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  • Title: Changes in coagulation indices and D-dimer levels in hypertriglyceridemic acute pancreatitis and their value in predicting disease severity.
    Author: Gou Y, Yao L, Cao J.
    Journal: Zhong Nan Da Xue Xue Bao Yi Xue Ban; 2023 Jul 28; 48(7):1050-1058. PubMed ID: 37724408.
    Abstract:
    OBJECTIVES: Hypertriglyceridemic acute pancreatitis (HTG-AP) is one of the common acute and severe cases of digestive system. Incidence of HTG-AP is increasing year by year, and there is a trend of younger and severe cases. Early identification of severe patients and timely intervention are conducive to improve the prognosis. Dysfunction of coagulation and fibrinolysis systems plays an important role in the development of HTG-AP. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are sensitive indicators of exogenous and endogenous coagulation system, respectively. Fibrinogen (FIB) is an acute reactive protein with coagulation function. D-dimer is a sensitive index to judge the abnormality of coagulation and fibrinolysis system. This study aims to investigate the changes of coagulation parameters and D-dimer level in patients with HTG-AP and their value in predicting the severity of the disease. METHODS: The clinical data of 189 HTG-AP patients admitted to Jiangjin Hospital Affiliated to Chongqing University (Jiangjin District Central Hospital of Chongqing) from January 2019 to December 2020 were collected, including gender, age, medical history, complications, causes, and acute physiology and chronic health evaluation II (APACHE II) scores. According to the severity of the disease, the patients were divided into a mild HTG-AP group and a severe HTG-AP group. The changes of coagulation indexes (PT, APTT and FIB), D-dimer and C-reactive protein (CRP) levels were detected. Coagulation indexes, D-dimer level and disease severity (CRP level, APACHE II scores) were compared between the 2 groups. Spearman correlation analysis was used to analyze the correlation between the above indexes. Univariate and multivariate binary logistic regression analysis were used to identify the independent risk factors for severe HTG-AP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of PT, FIB, and D-dimer for the severity of HTG-AP. RESULTS: There were significant differences in gender between the mild HTG-AP group and the severe HTG-AP group (P<0.05). There was no significant difference in age, recurrence rate and incidence of complications between the 2 groups (all P>0.05). The basic conditions of the 2 groups were similar and comparable. PT, FIB and D-dimer levels in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.001). There was no significant difference in APTT between the 2 groups (P>0.05). The CRP level and APACHE II scores in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.05). Spearman correlation analysis showed that PT, FIB and D-dimer were positively correlated with CRP and APACHE II scores (all P<0.05), while APTT was not correlated with CRP and APACHE II scores (all P>0.05). Logistic regression analysis showed that prolonged PT and elevated D-dimer level were independent risk factors for severe HTG-AP (both P<0.05). ROC curve analysis showed that the AUC of PT for predicting severe HTG-AP was 0.764 (95% CI 0.690 to 0.837, P<0.001), when PT>14.40 s, the sensitivity, specificity, positive predictive value, and negative predictive value were 63.07%, 79.03%, 