血栓弹力与炎症性肠病患者

抽象

Purpose。Patients with inflammatory bowel disease (IBD) frequently suffer from venous thromboembolic events, and the risk of thromboembolism increases along with disease activity. This study was conducted to discover novel thrombophilic markers using thromboelastography (TEG) and to evaluate the relation between the predisposing factors and the activity of disease in Chinese patients with Crohn’s disease (CD) and ulcerative colitis (UC).Methods。Thirty-four patients with CD, 29 patients with UC, and 53 healthy volunteers were enrolled into this study. Blood levels of ， ， 角度， ，maximal amplitude (MA), and LY30 with TEG were determined.Results。的平均值 ， ， 角度， ，一个nd MA were significantly different in patients with CD and UC compared with the healthy individuals. Patients with active CD had different ， 角度， ，一个nd MA levels compared with patients in remission ( ， ， ，一个nd ）。Levels of ， 角度， ，一个nd MA were also significantly different in active UC patients compared with those in remission ( ， ， ，一个nd ）。除了level in the CD group, differences in all TEG levels between healthy individuals and IBD patients in remission were not statistically significant. No statistical differences were observed in LY30 among patients with active phase, patients in remission, and the healthy individuals.Conclusion。在中国pati Thrombophilic缺陷是很常见的ents with IBD, and TEG can be considered a new direction to anticoagulant thromboprophylaxis in IBD.

1。Introduction

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory systemic disease which primarily affects the bowels and causes extraintestinal manifestations simultaneously [1，2]。The patients with IBD have an approximately 3-fold higher risk of venous thromboembolism (VTE) compared with persons without IBD, and the risk of VTE increases along with disease activity [3，4]。Anticoagulant thromboprophylaxis is recommended in active IBD given that there is no severe active bleeding [五]。Several studies using various markers of the coagulation system have revealed the risk of thrombosis in IBD patients, such as protein C, protein S, and antithrombin III [6，7]。However, the heterogeneity in the identified studies remains and the precise mechanism of hypercoagulability in IBD is not understood well.

Thromboelastography (TEG) measures the integrated dynamics of the coagulation process from clot formation to clot consistency, which provides global information about the balance between both sides of coagulation, clot strength, and lysis [8]。因此，TEG很可能是用于评价凝血状态和抗凝剂治疗的反应是有价值的。目前，TEG已经在不同的临床条件下，如在怀孕的患者使用的，在产科患者，肝移植，心脏手术，心肌梗死，并在外伤患者[9-14]。一个TEG的最关键的优势是全面的全球评估前的例行试验[凝血过程15]。However, TEG was not reported in IBD with an abnormal coagulation status till now.

本研究旨在确定TEG was valuable in assessing hypercoagulable states of IBD. Our findings will provide novel references to anticoagulant thromboprophylaxis in IBD.

2.方法

2。1。Patients and Healthy Volunteers

这项研究是与当地研究伦理委员会批准实施。从入学前每位受试者得到本研究的书面同意。六十三IBD患者随访南京大学医学院附属鼓楼医院消化科的研究对象。In the CD group, there were 22 men and 12 women, with age ranging from 16 to 53 yr. The UC group included 13 men and 16 women, with age ranging from 19 to 54 yr. Fifty-three healthy volunteers were enrolled as the control group. There were no statistical differences for gender and age among the three groups. The diagnosis of CD and UC was on the basis of standard criteria [16]。Crohn’s Disease Activity Index (CDAI) score was used to evaluate disease activity in CD [17]，和在UC [使用梅奥得分系统的变形例18，19]。A CDAI score equal or higher than 150 in patients with CD and a Mayo score equal or higher than 3 in patients with UC were considered to manifest clinical active disease. None of the IBD patients and healthy volunteers had a history of previous thromboembolism. The clinical data of IBD patients and controls are summarized in Table1。

2.2。实验室研究

全血，通过专家与护士在窝cubitalis干净的静脉穿刺收集。The first 5 ml of each sample was discarded. 5-8 ml of whole blood was then collected into a 10 ml citrated tube. The samples were kept at 15-25°C and analyzed within 2 hours from sampling. Standard TEG was performed with the TEG 5000 Thrombelastograph Hemostasis Analyzer System (Haemonetics Corporation, Niles, USA) according to the manufacturer’s protocol. The following values were evaluated with a TEG test:（分钟），（分钟），Angle (degrees),（达因/厘米2）maximal amplitude (MA, mm), and LY30 (percentage).is the time until the TEG tracing amplitude returns to 2 mm, andis derived fromuntil the amplitude reaches 20 mm which reflects the speed of clot strengthening.Angle is generated by the slope of TEG tracing from the horizontal line of也代表凝块加强。MA测量凝块的最大力量，reflects the clot strength or firmness. LY30, recorded as percent lysis, measures the clot lysis as the decay with MA over 30 minutes.

The TEG instrument was validated for quality assurance through daily quality control procedures with normal and abnormal controls for operational checks and calibration verification. The quality control methods are based on the recommendations of the Clinical and Laboratory Standards Institute, the US Clinical Laboratory Improvement Amendments, and the performance standards of TEG analyzer.

