Open Access Research BMJ Open: first published as 10.1136/bmjopen-2017-016719 on 4 November 2017. Downloaded from Association between coagulation function and patients with primary angle closure glaucoma: a 5-year retrospective case–control study Shengjie Li,1 Yanting Gao,1 Mingxi Shao,1 Binghua Tang,1 Wenjun Cao,1,2 Xinghuai Sun2,3,4,5 To cite: Li S, Gao Y, Shao M, ABSTRACT Strengths and limitations of this study et al. Association between Objective To evaluate the association between coagulation function and coagulation function and patients with primary angle patients with primary ► This is the first study focusing on the evaluation of closure glaucoma (PACG). angle closure glaucoma: a the coagulation function in primary angle closure 5-year retrospective case– Design A retrospective, hospital-based, case–control glaucoma (PACG) and its relationship with disease control study. BMJ Open study. severity. 2017;7:e016719. doi:10.1136/ Setting Shanghai, China. ► The large number of studied subjects. bmjopen-2017-016719 Participants A total of 1778 subjects were recruited from ► The detailed demographic and clinical data of the Eye & ENT Hospital of Fudan University from January ► Prepublication history and studied subjects. additional material for this paper 2010 to December 2015, including patients with PACG ► The nature of this study was a single eye centre, are available online. To view (male=296; female=569) and control subjects (male=290; retrospective case–control study. please visit the journal (http:// female=623). ► Statistical power analysis for specificity ability was dx. doi. org/ 10. 1136/ bmjopen- Outcome measures Sociodemographic data and limited. 2017- 016719). clinical data were collected. The one-way analysis ► Less than 2% of patients with PACG revealed of variance test was used to compare the levels of abnormal values for activated partial thromboplastin Received 4 March 2017 Revised 2 August 2017 laboratory parameters among the mild, moderate and time, prothrombin time, thrombin time and mean Accepted 2 August 2017 severe PACG groups. Multivariate logistic regression platelet volume that strictly limit the clinical use of analyses were performed to identify the independent risk such findings. factors for PACG. The nomogram was constructed based http://bmjopen.bmj.com/ on the logistic regression model using the R project for statistical computing (R V.3.3.2). Results The activated partial thromboplastin time INTRODUCTION (APTT) of the PACG group was approximately 4% Glaucoma, the second leading cause of blind- shorter (p<0.001) than that of the control group. The ness worldwide, is a group of heterogeneous prothrombin time (PT) was approximately 2.40% optic neuropathies characterised by progres- shorter (p<0.001) in patients with PACG compared sive retinal ganglion cell death and visual with the control group. The thrombin time was also field loss.1 Based on a population-based study, on October 1, 2021 by guest. Protected copyright. approximately 2.14% shorter (p<0.001) in patients with there will be 59.51 million people with glau- PACG compared with the control group. The level of coma by 2020 in Asia alone, with that number D-dimer was significantly higher (p=0.042) in patients with PACG. Moreover, the mean platelet volume (MPV) expected to increase to 80.87 million patients of the PACG group was significantly higher (p=0.013) by 2040. As primary angle closure glaucoma than that of the control group. A similar trend was (PACG) appears to cause blindness more observed when coagulation parameters were compared frequently than primary open angle glau- between the PACG and control groups with respect to coma (POAG),2 3 it has become an important gender and/or age. Multiple logistic regression analyses public visual health issue.4 Although elevated revealed that APTT (OR=1.032, 95% CI 1.000 to 1.026), intraocular pressure is regarded as a major PT (OR=1.249, 95% CI 1.071 to 1.457) and MPV risk factor for glaucoma, the exact patho- For numbered affiliations see (OR=1.185, 95% CI 1.081 to 1.299) were independently genic mechanism of glaucoma is still not end of article. associated with PACG. Conclusion Patients with PACG had a shorter clearly understood. A number of studies Correspondence to coagulation time. Our results suggest that coagulation have investigated the various risk factors that Dr Wenjun Cao; might cause glaucomatous damage, one of wgkjyk@ aliyun. com and function is significantly associated with patients with Dr Xinghuai Sun; PACG and may play an important role in the onset and which includes the hypercoagulable state of 5–7 xhsun@ shmu. edu. cn development of PACG. ocular blood flow. Li S, et al. BMJ Open 2017;7:e016719. doi:10.1136/bmjopen-2017-016719 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2017-016719 on 4 November 2017. Downloaded from Some have found a hypercoagulable state and elevated which influenced their coagulation function. Control blood viscosity in patients with POAG or normal tension subjects had no ocular diseases, blood system diseases, glaucoma (NTG).8–11For example, O'Brien et al11 active infection or major systemic diseases (acute inflam- reported that patients with glaucoma had elevated levels mation, hyperuricaemia, cardiac, autoimmune disease of prothrombin fragments 1+2 and D-dimer compared and cancer) that could possibly affect their coagulation with both NTG and controls, which could contribute to function. Moreover, those on treatment with agents impaired blood circulation to the optic nerve and thus affecting laboratory parameters, including patients with lead to glaucomatous damage. A hypercoagulable state haematological disorders and chemotherapy treatment, and elevated blood viscosity can also reduce blood flow were also excluded. Control subjects were also excluded in eyes leading to ischaemia and dysregulation of oxygen if there was any family history of glaucoma. delivery, which might be associated with the progression Given the potentially higher risk of PACG blindness of visual field loss in glaucoma.12–15 Li et al16 performed in women,19–21 the PACG subjects were categorised into a meta-analysis and showed significantly elevated endo- female and male subgroups to shed light on the role of thelin-1 plasma concentrations in glaucoma which the coagulation function in PACG development between suggested that vascular dysfunction may be involved genders. Several studies have reported that the preva- in the pathogenesis of glaucoma. Vascular dysfunction lence of PACG increases with advancing age, especially further exacerbates the hypercoagulable state and reduc- in China.22 23 Therefore, a subgroup analysis by gender tion of blood flow in eyes with glaucoma. Moreover, our across different age groups (subgroups: 0–59 years and previous study reported that the mean platelet distribu- 60+ years) was performed to shed light on the possible tion width (PDW) and mean platelet volume (MPV) were role of the coagulation function in PACG development increased in patients with neovascular glaucoma.17 There with increasing age. In male and female subgroups, the are, however, only a few published studies focusing on the patients with PACG were divided into three groups with relationship between coagulation function and patients different disease severities based on visual fields mean with PACG. deviation (MD), that is, mild (MD≤6.00 dB), moderate Therefore, this study was designed to analyse the (12 dB≥MD>6 dB) and severe (MD>12 dB).18 24 25 indices of coagulation function in patients with PACG, Laboratory parameters and subsequently explore whether the alteration of the Platelet parameters including MPV, PDW, PCT (platelet- blood stream state may be involved in the pathophysio- crit) and PLT (platelet count) were measured with the logical mechanism of PACG. Mindray BC-5500 (Shenzhen, China) automatic blood counting system. The blood samples for platelet param- eters were collected in ethylenediaminetetraacetic acid MATERIALS AND METHODS tubes. Coagulation parameters including activated partial Subjects thromboplastin time (APTT), prothrombin time (PT), http://bmjopen.bmj.com/ This was a retrospective case–control study. Patients with thrombin time (TT) and D-dimer were measured with PACG were recruited from the department of ophthal- STAGO STA-R Evolution. The blood samples for coagu- mology inpatient service at the Eye & ENT Hospital of lation parameters were collected in sodium citrate antico- Fudan University between January 2010 and December agulation tubes. 2015. Up to 913 age-matched and sex-matched normal controls were consecutively recruited from subjects Data analysis who participated in yearly health screenings during The data were analysed using SPSS V.13.0 (SPSS). Normality the study period. The study was approved by the of the data was assessed with the Kolmogorov-Smirnoff test. 2 on October 1, 2021 by guest. Protected copyright. Ethics Committee of the Eye & ENT Hospital of Fudan The independent student’s t-test and χ test were used for University (EENT2015011), Shanghai, China, and was comparison of patient characteristics between the PACG conducted according to the Declaration of Helsinki. and control groups. The one-way analysis of variance test Written informed consent for the use of any clinical data was used to compare the levels of laboratory parameters in research was obtained for all patients at the time of among the mild, moderate and severe PACG groups. admission to the Eye & ENT Hospital of Fudan University. Multivariate logistic regression analyses were performed to The study cohort flow diagram is shown in online supple- identify the independent risk factors for PACG. ORs with mentary figure 1. This database has been used previously 95% CIs were estimated using multivariate logistic regres- to study patients with glaucoma.18 sion analyses. The nomogram was constructed based on the logistic regression model using the R project for statis- Inclusion criteria tical computing (R V.3.3.2). A p value of less than 0.05 was Our previous study has described the inclusion criteria considered statistically significant.