behçet's syndrome (BS) is an inflammatory vasculitis characterized by mucocutaneous and joint manifestations, recurrent thrombophlebitis/thrombosis or deep vein thrombosis, and eye and central nervous system involvement [1]. BS is classified among vasculitides of unknown etiology and pathogenesis. BS is associated with chronic inflammation and endothelial dysfunction [2]. Laboratory tests are not useful and diagnosis is based upon clinical manifestations. Blood parameters such as neutrophils and platelet activities are increased in BS [[2], [3]].
High neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) values indicate increased inflammation [[4], [5], [6], [7]]. NLR and PLR in peripheral blood are easy systemic inflammatory responses. NLR possesses diagnostic value in certain pathologies characterized by systemic or local inflammatory response such as diabetes mellitus, coronary artery disease, ulcerative colitis, and inflammatory arthritis [[8], [9]]. PLR is a new biomarker indicating inflammation [10]. PLR is associated with bad prognosis in patients, with a key role in atherosclerosis and atherothrombosis in peripheral arterial occlusive disease patients [2]. Furthermore, PLR is thought to be a more sensitive marker and also assumed to be a prognostic factor in many malignancies [11]. Mean platelet volume (MPV) is another marker that shows platelet count and activity. The MPV has been shown to be associated with inflammation and inflammation severity [12].
According to the literature, there are only a few studies examining the relationship between NLR, MPV, and BS. But there is no study examining the relationship between PLR and BS. In this study, we aimed to compare the levels of MPV, NLR, and PLR in patients with BS and healthy controls. Also, we evaluated the association between disease activity and MPV, NLR, and PLR as well as other laboratory parameters.
Methods
Study population
The study was conducted retrospectively in the Dermatology and Venereology Department of Akdeniz University, Antalya, Turkey. The data were extracted from medical records of patients between January 2014 and December 2014. The study included 254 patients with BS. BS was based on the criteria of the International Study Group for Behçet's Syndrome (ICBS) [13]. The study included 173 non‐BS patients diagnosed with pruritus in the dermatology outpatient clinic. These patients were age‐ and sex‐matched to the cases. They did not have any dermatologic or systemic disorder. First, laboratory test results of the patients at first diagnosis with BS were recorded during the examination of the medical records of the patients. The patients were not taking any medication when the laboratory tests were performed. Through making phone calls and examination of the medical records of the patients, it was determined that: 52 patients did not take any treatment because of remission or other causes; 69 patients only used colchicine; and the remaining 133 patients took single, binary, or triple combined immunosuppressant treatment. Age, sex, age of onset, duration of disease, follow‐up time, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, T lymphocyte counts, and human leukocyte antigen (HLA)‐B51 positivity of the patients were recorded.
Patients and control participants who had other skin diseases, inflammatory or infectious diseases, diabetes mellitus, or cardiovascular, liver, or kidney diseases were excluded from the study. Patients with BS who received colchium, azothiopurin, steroids, and other immune suppressor drugs during the previous 6 months were also excluded.