2。3。Statistical Analysis

The data were expressed as 一个nd were analyzed with SPSS software, version 19.0 (SPSS Inc., Chicago, IL, USA). Statistical differences were evaluated by one-way ANOVA, using LSD, SNK and Dunnett’s methods. Results were considered statistically significant differences when the analysis reached avalue of < 0.05.

3。Results

CD的分布显示55.9％回结肠，26.5％的结肠和17.6％回肠参与。UC幅度58.6％全结肠炎，左双面34.5％，和6.9％直肠炎。共有7周脓肿，肠3个狭窄，6口肛瘘，1对例消化道CD患者出血。只有一个并发症中毒性巨结肠的出现在UC患者。二十一（61.8％）例CD和19（65.5％）患者表现出UC活动性疾病（表1）。

一个nd各级CD患者进行统计学降低与健康人相比（ ， ）。 角度， ，一个nd MA were significantly higher in patients with CD compared with healthy individuals ( ， ，一个nd ）。的平均值一个ndwere statistically lower in patients with UC than in the healthy control group ( ， ）。的平均值角度， ，一个nd MA were significantly higher in patients with UC than in the healthy control group ( ， ，一个nd ）。There was no difference between IBD patients and healthy individuals in LY30 (Table2）。

此外，在患有活动相位TEG的水平与所述患者中缓解了比较。的平均值在患有活动相位进行统计学降低与缓解期患者相比（ ）。Levels of角度， ，一个nd MA were significantly higher in patients with active phase than patients in remission ( ， ，一个nd ）。有统计差异一个ndbetween IBD patients in remission and healthy individuals ( ， ）(Table3）。

Patients with CD and UC were also evaluated separately. Patients with active CD had lower和更高角度， ，一个nd MA levels than patients in remission ( ， ， ，一个nd ）。患有活动性UC有较低和更高角度， ，一个nd MA levels than patients in remission ( ， ， ，一个nd ）。除了level in the CD group ( ）differences in all TEG levels between healthy individuals and patients in remission in both CD and UC groups were not statistically significant. No statistical differences were observed in LY30 among patients with active phase, patients in remission, and the healthy individuals (Table3）。

4。Discussion

最近，对患者的血液高凝状态与IBD的意见作出了重大变化。这项研究是第一个评价IBD患者TEG的价值。我们的主要发现是，IBD患者与对照组相比不同的TEG参数的更多高凝。这是通过统计学差异证明 ， ， 角度， ，和MA，但LY30没有差异。另外一个重要发现是，活跃IBD患者相比，缓解期患者均对一些参数TEG高凝。我们不能推断，如果反映在TEG异常早IBD患者的血液高凝状态或为由此造成的后果。然而，我们确实发现了很大的变异IBD患者中的凝血过程中所反映的TEG值。反映凝血因子活性，这是在所有受影响最大的参数分析了具体的凝血因子缺乏TEG变量[20]。一个ndAngle are supposed to represent the propagation phase of the enzymatic factors related to clot strengthening, which is mostly accomplished by fibrin polymerization and fibrinogen cleavage in the phase of clotting [21]。值显示成熟凝块的强度。大多数的总归因于血小板和纤维蛋白[之间的相互作用22]。MA represents the greatest strength accomplished by the clot, which assesses the combination of platelet quantity and function as well as the activity of fibrinogen rather than a simple effect [23]。LY30 is calculated 30 minutes after achieving MA with the percent reduction of clot strength as a standard measurement of fibrinolysis [24]。所有的侦探TEG指标中，只有LY30具有从CD和UC例，对照组，这意味着IBD患者的纤溶功能不受损害和高凝状态的机制，可在IBD被建议没有显著差异。有趣的是，一些TEG指标为活性和IBD缓解期差异具有统计学意义，但有些人不是在这项研究中。这种差异可能与CD和UC分期的主观性。

At present, the data were sufficient to determine TEG as a method that might be valuable in assisting us to understand the target of anticoagulant thromboprophylaxis therapy better. However, the study still had several limitations. First, this study could be defective because of the various operators which carried out TEG detection. To minimize the deviation of TEG based on the existing imprecision, daily quality control was carried out carefully. In addition, studies in large population are needed to reduce imprecision with TEG detection as far as possible. Second, during the treatment of IBD, drugs such as glucocorticoids and immunosuppressants may affect the TEG results and become a confounding variable. Finally, we only measured the values of TEG, while the molecular mechanisms of coagulation and fibrinolysis were not be explored in depth. However, we think relevant molecular markers will gradually be explored with the subsequent studies.

5。结论

This study demonstrates that hypercoagulability exists in many IBD patients and is related to disease activity. Further study on the basis of present data will determine if TEG measuring is valuable for the dynamic aspects of coagulation and anticoagulant thromboprophylaxis therapy.

数据可用性

用于支持研究的结果的数据可从上请求相应的作者。

Conflicts of Interest

The authors declare that there are no conflicts of interest.

作者的贡献

研究设计是由XQ张进行。数据收集由YH沉，LL石，和JJ张进行。统计分析是由ZQ刘进行。数据解释是由H朱和YL姚明进行。手稿准备工作由YH沉和张JJ进行。文献检索由YH沉，LL石，和XP邹进行。永华沉亮亮石，和张娟娟同样促成了这一工作。

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