Skip to main content
Download PDF

Thrombocytosis in patients with spondyloarthritis: a case–control study

BMC Musculoskeletal Disorders volume 24, Article number: 195 (2023) Cite this article

Abstract

Objective

This study aimed to investigate the clinical and laboratory as well as radiological features of spondyloarthritis (SpA) patients with thrombocytosis and to explore risk factor for thrombocytosis in SpA patients and to assess the effect of antitumor necrosis factor-α (anti-TNF-α) therapy on platelet count in SpA patients with thrombocytosis.

Methods

A total of 145 patients with SpA were included in this study, and non-thrombocytosis was identified in 76 patients while thrombocytosis was found in 69 patients, 38 out of the 69 patients received anti-TNF-α therapy. Logistic regression analysis was performed to investigate risk factors that associated with thrombocytosis. The platelet count of patients in the thrombocytosis group treated with anti-TNF-α therapy on week 0, week 6 and week 12 were collected and compared with conventional therapy group.

Results

The proportion of hip involvement (60.86% vs 36.84%, p = 0.004), bath ankylosing spondylitis disease activity index score (4.24 ± 0.55 vs 3.69 ± 0.67, p < 0.001), erythrocyte sedimentation rate (62.22 ± 41.97 mm/hour vs 27.00 ± 25.93 mm/hour, p < 0.001), C-reactive protein (53.45 ± 47.45 mg/L vs 18.91 ± 31.09 mg/L, p < 0.001), fibrinogen (5.77 ± 1.48 g/L vs 4.01 ± 1.32 g/L, P < 0.001), white blood cells (8.15 ± 1.90 × 109/L vs 6.85 ± 2.39 × 109/L, p < 0.001) and neutrophils (5.08 ± 1.55 × 109/L vs 4.01 ± 2.04 × 109/L, p = 0.001) are higher in thrombocytosis group, but hemoglobin and albumin are lower compared to non-thrombocytosis group (122.88 ± 17.25 g/L vs 131.51 ± 16.03 g/L, p = 0.002; 37.19 ± 4.73 g/L vs 39.67 ± 3.99 g/L, p = 0.001, respectively). Multivariable logistic regression analysis indicated that higher white blood cells (OR, 1.644; 95% CI, 1.045–2.587; P = 0.032) and fibrinogen (OR, 2.169; 95% CI, 1.237–3.804; P = 0.007) were independently associated with thrombocytosis in SpA patients. The platelet count in the thrombocytosis group treated with anti-TNF-α therapy on week 6 and week 12 were statistically lower than week 0 (225.05 ± 60.58 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001; 201.26 ± 51.48 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001) and conventional therapy (week 6, 225.05 ± 60.58 × 109/L vs 370.00 ± 74.05 × 109/L, p < 0.001; week 12, 201.26 ± 51.48 × 109/L vs 303.13 ± 71.49 × 109/L, p < 0.001).

Conclusion

SpA patients with thrombocytosis have a higher proportion of hip involvement and disease activity compared to non-thrombocytosis SpA patients. The potential risk factors for thrombocytosis in SPA patients were higher white blood cells and fibrinogen. Anti-TNF-α therapy can reduce the increased platelets more effectively and rapidly than conventional treatments in SpA patients with thrombocytosis.

Peer Review reports

Introduction

Spondyloarthritis (SpA) encompasses a heterogeneous group of inflammatory arthritis which share many clinical features and a genetic correlation with human leukocyte antigen B27 (HLA-B27) [1]. Typical clinical manifestation of SpA-related diseases ranges from axial symptom which is inflammatory back pain to peripheral presentations, such as arthritis, enthesitis and dactylitis. Extra-articular manifestations, such as uveitis, inflammatory bowel diseases and psoriasis sometimes can be observed in patients with SpA [2]. According to criteria proposed by the Assessment of Spondyloarthritis International Society (ASAS), patients with SpA can be classified into axial SpA (ax-SpA) and peripheral SpA (p-SpA) based on their different clinical manifestation [3, 4]. The term ax-SpA covers two subgroups: patients with definite radiographic changes of sacroiliac joint (SIJ) defined by modified New York criteria (radiographic axial spondyloarthritis[r-as-SpA], also labeled as ankylosing spondylitis [AS]), and patients without those changes on conventional radiographs (non-radiographic axial spondyloarthritis [nr-as-SpA]) [5]. The latter is regarded as an early stage of r-as-SpA, and inflammation in the SIJ can be detected by magnetic resonance imaging (MRI) before the definite radiographic change develops [6].