Measurements
Total white blood cell (WBC) count, neutrophil, and lymphocyte differentials were determined using an automated blood cell counter (Siemens Advia 2120 analyzer, Erlangen, Germany). Complete blood counts were measured by the method of laser‐based flow cytometric impedance (BN2 Siemens). Severity score was calculated as the sum of one point for each of the mild symptoms (oral aphtosis, genital ulcer, erythema nodosum, papulopustular lesions, folliculitis, leucocytoclastic vasculitis, arthralgia, recurrent headaches, epididymitis, chronic diarrhea, chronic recurrent abdominal pain, colic, pleuritic pain, and superficial vein thrombosis). They received 2 points for each moderate symptom (arthritis, deep vein thrombosis of the legs, anterior uveitis, and gastrointestinal bleeding), and 3 points for each severe disease manifestation (posterior/pan uveitis, retinal vasculitis, arterial thrombosis or aneurysms, major vein thrombosis, neuro‐Behçet, and bowel perforation). Categorization of the severity of the disease was not done according to the total score. The patient was categorized in the severe group, even if the patient experienced the severe manifestations of the disease once in their lifetime. If there were no severe findings, whereas one of the moderate manifestations was detected at a time, the patient was categorized in the moderate group. Lastly, the patients who did not have moderate or severe manifestations of the disease and had BS with only mild manifestations were considered in the mild group (Figure 1) [14]. Total scoring was only used in the correlation analysis. Scoring of the disease and blood sampling were not done simultaneously. For the blood counts, first blood test results of the patients when they had been just diagnosed with BS (e.g., 10 year old hematologic test results of the patient) were considered. But for the disease severity scale, every symptom/attack that the patient had experienced throughout his/her life was taken into consideration. The patients that were on any drugs during the blood sampling were left out of the study.
Figure 1.
Krause's assessment of Behçet's syndrome activity (Krause, 1999).
Statistical analysis
Analyses were performed using SPSS software (version 20.0, SPSS Inc., Chicago, IL, USA). Continuous data were presented as mean ± standard deviation (SD). Differences in the continuous variables between groups were determined by Student t test or the Mann–Whitney U test, for variables with or without normal distribution, respectively. To test the normal distribution, the Kolmogorov–Smirnov test was used. Categorical variables were summarized as percentages and compared with the χ2 test. Because all continuous variables are non‐normal, the Spearman correlation coefficient was computed to examine the association between two continuous variables. Because some variables are non‐normal and some variables are normal the Kruskal–Wallis test and one way analysis of variance test were used to compare the three severity groups. Logistic regression analysis was also conducted to assess relationships; results are presented as odds ratios (OR) and 95% confidence intervals. Input variables of binary logistic regression were NLR, PLR, and sex. Statistical significance was defined as p < 0.05.
Results
Our study sample comprised 254 patients with BS and 173 healthy controls. Age and sex were similar between the groups. The comparisons among the healthy and patients groups of demographic features and laboratory findings are shown in Table 1. WBC, neutrophil, platelet, NLR, and PLR were statistically significant in patients with BS when compared with healthy controls (all p < 0.001; Table 1). One hundred and twenty of them were in the mild group, 66 of them in the moderate group and 68 of them were in the severe group. In the BS group, PLR and MPV were significantly different among the three severity groups. (p = 0.037 and p = 0.016, respectively; Table 2). There were no statistically significant differences between PLR and MPV of the severe and moderate groups and the moderate and mild groups. PLR and MPV of the severe group were significantly higher than the PLR and MPV of the mild group (p = 0.032, p = 0.015, respectively; independent‐samples Mann–Whitney U test). Otherwise we showed that NLR, PLR, and MPV were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS (p ˃ 0.05; Table 3). According to Krause's scoring system, the mean severity scores of the patients with BS were detected as 5.28 ± 0.13. There were no correlation between the severity score of BS and the laboratory parameters (p ˃ 0.05). Multivariate analysis found that NLR was an independent predictor for BS (p < 0.001, OR = 2.535; Table 4).
Table 1.
The demographic and laboratory characteristics of the patients with Behçet's syndrome and control groups.
| Behçet's syndrome (n = 254) | Control (n = 173) | p | |
|---|---|---|---|
| Age (y) | 42.83 ± 10.49 | 41.06 ± 12.31 | 0.150 |
| Male/female | 140/114 | 99/74 | 0.667 |
| WBC | 8.48 ± 1.72 | 6.69 ± 1.51 | < 0.001 |
| Neutrophil (103/mL) | 5.72 ± 1.74 | 3.80 ± 1.20 | < 0.001 |
| Lymphocyte (103/mL) | 2.01 ± 0.64 | 2.17 ± 0.91 | 0.125 |
| Platelet (103/mL) | 287.36 ± 70.89 | 253.61 ± 67.37 | < 0.001 |
| NLR | 3.37 ± 2.74 | 1.95 ± 1.21 | < 0.001 |
| PLR | 157.69 ± 73.59 | 127.75 ± 46.02 | < 0.001 |
| MPV | 8.69 ± 1.03 | 8.70 ± 0.99 | 0.305 |
Data are presented as mean ± standard deviation.
