利用凝固曲线分析与手工法检测快速识别1例Fibrinogen Longmont

Fibrinogen Longmont是异常纤维蛋白原血症中比较独特的一种,既往常因光学法异常而磁珠法正常的检测结果被发现。通过一个案例我们观察到Fibrinogen Longmont患者的凝固曲线与典型的低纤维蛋白原血浆凝固曲线存在明显区别:手工法检测可明显观测到凝块的透明特性;样本血浆与正常血浆的混合实验也出现明显的抑制效应。这些实验室表现可能有助于Fibrinogen Longmont的筛查。

Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer

BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.

Fibrinogen在术前肾癌患者血清中水平变化及临床意义

目的:探讨肾癌患者术前血浆Fibrinogen水平与临床病理特征及患者预后的关系。方法:选取2000年1月至2003年12月天津医科大学附属肿瘤医院泌尿肿瘤科患者286例为研究对象。术前常规测定所有患者血浆Fibrinogen水平,t检验或ANOVA分析术前血浆Fibrinogen水平与多个临床病理特征相关性,并进一步通过单因素分析及Cox回归模型对预后影响因子进行分析结果:术前血浆Fibrinogen水平与Fuhrman分级、肿瘤大小、T分期及术后远处转移密切相关(均P<0.001)。单因素结果显示,Fuhrman分级、肿瘤大小、T分期及术前血浆Fibrinogen水平与患者总生存时间显著相关(P<0.001,P=0.001,P<0.001,P<0.001)。进一步通过Cox回归模型分析发现,术前血浆Fibrinogen水平是肾癌术后患者的一个独立预后因子(P=0.001)。结论:术前血浆Fibrinogen水平与肾癌术后患者远处转移及预后显著相关,是肾癌术后患者的一个独立预后因子。

牙鲆fibrinogen β基因的克隆及表达分析

通过mRNA差异显示发现一个鳗弧菌刺激后在牙鲆肝脏中表达量显著增加的片段,结合RACE技术得到了该差异片段1 856 bp的全长cDNA,包含一个1 479 bp的开放阅读框,编码的蛋白质含有fibrinogenβ的C末端签名序列。同源性分析表明其氨基酸序列与鱼类以及哺乳类的fibrinogenβ都具有高度的相似性,因此可断定此基因为牙鲆的fibrinogenβ基因(GenBank登录号为EF581895)。RT-PCR分析表明,在注射鳗弧菌后,该基因在肝脏、肾脏、脾脏、腮、肠、心脏中的表达量呈现逐渐增加的趋势。推测其可能在鳗弧菌侵染中,起到了促进伤口愈合的作用,或通过和其他细胞因子结合在防御细菌的侵染中发挥免疫调节作用。

Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients

AIM To investigate the prognostic role of fibrinogen-toalbumin ratio(FAR) on patients with gallbladder cancer(Gbc) in this study.METHODS One hundred and fifty-four Gbc patients were retro-spectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve(ROc curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses.RESULTS ROc curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age(P = 0.045), jaundice(P < 0.001), differentiation(P = 0.002), resection margin status(P < 0.001), T stage(P < 0.001), TNM stage(P < 0.001), and c A199(P < 0.001) as well as albumin levels(P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio(HR): 2.343, 95% confidence interval(c I): 1.532-3.581, P < 0.001], TNM stage(P = 0.035), albumin level(HR = 0.595, 95%c I: 0.385-0.921, P = 0.020) and FAR(HR: 2.813, 95%c I: 1.765-4.484, P < 0.001) were independent prognostic factors in Gbc patients.CONCLUSION An elevated preoperative FAR was significantly correlated with unfavorable overall survival in Gbc patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with Gbc. The preoperative FAR could be used to predict the prognosis of Gbc patients, which was easily accessible, costeffective and noninvasive.

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma(GBC).METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic(ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0.RESULTS ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival(OS)(HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735(for preoperative plasma fibrinogen only) and 0.729(for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199(P < 0.001), resection margin(P < 0.001) and TNM stage(P = 0.010) were independent prognostic factors for GBC.CONCLUSION The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

Prognostic significance of preoperative fibrinogen in patients with colon cancer

AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients.