Platelets are anucleate fragments generated by megakaryocytes in bone marrow. Despite their well-established role in hemostasis and thrombosis, growing evidence indicates that platelets also play an integral role in innate and adaptive immunity [7, 8]. Previous studies have demonstrated that platelets are associated with the pathogenesis of multiple autoimmune diseases such as rheumatoid arthritis, systemic lupus and multiple sclerosis [7,8,9,10]. In SpA, numerous studies have revealed that platelet counts in patients with SpA are significantly higher than healthy controls, and the elevated platelet count were account for the increased cardiovascular mortality and morbidity in SpA [11,12,13,14,15]. Additionally, platelets were also reported to be related to the new bone formation, severity of inflammation and treatment response in SpA [16, 17], and many platelet-derived immune mediators such as platelet-derived growth factor, transforming growth factor beta were also found to be overexpressed in patients with SpA [18]. However, none of these studies analysis the characteristics of SpA patients with thrombocytosis and investigate risk factors that associated with thrombocytosis in SpA. Herein, we conducted a retrospective study to evaluate the clinical and laboratory and radiological features of SpA patients with thrombocytosis and to explore risk factors that associated with thrombocytosis and to assess the effect of antitumor necrosis factor-α (anti-TNF-α) therapy on platelet count in SpA patients with thrombocytosis.

Methods

Patients

A retrospective study was performed on 145 inpatients with SpA in Fujian Medical university union hospital during the period January 2017 to June 2022. The inclusion criteria were: (1) patients fulfilling the ASAS criteria for axial SpA or the ASAS criteria for peripheral SpA [3, 4]; (2) had a follow-up duration of more than 3 months. The exclusion criteria were as follows: (1) diagnosed with other autoimmune diseases; (2) treatment with anti-platelet drugs; (3) post splenectomy operation; (4) diagnosed with hematological diseases affecting the platelet. This study was approved by the ethics committee of Fujian Medical university union hospital, and informed consent was waived due to the retrospective nature of the study design.

Date collection

Demographic data (gender, age at diagnosis and family history of SpA), initial symptoms (axial, peripheral and extra-articular symptoms), ASAS classification and laboratory parameters (platelet count, hemoglobin, red blood cells, white blood cells, neutrophils, lymphocyte, monocyte, erythrocyte sedimentation rate, C-reactive protein, D-dimer, fibrinogen, albumin and the result of HLA-B27 at first admission) were documented from electronic medical records. Imaging finding, including MRI scan, computer tomography (CT) scan and plane X-rays of the related joints such as SIJ, hip joint and spine were collected. Sacroiliitis on MRI was defined according to the ASAS criteria, as follows: (1) Bone marrow edema (BMO) on a T2-weighted sequence or bone marrow contrast enhancement on a T1-weighted sequence has to be clearly present and located in a typical anatomical area such as subchondral bone. (2) MRI appearance must be highly suggestive of SpA. Definite radiographic sacroiliitis was defined by modified New York criteria (grade 3–4 unilateral or grade 2 bilateral) [19]. Hip joint involvement was defined as hip pain or limited mobility of hip/hips or both acute and chronic inflammatory changes on MRI or radiographic hip joint involvement defined by The Bath Ankylosing Spondylitis Index (BASRI-hip) score > 2 [20]. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [21] score was obtained from electronic medical records to evaluate disease activity, and a cut off value score of 4 was used to discriminate SpA patients of active group from remission group. The normal reference level of platelet count was 100–300 × 109/L according to the laboratory criteria of Fujian Medical university union hospital. Therefore, thrombocytosis is considered a platelet count exceeding 300 × 109/L, and non-thrombocytosis was defined as a blood platelet ≤ 300 × 109/L.

Statistical analysis

Continuous data were presented as mean ± standard deviation and examined by Student’s t-test or paired t-test or one-way ANOVA. Categorical data were expressed as proportion and compared using the Chi-square or Fisher’s exact test. Univariable and multivariable logistic regression analysis was used to identify factors that associated with thrombocytosis in patients with SpA, and variables with P-value < 0.1 in univariable regression analysis was included in multivariable logistic regression analysis. All statistical analysis was performed by SPSS version 26.0 (IBM) and GraphPad Prism 8.0, and a two-side P-value < 0.05 indicated statistically significant.