MPV = mean platelet volume; NLR = neutrophil/lymphocyte ratio; PLR = platelet/lymphocyte ratio; WBC = white blood cell.
Table 2.
Demographic and clinical characteristics of different severity groups in patients with Behçet's syndrome.
| Mild disease (n = 120) | Moderate disease (n = 66) | Severe disease (n = 68) | p | |
|---|---|---|---|---|
| Age (y) | 42.90 ± 9.94 | 44.62 ± 12.27 | 40.99 ± 9.30 | 0.689 |
| Male/female | 57/63 | 36/30 | 47/21 | 0.016 |
| Follow up time (y) | 5.51 ± 3.38 | 6.68 ± 3.32 | 6.13 ± 3.59 | 0.067 |
| Duration of disease (y) | 6.94 ± 5.92 | 8.91 ± 5.99 | 8.51 ± 5.81 | 0.006 |
| Family history (+) | 18/102 | 10/56 | 8/60 | 0.801 |
| Current smokers | 19/101 | 14/52 | 44/24 | < 0.001 |
| HLA B51 (+) | 20/100 | 21/45 | 34/34 | < 0.001 |
| Hematuria (+) | 19/101 | 10/56 | 16/52 | 0.339 |
| Proteinuria (+) | 9/111 | 3/63 | 6/62 | NA a |
| WBC | 8.45 ± 1.68 | 8.38 ± 1.67 | 8.63 ± 2.33 | 0.590 |
| Neutrophils (103/mL) | 5.65 ± 1.64 | 5.64 ± 1.89 | 5.92 ± 0.21 | 0.051 |
| Lymphocytes (103/mL) | 2.06 ± 0.54 | 2.00 ± 0.63 | 1.99 ± 0.68 | 0.080 |
| Platelets (103/mL) | 287.34 ± 68.65 | 281.66 ± 62.65 | 292.94 ± 82.06 | 0.205 |
| NLR | 3.03 ± 1.07 | 3.50 ± 1.12 | 3.82 ± 1.41 | 0.150 |
| PLR | 150.28 ± 71.74 | 156.61 ± 69.23 | 171.82 ± 79.75 | 0.037 |
| MPV | 8.59 ± 0.96 | 8.61 ± 1.10 | 8.92 ± 0.13 | 0.016 |
Data are presented as mean ± standard deviation.
MPV = mean platelet volume; NA = not applicable; NLR = neutrophil/lymphocyte ratio; PLR = platelet/lymphocyte ratio; WBC = white blood cell.
Two cells (33.3%) have an expected count < 5. The minimum expected count is 4.68.
Table 3.
Neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and mean platelet volume values in cases of different system involvements.