Platelets in hemostasis and thrombosis:Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.

Dynamic changes in fibrinogen levels of patients with acute cerebral infarction after taking defibrase

BACKGROUND： At present, as a therapeutic drug mainly for reducing fibrinogen （FIB） levels, the dynamic influence of defibrase on the FIB levels of patients with acute cerebral infarction has not been clearly ascertained. OBJECTIVE： To observe the dynamic changes in FIB levels of patients with acute cerebral infarction at different time points after taking defibrase. DESIGN, TIME AND SETTING： Randomized controlled clinical trial. The study was conducted in the Department of Neurology, the Second Affiliated Hospital of Jinan University, from June to November 2006. PARTICIPANTS： Sixty patients with acute cerebral infarction, who had been treated by the Neurological Department of the Second Affiliated Hospital of Jinan University from June to November 2006, were selected, including 37 males and 23 females, aged 35-75 years. All cases met the diagnostic criteria formulated by the Fourth National Cerebrovascular Disease Conference within 12 hours of onset. All the patients were confirmed with definite hemiparesis and cerebral infarction without coma, and were randomly divided into two groups： a treatment group （n =40） and a control group （n =20）. Patients＇ families had the right to be informed and agree with the treatment, which had permission from the Hospital Ethics Committee. METHODS： Patients in the control group were given routine treatment with 30 mL fleabane and 0.75 g cytidine diphosphate added to 500 mL saline solution once a day for 14 consecutive days. Patients in the treatment group were given routine treatment and Haiwang defibrase injection （purchased from Changchu Guoao Bio-Pharmaceutical Co. Ltd., Approval document number H10983237） within 12 hours of infarction. Defibrase doses of 15, 12.5 and 10 U were given over 2 hours according to the patients＇ pre-treatment plasma FIB levels of ≥ 4.50 g/L, 3.50 4.49 g/L and 1.00 3.49 g/L, respectively. Plasma FIB levels in the treatment group were measured before, and once every six hours for 48 hours after administration of defibrase. Later, measurements were taken once every 12 hours and FIB levels were kept in a range of 0.5-1.3 g/L for one week. When the FIB level increased to over 1.3 g/L, a 5 U dose of defibrase was given again over two hours, FIB levels of the control group were measured once before treatment and once after one week of treatment MAIN OUTCOME MEASURES： （1） Dynamic changes of FIB levels in the defibrase treatment group. （2） Comparison of dynamic changes of FIB levels in the treatment group and control group before and after treatment for one week. RESULTS： All 60 patients were included in the final analysis. The treatment group＇s FIB levels quickly decreased to 0.5-1.3 g/L within 12 hours of taking the first dose of defibrase and reached a minimum in 24 hours. Later, they began to rise slowly into the therapeutic range （0.5-1.3 g/L） in 48 hours. The FIB levels of the treatment group increased slowly to over 1.3 g/L in 60 hours after the first dose of defibrase and then quickly decreased to the therapeutic range after the second dose of 5 U defibrase with a minimum level higher than after the first dose, and higher again after the third dose. After treatment, patients＇ FIB levels could be kept in the therapeutic range for about one week. The FIB levels in patients in the treatment group were significantly lower after taking defibrase for one week in comparison with the levels before treatment （P 〈 0.01）. There was no difference in the control group between the levels pre-treatment and one week after treatment （P 〉 0.05）. CONCLUSIONS： FIB levels in patients with acute cerebral infarction quickly decrease after taking the first dose of defibrase and reach a minimum in 24 hours. Later, they begin to rise slowly into the therapeutic range （0.5-1.3 g/L） in 48 hours. The FIB levels increase slowly to over 1.3 g/L in 60 hours. The effect of defibrase is weaker when the same dose of defibrase is used in patients repeatedly.