Results

Comparisons between SpA patients with thrombocytosis and non-thrombocytosis

A total of 145 patients with SpA were included in this study, and thrombocytosis was found in 69 patients (47.59%), and non-thrombocytosis was identified in 76 patients (52.41%). The platelet counts of non-thrombocytosis group were significantly lower than thrombocytosis group (239.51 ± 41.08 × 109/L vs 373.64 ± 63.70 × 109/L, p < 0.001). Compared to SpA patients with non-thrombocytosis, those with thrombocytosis had a higher proportion of hip involvement (60.86% vs 36.84%, p = 0.004) and BASDAI score (4.24 ± 0.55 vs 3.69 ± 0.67, p < 0.001). Erythrocyte sedimentation rate (62.22 ± 41.97 mm/hour vs 27.00 ± 25.93 mm/hour, p < 0.001), C-reactive protein (53.45 ± 47.45 mg/L vs 18.91 ± 31.09 mg/L, p < 0.001), fibrinogen (5.77 ± 1.48 g/L vs 4.01 ± 1.32 g/L, P < 0.001), white blood cells (8.15 ± 1.90 × 109/L vs 6.85 ± 2.39 × 109/L, p < 0.001) and neutrophils (5.08 ± 1.55 × 109/L vs 4.01 ± 2.04 × 109/L, p = 0.001) in thrombocytosis group were higher than non-thrombocytosis group. Albumin (37.19 ± 4.73 g/L vs 39.67 ± 3.99 g/L, p = 0.001) and hemoglobin (122.88 ± 17.25 g/L vs 131.51 ± 16.03 g/L, p = 0.002) were lower in thrombocytosis group compared with non-thrombocytosis group. No statistically significant difference was observed between the two groups in terms of gender, age, family history of SpA, clinical manifestations, ASAS classification, HLA-B27 results, monocytes, lymphocytes, red blood cells, D-dimer, sacroiliitis on MRI and radiographic sacroiliitis (Table 1).

Table 1 Comparison of demographic features and laboratory parameters between spondyloarthritis patients with thrombocytosis and non-thrombocytosis
Full size table

Risk factors of thrombocytosis in patients with SpA

Logistic regression analysis indicated that higher proportion of hip involvement (OR, 2.667; 95% CI, 1.362–5.219; P = 0.004), higher BASDAI score (OR, 3.839; 95% CI, 2.070–7.122; P < 0.001), higher erythrocyte sedimentation rate (OR, 1.031; 95% CI, 1.018–1.044; P < 0.001), higher C-reactive protein (OR, 1.024; 95% CI, 1.013–1.035; P < 0.001), higher fibrinogen (OR, 2.373; 95% CI, 1.747–3.223; P < 0.001), higher white blood cells (OR, 1.334; 95% CI, 1.123–1.585; P < 0.001), higher neutrophils (OR, 1.423; 95% CI, 1.144–1.769; P = 0.002), lower albumin (OR, 0.878; 95% CI, 0.810–0.951; P = 0.001) and hemoglobin (OR, 0.969; 95% CI, 0.950–0.989; P = 0.003) were statistically significant associated with thrombocytosis in patients with SpA. Variables identified in the univariate logistic regression analysis were included in the multivariable logistic regression analysis, and the results revealed that higher fibrinogen (OR, 2.169; 95% CI, 1.237–3.804; P = 0.007) and white blood cells (OR, 1.644; 95% CI, 1.045–2.587; P = 0.032) were independently associated with thrombocytosis in patients with SpA (Table 2).