| NLR | PLR | MPV | ||
|---|---|---|---|---|
| Joint involvement | + | 3.30 ± 2.82 | 155.34 ± 66.91 | 8.62 ± 0.99 |
| − | 3.48 ± 2.62 | 161.28 ± 84.06 | 8.81 ± 1.10 | |
| p | 0.205 | 0.646 | 0.250 | |
| Eye involvement | + | 3.81 ± 3.70 | 166.27 ± 83.11 | 8.79 ± 1.06 |
| − | 3.11 ± 1.97 | 152.60 ± 67.23 | 8.63 ± 1.02 | |
| p | 0.241 | 0.225 | 0.078 | |
| CNS involvement | + | 3.69 ± 2.01 | 155.40 ± 45.85 | 8.57 ± 1.45 |
| − | 3.35 ± 2.76 | 157.78 ± 74.57 | 8.69 ± 1.02 | |
| p | 0.250 | 0.537 | 0.765 | |
| GIS involvement | + | 3.49 ± 1.53 | 165.16 ± 59.64 | 8.75 ± 1.16 |
| − | 3.36 ± 2.76 | 157.51 ± 73.99 | 8.69 ± 1.03 | |
| p | 0.454 | 0.621 | 0.518 | |
| Arterial/venous involvement | + | 2.73 ± 1.86 | 100.73 ± 40.98 | 8.75 ± 1.34 |
| − | 3.37 ± 2.75 | 158.02 ± 73.79 | 8.69 ± 1.04 | |
| p | 0.750 | 0.153 | 0.911 | |
| Thrombo phlebitis | + | 3.44 ± 1.52 | 153.39 ± 52.74 | 8.75 ± 1.23 |
| − | 3.36 ± 2.85 | 158.03 ± 73.75 | 8.68 ± 1.03 | |
| p | 0.165 | 0.751 | 0.591 | |
Data are presented as mean ± standard deviation.
CNS = central nervous system; GIS = gastrointestinal system; MPV = mean platelet volume; NLR = neutrophil/lymphocyte ratio; PLR = platelet/lymphocyte ratio.
Table 4.
Binary forward stepwise logistic regression analysis of variables related to Behçet's Syndrome.
| 95% CI | ||||||
|---|---|---|---|---|---|---|
| p | OR | Lower | Upper | Nagelkerk R2 | Cox–Snell R2 | |
| NLR | <0.001 | 2.535 | 1.878 | 3.301 | ||
| PLR | 0.323 | 0.998 | 0.992 | 1.003 | ||
| MPV | 0.315 | 0.898 | 0.729 | 1.109 | 0.219 | 0.162 |
CI = confidence interval; MPV = mean platelet volume; NLR = neutrophil/lymphocyte ratio; OR = odds ratio; PLR = platelet/lymphocyte ratio.
Discussion
The marked findings of the present study were that NLR, PLR, WBC, neutrophils, and platelets were different in the patients of BS and healthy controls. In addition, PLR and MPV were significantly higher in patients with severe BS compared with mild BS. We showed that NLR was an associated factor for the presence of BS.
Some studies claimed that NLR is a new biomarker which indicates the presence of inflammation in literature. Various studies have demonstrated the correlation between NLR and the severity of some systemic inflammatory diseases as well as coronary artery disease [4]. In the literature, Balta et al. [15] showed that the NLR, C‐reactive protein (CRP), and the WBC levels were higher in patients with BS than controls. In addition, NLR was higher in patients with active BS than in those with inactive BS. Öztürk et al. [16] investigated the correlation between NLR and inflammatory activity in BS. They showed that NLR levels were significantly higher in active patients with BS than in inactive patients. Similarly, different studies demonstrated NLR as a useful marker for indicating the presence and prognosis of inflammatory diseases and malignancies [[8], [18]]. Also in our study, only NLR was detected as an independent decisive factor among the laboratory parameters in BS according to the multivariate analysis. Based on this data, we believe that NLR can be a useful laboratory parameter in the diagnosis of BS. Similarly to the literature, we found that the mean NLR values of the patient group were significantly higher than the mean NLR values of the control group.
PLR is a novel biomarker which can demonstrate the presence and severity of inflammation [10]. Kokcu et al. [17] reported that the NLR, platelet count, and the PLR increased with the increasing stage of ovarian cancer. Also, they claimed that the PLR was an independent prognostic factor related to the stage of epithelial ovarian cancer. Racz et al. [18] showed that high PLR was associated with reduced recurrence‐free survival in patients with gastrointestinal stromal tumors. Similarly, Azab et al. [7] reported the presence of a correlation between increased PLR and long‐term mortality in patients presented with non‐ST segment elevation myocardial infarction. In another study, increased PLRs were found to be associated with non‐dipper state in hypertensive patients [19]. This is the first study that showed the association between PLR and a novel marker of the presence and severity of BS.