Prognostic value of fibrinogen and D-dimer-fibrinogen ratio in resectable gastrointestinal stromal tumors

AIM To investigate the prognostic value of preoperative fbri-nogen concentration （FIB） and D-dimer-fibrinogen ratio （DFR） in gastrointestinal stromal tumors （GISTs）.METHODS The purpose of this study was to retrospectively ana-lyze 170 patients with GISTs who were admitted to our hospital from January 2010 to December 2015. The op-timal cutoff values of related parameters were estimated by receiver operating characteristic （ROC） curve analysis. The recurrence free survival （RFS） rate was evaluated using Kaplan-Meier curves. Univariate analysis and multivariate Cox regression models were used to analyze the prognostic factors of GISTs. The relationship between the FIB, D-dimer, DFR, platelet count （PLT）, and the clinicopathological features of GISTs was described by the chi-square test or nonparametric rank sum test （Mann-Whitney test）.RESULTS In ROC analysis, the optimal cutoff values of FIB, D-dimer, DFR, and PLT were 3.24 g/L, 1.24 mg/L, 0.354, and 197.5 （× 109/L）, respectively. Univariate analysis and the Kaplan-Meier survival curve showed that FIB, D-dimer, DFR, PLT,National Institutes of Health （NIH） risk category, tumor size, tumor location, and mitotic index were signifcantly relevant to the 3-year and 5-year survival rate of patients （ P 〈 0.05）. Cox multivariate regression analysis illustrated that FIB （RR： 0.108, 95%CI： 0.031-0.373）, DFR （RR： 0.319, 95%CI： 0.131-0.777）, and NIH risk category （ RR： 0.166, 95%CI： 0.047-0.589） were independent prognostic factors of the RFS rate （ P 〈 0. 05）. Moreover, FIB, D-dimer, DFR, and PLT were correlated with the clinical features of GISTs.CONCLUSIONFIB, D-dimer, DFR, and PLT are all related to the prognosis of GISTs. Moreover, FIB and DFR may be independent risk factors for predicting the prognosis of resectable GISTs.

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer

Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival.In this study,we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio(NLR)in predicting the survival of patients with non-small cell lung cancer(NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery.The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators,including the combination of fibrinogen and NLR(F-NLR).The cut-off values for fibrinogen,NLR,and clinical laboratory variables were defined by the receiver operating characteristic(ROC)curve analysis.According to the ROC curve,the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30,respectively.Patients with both a high NLR(≥2.30)and hyperfibrinogenemia(≥3.48 g/L)were given a score of 2,whereas those with one or neither were scored as 1 or 0,respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival(DFS)[hazard ratio(HR),1.466;95%confidence interval(CI),1.243–1.730;P<0.001]and overall survival(OS)(HR,1.512;95%CI,1.283–1.783;P<0.001).The five-year OS rates were 66.1%,53.5%,and 33.3%for the F-NLR=0,F-NLR=1,and F-NLR=2,respectively(P<0.001).Correspondingly,their five-year DFS rates were 62.2%,50.3%,and 30.4%,respectively(P<0.001).In the subgroup analyses of the pathological stages,the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers.Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

Thrombocytopenia in cirrhosis:Impact of fibrinogen on bleeding risk

AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA retrospective analysis of our OLT Database (2006-2015) was performed. Baseline haematological indices and intraoperative blood transfusion requirements, as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood, was noted as a surrogate for intraoperative bleeding. Two groups: Excessive transfusion (> 1200 mL returned) and No excessive transfusion ( RESULTSOf 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of P ≤ 0.001), platelet count (P = 0.005), clauss fibrinogen (P = 0.004) and heparinase MA (P = 0.001) were all statistically significantly different. Univariate logistic regression with a cut-off of platelets 9/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393 (95%CI: 0.758-2.563; P = 0.286). Review of receiver operating characteristic curves showed an area under the curve (AUC) for platelet count of 0.604 (95%CI: 0.534-0.675; P = 0.005) as compared with AUC for fibrinogen level, 0.678 (95%CI: 0.612-0.744; P ≤ 0.001). A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease (P = 0.006), Hb (P = 0.022) and Fibrinogen (P = 0.026) to be statistically significant, whereas Platelet count was not statistically significant. CONCLUSIONPlatelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.