Table 2 Risk factors for thrombocytosis in patients with spondyloarthritis in univariable and multivariable analysis
Full size table

The effect of antitumor necrosis factor-α therapy on platelet count in SpA patients with thrombocytosis

A total of 31 patients in the thrombocytosis group were treated with conventional therapy (nonsteroidal anti-inflammatory drug and disease-modifying antirheumatic drug only). 38 patients in the thrombocytosis group were treated with anti-TNF-α therapy, and among them 35 patients were treated with etanercept, 2 patients were treated with adalimumab and 1 patient was treated with infliximab. The baseline platelet count (week 0) of anti-TNF-α therapy group and conventional therapy group were 368.26 ± 54.34 × 109/L and 380.23 ± 73.99 × 109/L, respectively (Table 3), and no statistically significant difference was observed between the two groups (p = 0.442). After 6- and 12-weeks treatment, the platelet count of the anti-TNF-α therapy group were statistically lower than conventional therapy group (225.05 ± 60.58 × 109/L vs 370.00 ± 74.05 × 109/L, p < 0.001; 201.26 ± 51.48 × 109/L vs 303.13 ± 71.49 × 109/L, p < 0.001). For the anti-TNF-α therapy group, the platelet count of week 6 and week 12 were statistically lower than week 0 (225.05 ± 60.58 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001; 201.26 ± 51.48 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001), and for conventional therapy group, the platelet count of week 12 were statistically lower than week 0 (303.13 ± 71.49 × 109/L vs 380.23 ± 73.99 × 109/L, p < 0.001), and no statistically significant difference was detected between the week 6 and week 0 (370.00 ± 74.05 × 109/L vs 368.26 ± 54.34 × 109/L, p = 0.078) of the platelet count (Fig. 1).

Table 3 Comparison of platelet count between spondyloarthritis patients with thrombocytosis treated with anti-TNF-α therapy and conventional therapy
Full size table
Fig. 1
figure 1

Platelet count in spondyloarthritis patients with thrombocytosis treated with anti-TNF-α therapy and conventional therapy. * p < 0.05 for 31 spondyloarthritis patients with thrombocytosis treated with conventional therapy between week 12 and week 0. ** p < 0.05 for 38 spondyloarthritis patients with thrombocytosis treated with anti-TNF-α therapy between week 6 and week 0. *** p < 0.05 for 38 spondyloarthritis patients with thrombocytosis treated with anti-TNF-α therapy between week 12 and week 0

Full size image

Discussion

The first part of the study came out that SpA patients with thrombocytosis have a higher proportion of hip involvement, BASDAI score, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, white blood cells and neutrophils, but hemoglobin and albumin are lower compared to non-thrombocytosis group.

SpA is an autoinflammatory disease and inflammation was associated with the pathogenesis of SpA [2]. Erythrocyte sedimentation rate and C-reactive protein are well-established inflammatory indicators that elevated in SpA patients with active disease [11]. Besides, numerous studies reported that a lower albumin and a higher fibrinogen, neutrophils and BASDAI score were observed in SpA patients with more severe disease [13, 22,23,24,25]. These studies validated that fibrinogen, neutrophils and albumin could act as novel biomarkers to reflect disease activity in SpA. Our data show that BASDAI score, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, white blood cells and neutrophils are higher while albumin is lower in SpA patients with thrombocytosis compared to patients with non-thrombocytosis, indicating that SpA patients with thrombocytosis have a high disease activity. Interesting, this study found that a lower hemoglobin was observed in SpA patients with thrombocytosis. Hemoglobin is an important parameter to reflect nutrition status. Anemia is a common complication of inflammatory disease, and some studies reported that 6%-25% of the SpA patients have anemia [26, 27]. In rheumatoid arthritis, anemia is proven to be associated with disease severity [28]. A study found that hemoglobin was lower in AS patients with active disease group than those with stable disease group [27]. Altogether, these data suggest that the disease is more severe in SpA patients with thrombocytosis.

Hip involvement frequently occurs in patients with SpA. Our data show that 60.86% of SpA patients with thrombocytosis have hip involvement, which was slightly higher than previous studies that reported that hip involvement was observed in10-50% of the SpA patients [20]. In SpA patients with non-thrombocytosis group, the proportion of hip involvement was 38.15%, which was lower than thrombocytosis group. One explanation of this is that hip involvement was reported as a classical feature in patients with more severe disease activity [20, 29, 30], and in our study the disease is more severe in thrombocytosis group. Besides, in patients with osteoarthritis, hip osteoarthritis severity was found associate with platelet count. An observational study revealed that a higher platelet count was observed in severe hip osteoarthritis than in mild-moderate hip osteoarthritis (259.18 ± 71.39 × 109/L vs 239.66 ± 33.30 × 109/L, p = 0.03) [31], and a Korean study show that an elevated platelet count is associated with the presence of radiographic hip osteoarthritis in woman [32]. Our study also found that hip involvement was associated with thrombocytosis in SpA in the univariate logistic regression analysis. All these findings suggest that hip involvement have a correlation with platelet counts.