MPV has been widely used as a new marker of inflammation. Ekiz et al. [20] showed that the patients with BS and recurrent aphtous stomatitis had significantly higher MPV and erythrocyte sedimentation rate levels compared with controls. Similarly, Yazici et al. [21] found that MPV was significantly higher in patients with ankylosing spondyloarthritis and rheumatoid arthritis, and MPV reflected the activity of both diseases. Nevertheless, we did not find a significant difference in MPV levels among the patients with BS and healthy controls. Kisacik et al. [22] showed that high grade inflammation was associated with a decrease in MPV levels in the other chronic inflammatory diseases such as rheumatoid arthritis and ankylosing spondyloarthritis. Similar to this study, Açıkgöz et al. [23] demonstrated that any difference between MPV levels and disease activity was not found. On the contrary, we found a significant difference in MPV levels of different BS severity groups. Platelets are essential in hemostasis and the formation of both arterial [24] and venous thrombosis [25]. Platelet count is also a marker of host systemic inflammation [10]. The platelet count can be determined by both inherited and environmental factors [26]. In different studies, abnormal increases in platelet counts have been associated with the development of atherosclerosis, atherosclerotic heart disease, and major cardiovascular events [27]. Jensvoll et al. [28] claimed that precancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer‐free individuals. Also, they showed that the combination of platelet and leukocyte counts in the upper quintiles had a synergistic effect and yielded a threefold increased risk of venous thromboembolism.
Neutrophils are actively involved in systemic and local inflammatory responses by releasing proinflammatory elements [9]. Significant roles of leukocytes and particularly neutrophils in atherogenesis and atherothrombosis are already recognized [29]. Neutrophils are the main agents responsible for tissue damage and have an intrinsic hyperactivation in BS patients [29]. Our study demonstrates that the platelet, neutrophil, and leukocyte counts are higher in patients with BS compared to healthy controls. Otherwise, we found that leukocyte and platelet counts were not associated with venous and arterial thrombosis or other systems involvement.
There are some limitations of our study. First, this is a retrospective study. Because this study was not a cohort study, the findings did not offer convincing evidence to demonstrate that PLR and MPV might be helpful as a biomarker to “predict” the severity of BS. Second, we used spot NLR, PLR, and MPV values for our analysis, rather than follow‐up values. Because this study was retrospective, we couldn't use Behçet's Syndrome Current Activity Form (BSCAF) for assessing disease activity. Third, we did not perform an analysis of the prognostic value of NLR, PLR, and MPV in BS.
In light of our findings, NLR and PLR might be associated with the presence and severity of BS. We suggest that NLR can be considered to be a diagnostic criterion of Behçet's syndrome given the support of the findings from larger prospective studies.
Conflicts of interest: All authors declare no conflicts of interest.