59.42%, and 80.00%, respectively. TheAUC of FIB for predicting severe HTG-AP was 0.669 (95% CI 0.588 to 0.751, P<0.001), when FIB>4.18 g/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 61.53%, 70.17%, 49.38%, and 76.85%, respectively. The AUC of D-dimer for predicting severe HTG-AP was 0.753 (95% CI 0.680 to 0.826, P<0.001), when D-dimer>1.28 μg/mL, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.84%, 66.12%, 53.33%, and 82.82%, respectively. The AUC of PT combined with D-dimer for predicting severe HTG-AP was 0.797. CONCLUSIONS: There are abnormalities in coagulation and fibrinolytic system in patients with HTG-AP in the early stage. PT, FIB and D-dimer levels are increased with the aggravation of the AP, and have a positively correlation with it. Elevated PT and D-dimer level are independent risk factors for severe HTG-AP. PT combined with D-dimer may be a sensitive indicator for prediction of the severity of HTG-AP in early phase. 目的: 高甘油三酯血症性急性胰腺炎(hypertriglyceridemic acute pancreatitis,HTG-AP)是消化系统常见的急重症之一,其发病率逐年攀升,且有年轻化、重症化趋势,早期识别重症患者并及时干预有利于改善预后。凝血和纤溶系统功能紊乱在HTG-AP病程发展中扮演重要角色。凝血功能相关指标凝血酶原时间(prothrombin time,PT)与活化部分凝血活酶时间(activated partial thromboplastin time,APTT)分别属于外源性和内源性凝血系统的敏感性判断指标。纤维蛋白原(fibrinogen,FIB)是具有凝血功能的急性反应性蛋白质。D-二聚体是凝血和纤溶系统异常的敏感性判断指标。本研究旨在探讨HTG-AP患者凝血指标和D-二聚体水平变化及其预测疾病严重程度的价值。方法: 收集2019年1月至2020年12月重庆大学附属江津医院(重庆市江津区中心医院)收治的189例HTG-AP患者的临床资料,包括性别、年龄、病史、合并症、病因及急性生理学和慢性健康状况评价II(acute physiology and chronic health evaluation II,APACHE II)评分。根据疾病严重程度将患者分为轻度HTG-AP组和重度HTG-AP组。检测2组凝血指标(PT、APTT和FIB)、D-二聚体和C反应蛋白(C-reactive protein,CRP)水平变化。对2组患者凝血指标、D-二聚体水平及病情严重程度(CRP水平、APACHE II评分)进行比较。采用Spearman相关性分析对上述指标进行相关性分析;单因素和多因素二元logistic回归分析寻找HTG-AP重症化的独立危险因素;受试者操作特征(receiver operating characteristic,ROC)曲线及曲线下面积(area under the curve,AUC)分析PT、FIB、D-二聚体对HTG-AP病情严重程度的预测价值。结果: 轻度HTG-AP组和重度HTG-AP组患者性别差异具有统计学意义(P<0.05),2组患者年龄、复发占比及合并症发生率差异均无统计学意义(均P>0.05),患者的基本情况相似,具有可比性。重度HTG-AP组患者PT、FIB和D-二聚体较轻度HTG-AP组患者均明显增加(均P<0.001),2组患者APTT的差异无统计学意义(P>0.05)。重度HTG-AP组患者CRP水平、APACHE II评分均显著高于轻度HTG-AP组患者(均P<0.05)。Spearman相关性分析结果显示:患者凝血指标PT、FIB和纤溶系统指标D-二聚体分别与CRP、APACHE II评分呈正相关(均P<0.05),患者APTT与CRP、APACHE II评分均无相关性(均P>0.05)。Logistic回归分析结果提示患者PT延长、D-二聚体水平升高均是HTG-AP重症化的独立危险因素(均P<0.05)。ROC曲线分析结果显示:PT预测HTG-AP重症化的AUC为0.764(95% CI 0.690~0.837,P<0.001),当PT>14.40 s时,其灵敏度、特异度、阳性预测值和阴性预测值分别为63.07%、79.03%、59.42%和80.00%。FIB预测HTG-AP重症化的AUC为0.669(95% CI 0.588~0.751,P<0.001),当FIB>4.18 g/L时,其灵敏度、特异度、阳性预测值和阴性预测值分别为61.53%、70.17%、49.38%和76.85%。D-二聚体预测HTG-AP重症化的AUC为0.753(95% CI 0.680~0.826,P<0.001),当D-二聚体>1.28 μg/mL时,其灵敏度、特异度、阳性预测值和阴性预测值分别为73.84%、66.12%、53.33%和82.82%。PT联合D-二聚体预测HTG-AP重症化的AUC为0.797。结论: HTG-AP患者早期凝血和纤溶系统存在异常,PT、FIB、D-二聚体水平随着病情加重而升高,并且与疾病严重程度呈正相关,PT延长、D-二聚体水平升高是HTG-AP重症化的独立危险因素,PT和D-二聚体水平可能是早期预测HTG-AP疾病严重程度的实验室指标。. OBJECTIVE: Hypertriglyceridemic acute pancreatitis (HTG-AP) is one of the common acute and severe cases of digestive system. Incidence of HTG-AP is increasing year by year, and there is a trend of younger and severe cases. Early identification of severe patients and timely intervention are conducive to improve the prognosis. Dysfunction of coagulation and fibrinolysis systems plays an important role in the development of HTG-AP. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are sensitive indicators of exogenous and endogenous coagulation system, respectively. Fibrinogen (FIB) is an acute reactive protein with coagulation function. D-dimer is a sensitive index to judge the abnormality of coagulation and fibrinolysis system. This study aims to investigate the changes of coagulation parameters and D-dimer level in patients with HTG-AP and their value in predicting the severity of the disease. METHODS: The clinical data of 189 HTG-AP patients admitted to Jiangjin Hospital Affiliated to Chongqing University (Jiangjin District Central Hospital of Chongqing) from January 2019 to December 2020 were collected, including gender, age, medical history, complications, causes, and acute physiology and chronic health evaluation II (APACHE II) scores. According to the severity of the disease, the patients were divided into a mild HTG-AP group and a severe HTG-AP group. The changes of coagulation indexes (PT, APTT and FIB), D-dimer and C-reactive protein (CRP) levels were detected. Coagulation indexes, D-dimer level and disease severity (CRP level, APACHE II scores) were compared between the 2 groups. Spearman correlation analysis was used to analyze the correlation between the above indexes. Univariate and multivariate binary logistic regression analysis were used to identify the independent risk factors for severe HTG-AP. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of PT, FIB, and D-dimer for the severity of HTG-AP. RESULTS: There were significant differences in gender between the mild HTG-AP group and the severe HTG-AP group (P<0.05). There was no significant difference in age, recurrence rate and incidence of complications between the 2 groups (all P>0.05). The basic conditions of the 2 groups were similar and comparable. PT, FIB and D-dimer levels in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.001). There was no significant difference in APTT between the 2 groups (P>0.05). The CRP level and APACHE II scores in the severe HTG-AP group were significantly higher than those in the mild HTG-AP group (all P<0.05). Spearman correlation analysis showed that PT, FIB and D-dimer were positively correlated with CRP and APACHE II scores (all P<0.05), while APTT was not correlated with CRP and APACHE II scores (all P>0.05). Logistic regression analysis showed that prolonged PT and elevated D-dimer level were independent risk factors for severe HTG-AP (both P<0.05). ROC curve analysis showed that the AUC of PT for predicting severe HTG-AP was 0.764 (95% CI 0.690 to 0.837, P<0.001), when PT>14.40 s, the sensitivity, specificity, positive predictive value, and negative predictive value were 63.07%, 79.03%, 59.42%, and 80.00%, respectively. TheAUC of FIB for predicting severe HTG-AP was 0.669 (95% CI 0.588 to 0.751, P<0.001), when FIB>4.18 g/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 61.53%, 70.17%, 49.38%, and 76.85%, respectively. The AUC of D-dimer for predicting severe HTG-AP was 0.753 (95% CI 0.680 to 0.826, P<0.001), when D-dimer>1.28 μg/mL, the sensitivity, specificity, positive predictive value, and negative predictive value were 73.84%, 66.12%, 53.33%, and 82.82%, respectively. The AUC of PT combined with D-dimer for predicting severe HTG-AP was 0.797. CONCLUSION: There are abnormalities in coagulation and fibrinolytic system in patients with HTG-AP in the early stage. PT, FIB and D-dimer levels are increased with the aggravation of the AP, and have a positively correlation with it. Elevated PT and D-dimer level are independent risk factors for severe HTG-AP. PT combined with D-dimer may be a sensitive indicator for prediction of the severity of HTG-AP in early phase.
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