We then explore risk factors associated with thrombocytosis in SpA patients, and our data indicated that higher white blood cells and fibrinogen were associated with thrombocytosis.

Animal model and studies of human tissue demonstrated that white blood cells can bind to activated platelet, and platelet recruitment of white blood cells has been approved to be associated with many inflammatory processes in animal model [33, 34]. Accumulating evidence shows that platelet and white blood cells including neutrophils, lymphocytes and monocytes play crucial roles in the inflammatory process of SpA [12, 35, 36]. Early studies reported that white blood cells and it subtype counts such as neutrophils to lymphocytes ratio, platelet to lymphocytes ratio and monocyte to lymphocytes ratio were higher in patients with SpA compare to health controls, and these parameters could act as novel inflammatory indicators to reflect disease activity in SpA [11, 12, 37]. Consistently, our data indicated that a higher white blood cells was observed in thrombocytosis group which have a more severe disease activity, and both univariate and multivariable logistic regression analysis revealed that white blood cells were independently associated with thrombocytosis in patients with SpA.

Fibrinogen was also considered as an acute phase response protein and was reported that could reflect disease activity in patients with SpA [23, 38]. Recently, two studies show that fibrinogen was statistically higher in SpA patients than healthy controls, and subgroup analysis indicated that platelet counts and fibrinogen were both elevated in SpA patients with a BASDAI score ≥ 4 [13, 23]. Besides, fibrinogen and platelet were key elements of coagulation and fibrinolytic system, and the interactions between fibrinogen and platelet are involved in hemostasis and thrombosis [39]. Previous studies indicated that elevated fibrinogen level and platelet counts are two factors that associated with an increased cardiovascular mortality and morbidity in patients with SpA [14]. Taken together, all these studies underscore a relationship between fibrinogen and platelet in SpA. Consistent with these findings, our study revealed that higher fibrinogen was one of the factors which associated with thrombocytosis in SpA.

The last part of the study demonstrated that anti-TNF-α therapy can reduce the increased platelets more effectively and rapidly than conventional therapy in SpA patients with thrombocytosis.

Anti-TNF-α therapy can be classified in five groups based on different drugs: infliximab, adalimumab, etanercept, golimumab and certolizumab pegol. Many studies and meta-analysis found that platelet count can be reduced by anti-TNF-α therapy in SpA patients and other autoimmune diseases such as rheumatoid arthritis and psoriasis [17, 40, 41]. One study found that the increased platelet counts in AS patients were significantly reduced after 6 months of anti-TNF-α therapy (309 ± 70.00 × 109/L vs 342 ± 69.00 × 109/L) [40]. Consistent with these findings, our data indicated that the platelet count in the thrombocytosis group was statistically lower than baseline platelet count after 6 weeks and 12 weeks anti-TNF-α therapy. Additionally, our study firstly compared the anti-TNF-α therapy with convention therapy in terms of the platelet-lowing effect. In line with early findings [40], our data suggested that convention therapy can also reduce the increase platelet count. But unlike the anti-TNF-α therapy, the platelet count was statistically lower only after 12 weeks of convention treatment, indicating that anti-TNF-α therapy can reduce the increased platelets more effectively and rapidly than conventional treatments. Though the exact mechanism of the platelet-lowing effect of anti-TNF-α therapy remains unclear, TNF-α and its receptor were believed to be associated with this phenomenon. Previous works have confirmed that TNF receptors are expressed by thrombocytes and that TNF-α contributes to platelet-biased hematopoiesis and the hyperreactivity of platelets in bone marrow [17, 42, 43], indicating that anti-TNF-α therapy may have a direct inhibitory effect on platelet production by affecting platelet-biased hematopoiesis. Altogether, our date indicated that anti-TNF-α therapy can effectively reduce increased platelet counts in SpA patients with thrombocytosis.

This study has some limitations. First, it was a single-center study with a relatively small sample size, so the findings of our study need further validation by multicenter study with larger samples. Second, selection bias and recall bias were unavoidable due to the retrospective nature of the study design. Third, some data were incomplete or missing, thus other important parameters used in the evaluation disease activity of SpA such as ASDAS-ESR, ASDAS-CRP were not analysed in the study.

Conclusions

In summary, SpA patients with thrombocytosis have a higher proportion of hip involvement and disease activity compared to non-thrombocytosis group. The potential risk factors for thrombocytosis in SPA patients were higher white blood cells and fibrinogen. Anti-TNF-α therapy can reduce the increased platelets more effectively and rapidly than conventional therapy in SpA patients with thrombocytosis.

Availability of data and materials

The datasets used during the study are available from the corresponding author upon reasonable request.

Abbreviations

SpA:

Spondyloarthritis

anti-TNF-α:

Antitumor necrosis factor-α

HLA-B27:

Human leukocyte antigen B27

ASAS:

The Assessment of Spondyloarthritis International Society

ax-SpA:

Axial spondyloarthritis

p-SpA:

Peripheral spondyloarthritis

SIJ:

Sacroiliac joint

r-as-SpA:

Radiographic axial spondyloarthritis

AS:

Ankylosing spondylitis

nr-as-SpA:

Non-radiographic axial spondyloarthritis

MRI:

Magnetic resonance imaging

CT:

Computer tomography

BASRI-hip:

The Bath Ankylosing Spondylitis Index

BASDAI:

Bath Ankylosing Spondylitis Disease Activity Index

References

  1. Groen SS, Sinkeviciute D, Bay-Jensen AC, Thudium CS, Karsdal MA, Thomsen SF, Schett G, Nielsen SH. Exploring IL-17 in spondyloarthritis for development of novel treatments and biomarkers. Autoimmun Rev. 2021;20(3):102760.

    Article  CAS  PubMed  Google Scholar 

  2. Dougados M, Baeten D. Spondyloarthritis Lancet. 2011;377(9783):2127–37.

    Article  PubMed  Google Scholar 

  3. Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou CT, Dougados M, Huang F, Gu J, Kirazli Y, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2011;70(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  4. Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777–83.

    Article  CAS  PubMed  Google Scholar 

  5. Boonen A, Sieper J, van der Heijde D, Dougados M, Bukowski JF, Valluri S, Vlahos B, Kotak S. The burden of non-radiographic axial spondyloarthritis. Semin Arthritis Rheum. 2015;44(5):556–62.

    Article  PubMed  Google Scholar 

  6. Ortolan A, Kiltz U, Doria A, Aggarwal A, Ramonda R. Do we believe in non-radiographic axial spondyloarthritis? A debate. Autoimmun Rev. 2021;20(1):102703.

    Article  PubMed  Google Scholar 

  7. Koupenova M, Livada AC, Morrell CN. Platelet and Megakaryocyte Roles in Innate and Adaptive Immunity. Circ Res. 2022;130(2):288–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Habets KL, Huizinga TW, Toes RE. Platelets and autoimmunity. Eur J Clin Invest. 2013;43(7):746–57.

    Article  CAS  PubMed  Google Scholar 

  9. Boilard E, Blanco P, Nigrovic PA. Platelets: active players in the pathogenesis of arthritis and SLE. Nat Rev Rheumatol. 2012;8(9):534–42.

    Article  CAS  PubMed  Google Scholar 

  10. Liu X, Gorzelanny C, Schneider SW. Platelets in Skin Autoimmune Diseases. Front Immunol. 2019;10:1453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Al-Osami MH, Awadh NI, Khalid KB, Awadh AI. Neutrophil/lymphocyte and platelet/lymphocyte ratios as potential markers of disease activity in patients with Ankylosing spondylitis: a case-control study. Adv Rheumatol. 2020;60(1):13.

    Article  PubMed  Google Scholar 

  12. Huang Y, Deng W, Zheng S, Feng F, Huang Z, Huang Q, Guo X, Huang Z, Huang X, Pan X, et al. Relationship between monocytes to lymphocytes ratio and axial spondyloarthritis. Int Immunopharmacol. 2018;57:43–6.

    Article  CAS  PubMed  Google Scholar 

  13. Liu M, Huang Y, Huang Z, Zhong Z, Deng W, Huang Z, Huang Q, Li T. The role of fibrinogen to albumin ratio in ankylosing spondylitis: Correlation with disease activity. Clin Chim Acta. 2020;505:136–40.