References
- [1]. Emmi G., Silvestri E., Squatrito D., D'Elios M.M., Ciucciarelli L., Prisco D., et al. Behçet's syndrome pathophysiology and potential therapeutic targets. Int Emerg Med. 2014; 9: 257–265. [DOI] [PubMed] [Google Scholar]
- [2]. Macey M., Hagi‐Pavli E., Stewart J., Wallace G.R., Stanford M., Shirlaw P., et al. Age, gender and disease related platelet and neutrophil activation ex vivo in whole blood samples from patients with Behçet's disease. Rheumatology. 2011; 50: 1849–1859. [DOI] [PubMed] [Google Scholar]
- [3]. Akar S., Ozcan M.A., Ateş H., Gürler O., Alacacioglu I., Ozsan G.H., et al. Circulated activated platelets and increased platelet reactivity in patients with Behçet's disease. Clin Appl Thromb Hemost. 2006; 12: 451–457. [DOI] [PubMed] [Google Scholar]
- [4]. Sönmez O., Ertaş G., Bacaksız A., Tasal A., Erdoğan E., Asoğlu E., et al. Relation of neutrophil‐to‐lymphocyte ratio with the presence and complexity of coronary artery disease, An observational study [Koroner arter hastalığı varlığı ve karmaşıklığı ile nötrofil lenfosit oranı ilişkisi]. Anadolu Kardiyoloji Dergisi. 2013; 13: 662–667, [in Turkish]. [DOI] [PubMed] [Google Scholar]
- [5]. Tsiara S., Elisaf M., Jagroop I.A., Mikhailidis D.P.. Platelets as predictor of vascular risk, is there a practical index of platelet activity?. Clin Appl Thromb Hemost. 2003; 9: 177–190. [DOI] [PubMed] [Google Scholar]
- [6]. Azab B., Daoud J., Naeem F.B., Nasr R., Ross J., Ghimire P., et al. Neutrophil‐to‐lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3‐year follow‐up study). Ren Fail. 2012; 34: 571–576. [DOI] [PubMed] [Google Scholar]
- [7]. Azab B., Shah N., Akerman M., McGinn J.T. Jr.. Value of platelet/lymphocyte ratio as a predictor of all‐cause mortality after non‐ST elevation myocardial infarction. J Thromb Thrombolysis. 2012; 34: 326–334. [DOI] [PubMed] [Google Scholar]
- [8]. Celikbilek M., Dogan S., Ozbakir O., Zararsiz G., Kücük H., Gürsoy S., et al. Neutrophil‐lymphocyte ratio as a predictor of disease severity in ulcerative colitis. J Clin Lab Anal. 2013; 27: 72–76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9]. Tousoulis D., Antoniades C., Koumallos N., Stefanadis C.. Proinflammatory cytokines in acute coronary syndromes, from bench to bedside. Cytokine Growth Factor Rev. 2006; 17: 225–233. [DOI] [PubMed] [Google Scholar]
- [10]. Koseoglu H.I., Altunkas F., Doruk S., Etikan I., Demir O., Kanbay A.. Platelet–lymphocyte ratio is an independent predictor for cardiovascular disease in obstructive sleep apnea syndrome. J Thromb Thrombolysis. 2015; 39: 179–185. [DOI] [PubMed] [Google Scholar]
- [11]. Proctor M.J., Morrison D.S., Talwar D., Balmer S.M., Fletcher C.D., O'Reilly D.S., et al. A comparison of inflammation‐based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. Eur J Cancer. 2011; 47: 2633–2641. [DOI] [PubMed] [Google Scholar]
- [12]. Ryu H.J., Lee M.K., Lee K.H., Seo M.R., Choi H.J., Baek H.J.. Mean platelet volume is associated with Behçet's disease activity. Ann Rheum Dis. 2014; 73: 996–997. [Google Scholar]
- [13]. Davatchi F., Assaad‐Khalil S., Calamia K.T., Crook J.E., Sadeghi‐Abdollahi B., Schirmer M., et al. The International Criteria for Behçet's Disease (ICBS), a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. 2014; 28: 338–347. [DOI] [PubMed] [Google Scholar]
- [14]. Krause I., Rosen Y., Kaplan I., Milo G., Guedj D., Molad Y., et al. Recurrent aphthous stomatitis in Behçet's disease, clinical features and correlation with systemic disease expression and severity. J Oral Pathol Med. 1999; 28: 193–196. [DOI] [PubMed] [Google Scholar]
- [15]. Balta S., Balta I., Öztürk C., Demirkol S., Koryurek O.M., Cakar M., et al. Neutrophil lymphocyte ratio in patients with Behçet's disease and its association with carotid intima–media thickness. Am J Card. 2014; 113: 7–11.24169013 [Google Scholar]
- [16]. Öztürk C., Balta S., Balta I., Demirkol S., Celik T., Turker T., et al. Neutrophil–lymphocyte ratio and carotid‐intima media thickness in patients with Behçet disease without cardiovascular involvement. Angiology. 2015; 66: 291–296. [DOI] [PubMed] [Google Scholar]
- [17]. Kokcu A., Kurtoglu E., Celik H., Tosun M., Malatyalioglu E., Ozdemir A.Z.. May the platelet to lymphocyte ratio be a prognostic factor for epithelial ovarian cancer?. Asian Pac J Cancer Prev. 2014; 15: 9781–9784. [DOI] [PubMed] [Google Scholar]
- [18]. Racz J.M., Cleghorn M.C., Jimenez M.C., Atenafu E.G., Jackson T.D., Okrainec A., et al. Predictive ability of blood neutrophil‐to‐lymphocyte and platelet‐to‐lymphocyte ratios in gastrointestinal stromal tumors. Ann Surg Oncol. 2014; 22: 2343–2350. [DOI] [PubMed] [Google Scholar]
- [19]. Sunbul M., Gerin F., Durmus E., Kivrak T., Sari I., Tigen K., et al. Neutrophil to lymphocyte and platelet to lymphocyte ratio in patients with dipper versus non‐dipper hypertension. Clin Exp Hypertens. 2014; 36: 217–221. [DOI] [PubMed] [Google Scholar]
- [20]. Ekiz O., Balta I., Sen B.B., Rifaioglu E.N., Ergin C., Balta S., et al. Mean platelet volume in recurrent aphthous stomatitis and Behçet disease. Angiology. 2014; 65: 161–165. [DOI] [PubMed] [Google Scholar]
- [21]. Yazici S., Yazici M., Erer B., Erer B., Calik Y., Bulur S., et al. The platelet functions in patients with ankylosing spondylitis, anti‐TNF‐alpha therapy decreases the mean platelet volume and platelet mass. Platelets. 2010; 21: 126–131. [DOI] [PubMed] [Google Scholar]
- [22]. Kisacik B., Tufan A., Kalyoncu U., Karadag O., Akdogan A., Ozturk M.A., et al. Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis. Joint Bone Spine. 2008; 75: 291–294. [DOI] [PubMed] [Google Scholar]
- [23]. Acikgoz N., Karincaoglu Y., Ermis N., Yagmur J., Atas H., Kurtoglu E., et al. Increased mean platelet volume in Behçet's disease with thrombotic tendency. Tohoku J Exp Med. 2010; 221: 119–123. [DOI] [PubMed] [Google Scholar]
- [24]. Davı G., Patrono C.. Platelet activation and atherothrombosis. New Engl J Med. 2007; 357: 2482–2494. [DOI] [PubMed] [Google Scholar]
- [25]. von Brühl M.L., Stark K., Steinhart A., Chandraratne S., Konrad I., Lorenz M., et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo . J Exp Med. 2012; 209: 819–835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26]. Santimone I., Di Castelnuovo A., De Curtis A., Spinelli M., Cugino D., Gianfagna F., et al. White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population, results from the MOLI‐SANI project. Haematologica. 2011; 96: 1180–1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [27]. Thaulow E., Erikssen J., Sandvik L., Stormorken H., Cohn P.F.. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation. 1991; 84: 613–617. [DOI] [PubMed] [Google Scholar]
- [28]. Jensvoll H., Blix K., Brækkan S.K., Hansen J.B.. Platelet count measured prior to cancer development is a risk factor for future symptomatic venous thromboembolism; the Tromsø Study. PLoS One. 2014; 18: e92011.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29]. Horne B.D., Anderson J.L., John J.M., Weaver A., Bair T.L., Jensen K.R., et al. Which white blood cell subtypes predict increased cardiovascular risk?. J Am Coll Cardiol. 2005; 45: 1638–1643. [DOI] [PubMed] [Google Scholar]