Hypofibrinogenemia Caused by Hemocoagulase Injection:A Retrospective Study on Clinical Laboratory Findings

Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders.This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods Wie retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1,2015 to March 31,2018.Clinical data were collected and investigated,including clinical manifestations,hemostatic and fibrinolytic parameters,dosage of hemocoagulase,the medication time,and the cryoprecipitate blood product infusion.Differences in fibrinogen,D-dimer,and fibrin/fibrinogen degradation products(FDP)before,during,and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment(F=1.80,P<0.001),with the average decrease of 2.28 g/L(0.63-3.9 g/L).After withdrawal,fibrinogen level increased significantly compared to that during the medication(F=l.20,P<0.001),but was still lower than that before the medication(F=0.59,P=0.03).The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication(F=0.83,P=0.002;Wilcoxon-test,Z=-4.54,P<0.001).Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemo coagulase(r=-0.17,P=0.40;r=-0.28,P=0.15;respectively)and the time of recovery from hypofibrinogenemia(r=-0.45,P=0.05;r=0.13,P=0.61;respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection.Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

Elevated fibrinogen plasma level is not an independent predictor of poor prognosis in a large cohort of Western patients undergoing surgery for colorectal cancer

AIM To evaluate the clinical significance of the preoperative fibrinogen plasma level as a prognostic marker after surgery for colorectal cancer.METHODS This retrospective study analysed 652 patients undergoing surgery for stage Ⅰ-Ⅳ colorectal cancer between January 2005 and December 2012, at the Division of General Surgery A, University of Verona Hospital Trust, in whom preoperative fibrinogen plasma values were assessed at baseline. Fibrinogen is involved in tumourigenesis as well as tumour progression in several malignancies. Correlations between preoperative plasma fibrinogen values and clinicopathological characteristics were investigated. Univariate and multivariate survival analyses were performed to identify factors associated with overall and tumour-related survival.RESULTS Among the 652 patients, the fibrinogen value was higher than the threshold of 400 mg/dL in 345 patients(53%). The preoperative mean ± SD of fibrinogen was 426.2 ± 23.2 mg/dL(median: 409 mg/dL; range: 143-1045 mg/d L). Preoperative fibrinogen values correlated with age(P = 0.003), completeness of tumour resection, potentially curative vs palliative(P < 0.001), presence of systemic metastasis(P < 0.001), depth of tumour invasion p T(P < 0.001), nodes involvement p N(P = 0.001) and CEA serum level(P < 0.001). The mean fibrinogen value(± SD) was 395.6 ± 120.4 mg/d L in G1 tumours, 424.1 ± 121.4 mg/dL in G2 tumours and 453.4 ± 131.6 mg/dL in G3 tumours(P = 0.045). The overall survival and tumourrelated survival were significantly higher in patients with fibrinogen values ≤ 400 mg/d L(P < 0.001). However, hyperfibrinogenemia did not retain statistical significance regarding either overall(P = 0.313) or tumour-related survival(P = 0.355) after controlling for other risk factors in a multivariate analysis.CONCLUSION Preoperative fibrinogen levels correlate with cancer severity but do not help in predicting patient prognosis after colorectal cancer surgery.

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury

BACKGROUND: There have been few reports on the clinical significance of the fibrinogen degradation product(FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical signifi cance of the FDP level.METHODS: From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups: a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/m L, and a FDP≤100 group.RESULTS: The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score(ISS), volume of transfusion and mortality ratio in the FDP>100 group were signifi cantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS(R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency.CONCLUSION: The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

CORRELATION BETWEEN FIBRINOGEN LEVEL AND CEREBRAL INFARCTION

Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI. Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method. Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95%CI: 1.51-4.04, P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI(OR=4.34,95% CI:1.80-10.51, P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR=4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.