    Article  CAS  PubMed  Google Scholar 

  14. Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT. Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum. 2004;34(3):585–92.

    Article  PubMed  Google Scholar 

  15. Zhou Z, Chen H, Ju H, Sun M, Jin H. Platelet indices in patients with chronic inflammatory arthritis: a systematic review and meta-analysis. Platelets. 2020;31(7):834–44.

    Article  CAS  PubMed  Google Scholar 

  16. Czepiel M, Stec M, Korkosz M, Gula Z, Blyszczuk P, Baran J, Siedlar M. Down-Regulation of Dkk-1 in Platelets of Patients With Axial Spondyloarthritis. Arthritis Rheumatol. 2021;73(10):1831–4.

    Article  CAS  PubMed  Google Scholar 

  17. Qian H, Chen R, Wang B, Yuan X, Chen S, Liu Y, Shi G. Associations of Platelet Count with Inflammation and Response to Anti-TNF-alpha Therapy in Patients with Ankylosing Spondylitis. Front Pharmacol. 2020;11:559593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang T, Meng S, Chen P, Wei L, Liu C, Tang D, Liu D, Jiang Z, Hong X. Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets. Exp Cell Res. 2021;409(1):112895.

    Article  CAS  PubMed  Google Scholar 

  19. Lambert RG, Bakker PA, van der Heijde D, Weber U, Rudwaleit M, Hermann KG, Sieper J, Baraliakos X, Bennett A, Braun J, et al. Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Ann Rheum Dis. 2016;75(11):1958–63.

    Article  PubMed  Google Scholar 

  20. Zhang K, Zheng Y, Han Q, Liu Y, Wang W, Ding J, Wang Y, Zhang B, Jia J, Zheng M, et al. The Clinical and MRI Effect of TNF-alpha Inhibitors in Spondyloarthritis Patients With Hip Involvement: A Real-World Observational Clinical Study. Front Immunol. 2021;12:740980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21(12):2286–91.

    CAS  PubMed  Google Scholar 

  22. Pamukcu M, Duran TI. Could C-Reactive Protein/Albumin Ratio be an Indicator of Activation in Axial Spondyloarthritis? J Coll Physicians Surg Pak. 2021;30(5):537–41.

    PubMed  Google Scholar 

  23. Ding Y, Xue L. The potential value of fibrinogen to albumin ratio (FAR) in the assessment of inflammation in spondyloarthritis. BMC Musculoskelet Disord. 2022;23(1):864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tang Y, Yang P, Wang F, Xu H, Zong SY. Association of polymorphisms in ERAP1 and risk of ankylosing spondylitis in a Chinese population. Gene. 2018;646:8–11.

    Article  CAS  PubMed  Google Scholar 

  25. Zhong Z, Huang Y, Liu Y, Chen J, Liu M, Huang Q, Zheng S, Guo X, Deng W, Li T. Correlation between C-Reactive Protein to Albumin Ratio and Disease Activity in Patients with Axial Spondyloarthritis. Dis Markers. 2021;2021:6642486.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Weiss G, Schett G. Anaemia in inflammatory rheumatic diseases. Nat Rev Rheumatol. 2013;9(4):205–15.

    Article  CAS  PubMed  Google Scholar 

  27. Hu Y, Jiang WZ, Pan CL, Wang T. Active ankylosing spondylitis increases blood loss during total hip arthroplasty for a stiff hip joint. BMC Musculoskelet Disord. 2020;21(1):243.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wolfe F, Michaud K. Anemia and renal function in patients with rheumatoid arthritis. J Rheumatol. 2006;33(8):1516–22.

    PubMed  Google Scholar 

  29. Huang ZG, Zhang XZ, Hong W, Wang GC, Zhou HQ, Lu X, Wang W. The application of MR imaging in the detection of hip involvement in patients with ankylosing spondylitis. Eur J Radiol. 2013;82(9):1487–93.

    Article  PubMed  Google Scholar 

  30. Vander Cruyssen B, Vastesaeger N, Collantes-Estevez E. Hip disease in ankylosing spondylitis. Curr Opin Rheumatol. 2013;25(4):448–54.

    Article  CAS  PubMed  Google Scholar 

  31. Tasoglu O, Sahin A, Karatas G, Koyuncu E, Tasoglu I, Tecimel O, Ozgirgin N. Blood mean platelet volume and platelet lymphocyte ratio as new predictors of hip osteoarthritis severity. Medicine (Baltimore). 2017;96(6):e6073.

    Article  PubMed  Google Scholar 

  32. Kwon YJ, Koh IH, Chung K, Lee YJ, Kim HS. Association between platelet count and osteoarthritis in women older than 50 years. Ther Adv Musculoskelet Dis. 2020;12:1759720X20912861.

  33. Schrottmaier WC, Mussbacher M, Salzmann M, Assinger A. Platelet-leukocyte interplay during vascular disease. Atherosclerosis. 2020;307:109–20.

    Article  CAS  PubMed  Google Scholar 

  34. Chimen M, Evryviadou A, Box CL, Harrison MJ, Hazeldine J, Dib LH, Kuravi SJ, Payne H, Price JMJ, Kavanagh D, et al. Appropriation of GPIbalpha from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation. Haematologica. 2020;105(5):1248–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Martinez-Ramos S, Rafael-Vidal C, Pego-Reigosa JM, Garcia S. Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies. Cells. 2022;11(3).

  36. Stavre Z, Bridgewood C, Zhou Q, Maeda Y, Huang TT, Karman J, Khan A, Giryes S, Sharif K, McGonagle D, et al. A role for neutrophils in early enthesitis in spondyloarthritis. Arthritis Res Ther. 2022;24(1):24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liang T, Chen J, Xu G, Zhang Z, Xue J, Zeng H, Jiang J, Chen T, Qin Z, Li H, et al. Platelet-to-Lymphocyte Ratio as an Independent Factor Was Associated With the Severity of Ankylosing Spondylitis. Front Immunol. 2021;12:760214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood. 2019;133(6):511–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hou Y, Carrim N, Wang Y, Gallant RC, Marshall A, Ni H. Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. J Biomed Res. 2015;29.

  40. Yazici S, Yazici M, Erer B, Erer B, Calik Y, Bulur S, Ozhan H, Ataoglu S. The platelet functions in patients with ankylosing spondylitis: anti-TNF-alpha therapy decreases the mean platelet volume and platelet mass. Platelets. 2010;21(2):126–31.

    Article  CAS  PubMed  Google Scholar 

  41. Yazici S, Yazici M, Erer B, Erer B, Calik Y, Ozhan H, Ataoglu S. The platelet indices in patients with rheumatoid arthritis: mean platelet volume reflects disease activity. Platelets. 2010;21(2):122–5.

    Article  CAS  PubMed  Google Scholar 

  42. Davizon-Castillo P, McMahon B, Aguila S, Bark D, Ashworth K, Allawzi A, Campbell RA, Montenont E, Nemkov T, D’Alessandro A, et al. TNF-alpha-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging. Blood. 2019;134(9):727–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dib PRB, Quirino-Teixeira AC, Merij LB, Pinheiro MBM, Rozini SV, Andrade FB, Hottz ED. Innate immune receptors in platelets and platelet-leukocyte interactions. J Leukoc Biol. 2020;108(4):1157–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

Not applicable.

Author information

Author notes

  1. Linan Deng and Pingping Zheng contributed equally to this work

Authors and Affiliations

  1. Department of Rheumatology, Fuzhou Second Hospital, 47 Shangteng Road, Cangshan District, Fuzhou, 350007, China

    Linan Deng

  2. Department of Burns and Wounds, Fujian Medical University Union Hospital, Fuzhou, China

    Pingping Zheng

Authors
  1. Linan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pingping Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LD contributed to the writing and editing of the manuscript. PZ contributed to data collection. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Linan Deng.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of Fujian Medical university union hospital. All methods were performed in accordance with the Declaration of Helsinki and the relevant guidelines and regulations. Informed consent to participate was waived by the ethics committee of Fujian Medical university union hospital due to the retrospective nature of the study design.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, L., Zheng, P. Thrombocytosis in patients with spondyloarthritis: a case–control study. BMC Musculoskelet Disord 24, 195 (2023). https://doi.org/10.1186/s12891-023-06304-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12891-023-06304-1

Keywords

BMC Musculoskeletal Disorders

ISSN: 1471-2474

Contact us