β-FIBRINOGEN PROMOTER -455 G/A(HaeIII)POLYMORPHISM PREDICTION OF PLASMA FIBRINOGEN BUT NOT OF ISCHEMIC CEREBROVASCULAR DISEASE

Objective The -455 G/A(HaeIII)polymorphism of β-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of ischemic cerebrovascular disease. Methods We accumulated 134 acute ischemic cerebrovascular disease(ICVD)cases and compared their -455 G/A status with a control group(n = 166). The β-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeIII. Results Plasma fibrinogen was higher in AA homozygous participants(341 mg/dL)than in partici-pants carrying the G allele: GA(290 mg/dL), GG(298 mg/dL)in the control group. Plasma fibrinogen was also higher in AA homozygous patients(353 mg/dL)than in cases carrying the G allele: GA(287 mg/dL), GG(302 mg/dL)in the ICVD group. However, there was no significant association between β-fibrinogen gene -455 G/A polymorphism and ICVD group. Conclusions Although a small effect cannot be excluded, β-fibrinogen gene -455 G/A polymor-phism is an independent predictor of plasma fibrinogen, but not of ischemic cerebrovascular disease.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUND Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity.Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system.Both indicators have been verified to have predictive value in the overall survival(OS)of many patients with solid malignancies.AIM To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma(PDAC)patients undergoing radical R0 resection.METHODS We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital,Chinese Academy of Medical Sciences,between January 2010 and December 2019.The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration.Enrolled patients were further divided into the any-high group(high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration)and the low-low group(low preoperative fibrinogen and D-dimer concentrations)according to the optimal cutoff values.RESULTS The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L,respectively.Furthermore,multivariate Cox regression analysis showed that the preoperative fibrinogen concentration(HR:1.603,95%CI:1.201-2.140,P=0.001)and preoperative D-dimer concentration(HR:1.355,95%CI:1.019-1.801,P=0.036)exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection.A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer.The median OS duration of the low-low group(31.17 mo)was significantly longer than that of the any-high group(15.43 mo).Additionally,multivariate Cox regression analysis revealed that the degree of differentiation(P<0.001),lymph node metastasis(HR:0.663,95%CI:0.497-0.883,P=0.005),preoperative CA19-9 level(HR:1.699,95%CI:1.258-2.293,P=0.001),adjuvant therapy(HR:1.582,95%CI:1.202-2.081,P=0.001)and preoperative combined grouping(HR:2.397,95%CI:1.723-3.335,P<0.001)were independent predictors of OS in PDAC patients undergoing radical R0 resection.CONCLUSION Preoperative fibrinogen combined with D-dimer plays a predictive role in OS,and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Congenital dysfibrinogenemia misdiagnosed and inappropriately treated as acute fatty liver in pregnancy:A case report and review of literature

BACKGROUND The purpose of this study was to report the rare case of a pregnant woman with congenital dysfibrinogenemia(CD)misdiagnosed as acute fatty liver.She was treated according to the principles of acute fatty liver but achieved good clinical results.CASE SUMMARY A 30-year-old woman presented with 39(6/7)wk of menopause and 6 h of irregular abdominal pain and attended our hospital.Emergency surgery was performed due to fetal distress.Postoperative management followed the treatment principle of acute fatty liver.DNA sequencing was carried out on the pregnant woman and her pedigree.Coagulation values of the patient on admission were prothrombin time 33.7 s,activated partial thromboplastin time 60.4 s,thrombin time 45.2 s,and fibrinogen 0.60 g/L.DNA sequencing results showed that the woman carried a pathogenic heterozygous variation of the fibrinogen alpha chain gene(FGA),which is closely related to hereditary fibrinogen abnormality,and the mutation site was located in p.R350H.After a follow-up period of 12 mo,the mother and her newborn had a good prognosis without bleeding or thrombosis.CONCLUSION Pregnant women with CD may have atypical symptoms,which can easily lead to misdiagnosis.In addition,treatment can be attempted according to the principles of acute fatty liver management.This rare pregnant patient with CD was caused by a novel FGA(p.R350H)gene mutation.

Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODSFibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTSThere was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSIONThese data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage.