Elevated Plasma Fibrinogen Levels Research Articles

High levels of plasma fibrinogen are related to post-stroke cognitive impairment.

IntroductionStudies have shown that high levels of the fibrinogen (FIB) are related to cognitive deficits. However, the relationship between fibrinogen and cognitive deficit after stroke remains unclear. Therefore, we explored the relationship between plasma fibrinogen and post‐stroke cognitive impairment (PSCI).MethodsThis study is carried out in the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. A total of 210 patients with acute ischemic stroke were enrolled in this study. Ultimately, 134 patients completed 3‐month follow‐up. Blood samples were collected at hospital admission. Cognitive function was evaluated 3 months after stroke. All patients underwent the Mini‐Mental State Examination (MMSE) after 3 months.ResultsHigher levels of fibrinogen were observed in patients with post‐stroke cognitive impairment compared with the non‐PSCI group (p < .001). Additionally, elevated plasma fibrinogen levels were independently associated with PSCI (odds ratio [OR] = 2.000, 95% CI 1.062–3.770 p = .032). The plasma fibrinogen levels were negatively correlated with the 3‐month MMSE scores (r = −.171, p = .048). In a multivariate linear regression, FIB was negatively associated with the 3‐month MMSE scores after adjustment for the other variables (β = −0.782, p = .035).ConclusionHigh levels of plasma fibrinogen were associated with the presence and severity of PSCI.

Systemic immune-inflammation index, serum albumin, and fibrinogen impact prognosis in castration-resistant prostate cancer patients treated with first-line docetaxel.

To evaluate the prognostic value of pretreatment plasma systemic immune-inflammation index (SII), albumin, and fibrinogen levels in metastatic castration-resistant prostate cancer (mCRPC) patients treated with first-line docetaxel and to screen out the patients with the greatest risk for poor prognosis. The plasma SII, albumin, and fibrinogen levels were examined before treatment and analyzed with patient clinicopathological parameters and overall survival (OS). The survival analysis was performed using the Kaplan-Meier method, and prognostic factors were assessed using the Cox proportional hazard regression model. The incidences of elevated SII level, hypoproteinemia, and hyperfibrinogenemia were 52.51%, 25.14%, and 27.93%, respectively. SII level was associated with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (P < 0.001). Albumin level was found closely correlated with ECOG PS (P = 0.006), PLR (P = 0.042), and hemoglobin (P = 0.009), but not other parameters. Elevated plasma fibrinogen level was significantly associated with Eastern Cooperative Oncology Group performance status (ECOG PS) (P = 0.009), visceral metastases (P < 0.001), and PLR (P = 0.001). In multivariate Cox regression model, visceral metastases SII (HR 2.133, 95% CI 1.163-3.913; P = 0.014), albumin (HR 0.540, 95% CI 0.307-0.949; P = 0.032), and fibrinogen (HR 1.888, 95% CI 1.069-3.335; P = 0.029) were further confirmed to be the independent prognostic factors for OS. Of the three target parameters, we found that patients with none abnormalities of the three parameters showed the best prognosis, and patients with at least any two abnormalities of them showed markedly worse prognosis than patients with any one abnormalities of the three parameters (P < 0.001). Pretreatment SII, albumin, and fibrinogen are independent prognostic factors in mCRPC patients treated with first-line docetaxel. Moreover, the combined use of SII, albumin, and fibrinogen levels may help us to identify the high-risk populations for treatment decisions.

Preoperative predictors of early death risk in bladder cancer patients treated with robot-assisted radical cystectomy.

BackgroundEarly identification of early death for bladder cancer patients undergoing radical cystectomy based on the laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for bladder cancer patients.MethodsA total of 186 bladder cancer patients who underwent robot‐assisted radical cystectomy (RARC) were identified between October 2014 and May 2017. The probability of dying within 1 year after RARC was defined as the end point “early death.” Predictive factors including clinical features and laboratory findings at diagnosis were retrospectively collected.ResultsMedian follow‐up time after RARC was 20.6 months (1.2‐43.7 months). Fifty‐one patients (27.4%) died during follow‐up and 31 within 1 year from surgery (1‐year mortality rate: 16.7%). All potentially prognostic factors were assessed on univariate analyses, which revealed the following factors as being associated with higher risk of early death within 1 year after RARC: older age (P = 0.004), advanced clinical stage (P = 0.005), presence of hydronephrosis (P = 0.021), higher fibrinogen (P = 0.007), higher PLR (P = 0.031), and lower PNI (P = 0.016). In a multivariate Cox proportional hazard regression model analysis, age >60 years (HR = 7.303, 95% CI 1.734‐30.764; P = 0.007) and fibrinogen ≥3.295 g/L (HR = 2.396, 95% CI 1.138‐5.045; P = 0.007) at diagnosis were independent prognostic factors of early death after RARC.ConclusionAge and preoperative elevated plasma fibrinogen level were independent predictors for 1‐year mortality after RARC. We believe that plasma fibrinogen levels may become a useful biomarker, which may help guide the treatment decision‐making process for patients with bladder cancer.

Prognostic value of plasma fibrinogen in hepatocellular carcinoma: a meta-analysis

BackgroundElevated plasma fibrinogen levels have been associated with tumor progression in several malignancies. Our study aims to characterize the clinical significance of elevated plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC).Materials and methodsRelevant published articles were systematically searched in electronic databases including PubMed, Embase, and Web of Science. The pooled differences in plasma fibrinogen levels among HCC, cirrhotic, and control groups were expressed as weighted mean differences (WMDs) and their corresponding 95% CIs. The associations between elevated fibrinogen and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) were expressed as HRs and their 95% CIs, whereas the associations between elevated fibrinogen and various types of clinical characteristic of patients with HCC were expressed as ORs and their corresponding 95% CIs.ResultsResults showed that the plasma fibrinogen levels in patients with HCC were not significantly different than that in healthy controls (WMD = 0.50, 95% CI = [−0.82, 1.82], P = 0.457) or patients with cirrhosis (WMD = −0.62, 95% CI = [−1.56, 0.33], P = 0.200). However, our results showed that compared to those with normal levels, patients with HCC and elevated plasma fibrinogen levels showed poorer OS (HR = 2.08, 95% CI = [1.67, 2.59], P < 0.0001) and DFS/RFS (HR = 1.90, 95% CI = [1.52, 2.37], P < 0.0001). Results of trial sequential analysis of the OS indicated that currently available studies were sufficient to validate the negative prognostic value of elevated plasma fibrinogen in patients with HCC. Clinicopathological analyses showed that high plasma fibrinogen levels were associated with tumor progression as indicated by advanced tumor stage, larger tumor size, increased tumor number, and the presence of vascular invasion.ConclusionElevated plasma fibrinogen levels are associated with poor prognosis and advanced tumor progression. Plasma fibrinogen may serve as a negative prognostic biomarker in patients with HCC.

Platelet membrane receptor P2Y12 H1/H2 polymorphism is highly associated with cerebral infarction: a case-control study.

ObjectivesThis study aimed to determine the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in a Han population in North Shandong Province, People’s Republic of China.Patients and methodsA case–control study, which involved 168 nonstoke subjects (contrast group) and 152 CI patients (CI group), was conducted. The state of subjects in the CI group was validated by computed tomography or MRI. The clinical data were categorized into two groups. The data included age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were genotyped with PCR and restriction fragment length polymorphism analysis. The distribution characteristics of nonstoke subjects and CI patients and the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke were analyzed.ResultsNo significant difference was found between the contrast group and CI group (P>0.05) in terms of age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low-density protein, high-density lipoprotein cholesterol, uric acid and homocysteine. In contrast, significant differences were found between these two groups (P<0.01) in terms of SBP, DBP and plasma fibrinogen level. The genotyping revealed 112 carriers of the wild-type H1/H1 genotype and 40 carriers of the mutational H2 allele of P2Y12 H1/H2 in the CI group and 140 carriers of the wild-type H1/H1 genotype and 28 carriers of the mutational H2 allele of P2Y12 H1/H2 in the contrast group. Furthermore, the H1/H2 and H2/H2 gene frequencies (26.3%) were significantly higher in the CI group (χ2=4.440, P<0.05) than those in the contrast group (16.7%). Moreover, the frequencies of the H2 allele in the CI and contrast groups were 14.5% and 8.6%, respectively, and the difference was statistically significant (χ2=5.392, P<0.05). Multiple logistic regression analysis results revealed that factors associated with CI include systolic blood pressure and plasma fibrinogen level, which carry the −893T gene. After adjusting for potential confounding factors, the H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928, 95% confidence interval: 1.137–3.188; P=0.038) when compared with noncarriers.ConclusionThe present study found that hypertension and elevated plasma fibrinogen levels are significant risk factors for ischemic stroke and confirmed that the H1/H2 and H2/H2 genes of platelet membrane glycoprotein receptor P2Y12 are risk factors of ischemic stroke.

Quantitative Proteomic Approach Targeted to Fibrinogen β Chain in Tissue Gastric Carcinoma.

Elevated plasma fibrinogen levels and tumor progression in patients with gastric cancer (GC) have been largely reported. However, distinct fibrinogen chains and domains have different effects on coagulation, inflammation, and angiogenesis. The aim of this study was to characterize fibrinogen β chain (FGB) in GC tissues. Retrospectively we analyzed the data of matched pairs of normal (N) and malignant tissues (T) of 28 consecutive patients with GC at diagnosis by combining one- and two-dimensional electrophoresis (1DE and 2DE) with immunoblotting and mass spectrometry together with two-dimensional difference in gel electrophoresis (2D-DIGE). 1DE showed bands of the intact FGB at 50 kDa and the cleaved forms containing the fragment D at ~37–40 kDa, which corresponded to 19 spots in 2DE. In particular, spot 402 at ~50 kDa and spots 526 and 548 at ~37 kDa were of interest by showing an increased expression in tumor tissues. A higher content of spot 402 was associated with stomach antrum, while spots 526 and 548 amounts correlated with corpus and high platelet count (>208 × 109/L). The quantification of FGB and cleaved products may help to further characterize the interconnections between GC and platelet/coagulation pathways.

Elevated plasma fibrinogen levels in multiple sclerosis patients during relapse

Fibrinogen is a protein that plays a key role in blood coagulation and thrombosis and it is involved in several inflammatory processes; in multiple sclerosis (MS) may be related with blood-brain barrier (BBB) disruption. We analysed the relationship between plasma fibrinogen levels and the presence of active lesions on magnetic resonance imaging (MRI) during relapses of multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients. MethodsWe collected data of patients admitted to a tertiary-care hospital with relapse of MS and CIS from 2008 to 2013 and we analysed the relation between plasma fibrinogen levels (normal: 200mg/dl-417mg/dl) and the presence of active lesions on brain or spinal MRI. ResultsA total of 58 patients were included, 45 (77%) CIS patients, 12 (21%) relapsing-remitting MS (RR-MS) and 1 (2%) active progressive MS (P-MS). 17 patients had high plasma fibrinogen levels (> 417mg/dl). Among total of patients with elevated plasma fibrinogen, 15 (88%) had active lesions on MRI and only 2 (12%) did not have active lesion on MRI (p = 0,013) with a specificity of 95%. All patients with fibrinogen > 417mg/dl were CIS (p = < 0.05). Discussion: We observed that high plasma fibrinogen levels had a high specificity high specificity, but low sensitivity (only 40%) for detection of active lesions on MRI during relapses of MS. These findings support the hypothesis that fibrinogen could play an important role on the development of MS lesions, however, additional studies are needed to confirm these results.

Effect of captopril and enalapril on selected coagulation markers in hyperlipidemia

Background: In addition to their primary indications, hypertension and congestive heart failure, angiotensin converting enzyme inhibitors, ACE-Is, have pleiotropic effects, which are under active investigations. There is growing evidence of data stating the significant role of ACE-Is in the regulation of hemostasis.Objectives: The present study aimed to evaluate the effect of ACEIs on coagulation in hyperlipidemia.Materials and Methods: Twenty-eight male Sprague-Dawely rats aged 17-19 weeks were enrolled in this study. The animals were randomized into four groups each containg seven rats: group1, 2,3 and 4. Group 1 was fed a standard chow diet and serve as normal diet control while group 2,3 and 4 received atherogenic diet (4% cholesterol-enriched diet) for eight weeks. Animals in group 2, 3 and 4 were treated with distilled water (lipidemic control), captopril and enalapril for the next four weeks respectively. Captopril was used in a dose of 2x25 mg/kg/day P.O. Enalapril was given in a dose of 15 mg /kg/day P.O. At the end of the experiment, the animals were sacrified and blood sample was obtained from the heart for determination of prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma fibrinogen, platelets count and total serum cholesterol (TSC).Results: Hyperlipidemia is associated with significant rise in plasma fibrinogen level (p&lt;0.05). Captopril and enalapril treatment showed significant fall in elevated plasma fibrinogen levels (p&lt;0.05). Hyperlipidemic rats treated with captopril and enalapril for 4 weeks showed significant prolongation of PT and aPTT ( p&lt;0.05) while the platelets counts were statistically unaffected ( p&gt;0.05).Conclusion: We conclude that captopril and enalapril possess favorable effect on coagulation in hyperlipidemia.

Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis.

ObjectiveTo evaluate the effect of elevated plasma fibrinogen levels on the prognosis of epithelial ovarian cancer (EOC).MethodsWe reviewed the data of 217 patients with advanced-stage EOC between 2000 and 2012, and investigated the prognostic role of elevated plasma fibrinogen levels compared with serum CA-125 levels, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). For further evaluation, we performed a meta-analysis using 5 cohort studies published to July 2015, including our cohort study after a literature review.ResultsAmong the four biomarkers, only plasma fibrinogen levels >485.2 mg/dL were correlated with impaired progression-free survival (PFS) and overall survival (OS) (median, 13.9 vs. 20.3 months and 42.2 vs. 55.4 months; p<0.010). Elevated plasma fibrinogen levels were an independent factor for poor PFS with marginal significance and OS (adjusted hazard ratios [HRs]=1.389 and 1.581; 95% confidence intervals [CIs]=0.979–1.972 and 1.032–2.423, respectively). Furthermore, crude and subgroup meta-analyses demonstrated that elevated plasma fibrinogen levels were associated with impaired PFS and OS in patients with all stage EOC.ConclusionElevated plasma fibrinogen levels be more important for predicting survival than serum CA-125 levels, NLR and PLR in patients with EOC, in particular, advanced-stage disease. Moreover, it may be related to poor prognosis of EOC.

Natural Remedies Lower Elevated Fibrinogen Levels in the Prevention of Atherosclerosis

Cardiovascular Disease (CVD), which includes heart attack and stroke, is the number one cause of death in the United States. Data gathered from certain lab tests utilized as part of an early detection and prevention strategy can be used to gauge the efficacy of preventative measures in an effort to halt or slow the progression of CVD. Acute phase reactant tests, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Fibrinogen, and Ferritin are the most clinically relevant to detection. Acute phase reactants are proteins that increase or decrease in the presence of inflammatory stimuli. Of the four tests, the most widely used in conventional medicine are ESR and CRP. Fibrinogen tests are underutilized in conventional medicine. Fibrinogen, which originates in the liver, is a fibrous glycoprotein in vertebrates that helps in the formation of blood clots. Fibrinogen levels rise in the following conditions: Inflammation, tissue damage/trauma, infection, cancer, acute coronary syndrome, strokes, and inflammatory diseases. Fibrinogen tests are often used after a cardiovascular incident has occurred or if symptoms are severe enough to warrant a test. However, there is sufficient evidence which shows that fibrinogen levels slowly begin to rise long before a heart attack or stroke and may even be reflective of the severity of subclinical atherosclerotic conditions. Traditional Chinese Medicine (TCM) and other preventative natural medical systems have treatments which reduce or normalize Fibrinogen levels, thereby, preventing the progression of symptoms that can lead to more serious cardiovascular occurrences in the future. This article will review published studies that show how natural remedies can effectively lower elevated plasma fibrinogen levels.

Prognostic value of preoperative plasma fibrinogen level and platelet-to-lymphocyte ratio (F-PLR) in patients with localized upper tract urothelial carcinoma.

PurposeHemostatic factors is thought to have a potentially significant role in progression and metastasis of malignant tumors. We investigated the prognostic value of preoperative plasma fibrinogen level and platelet-to-lymphocyte ratio (PLR) in localized upper tract urothelial carcinoma (UTUC).Materials and MethodsA total of 481 patients who underwent radical nephroureterectomy for localized UTUC (pTa-4N0M0) were identified between January 2002 and June 2013. Patients were assigned a F-PLR score of 0, 1, or 2 based upon the presence of elevated plasma fibrinogen level, an elevated PLR, or both. The association between F-PLR score and clinicopathological variables was analysed.ResultsThe optimal cut-off value of plasma fibrinogen and PLR for overall survival stratification was determined to be 4.22 and 241.2. Kaplan–Meier analysis revealed significant differences in cancer specific survival (CSS) and overall survival (OS) among patients with F–PLR scores of 0, 1 and 2. Multivariate analysis identified higher F–PLR score as an independent risk factor for CSS (P < 0.001) and OS (P < 0.001). The estimated c-index of the multivariate model for CSS and OS increased from 0.772 and 0.756 to 0.799 and 0.784 when F–PLR score added, which was higher than fibrinogen level, PLR or neutrophil-to-lymphocyte ratio added.ConclusionsPreoperative F-PLR score is a negative independent prognostic factor for survival outcomes in patients with localized upper tract urothelial carcinoma. Preoperative F-PLR score may become a useful biomarker, particularly because of its low associated cost and easy accessibility.

Elevated preoperative plasma fibrinogen level is an independent predictor of malignancy and advanced stage disease in patients with bladder urothelial tumors

PurposeTo investigate the association between preoperative plasma fibrinogen levels and clinicopathological features in patients with bladder urothelial tumors. MethodsIn this retrospective single-center study, we evaluated preoperative plasma fibrinogen levels in 503 patients newly diagnosed with bladder urothelial tumors between January 2009 and October 2014. All patients received surgical intervention as the primary treatment method. Associations between preoperative plasma fibrinogen levels and clinicopathological parameters were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent associations. ResultsThe mean preoperative fibrinogen level in patients with bladder urothelial carcinoma (BUC) was significantly higher than that in patients with papilloma or papillary urothelial neoplasm of low malignant potential (PUNLMP) (P = 0.004). Additionally, patients with BUC with advanced-stage disease showed elevated plasma fibrinogen levels compared to patients with early-stage disease (high-grade BUC vs. low-grade BUC: P = 0.002; muscle-invasive BUC vs. non-muscle-invasive BUC: P = 0.010). In a multivariate regression model, a plasma fibrinogen level >3.04 g/L was identified to be independently associated with the presence of BUC (hazard ratio [HR] = 1.653, P = 0.047), high-grade BUC (HR = 1.869, P = 0.004), and muscle-invasive BUC (HR = 1.870, P = 0.044). ConclusionsElevated preoperative plasma fibrinogen level is an independent predictor of malignancy as well as advanced-stage carcinoma in patients with bladder urothelial tumors, suggesting that plasma fibrinogen may be a promising diagnostic and prognostic biomarker for bladder tumors.

Can Prediction of Functional Outcome after Stroke Be Improved by Adding Fibrinogen to Prognostic Model?

Several studies demonstrated that elevated plasma fibrinogen level is associated with poor functional outcome after ischemic stroke. It remains, however, unclear if prediction of functional outcome after stroke can be improved by adding fibrinogen to prognostic model. We aimed to determine the prognostic value of plasma fibrinogen for the prediction of functional outcome after ischemic stroke. We retrospectively analyzed the data of 727 ischemic stroke patients (median age: 70; 48% men). The functional outcome was assessed 1 month after stroke onset using modified Rankin Scale. Unfavorable outcome was defined as modified Rankin Scale score higher than 2. Using C-statistic and reclassification measures (net reclassification improvement-NRI and integrated discrimination improvement-IDI), we compared the predictive abilities of 2 models. The first model contained stroke severity and age, and the second one included fibrinogen in addition. After adjusting for age and stroke severity, plasma fibrinogen level higher than 2.95 g/L was associated with unfavorable outcome (OR: 1.80, 95% CI: 1.20-2.72, P < .01). The addition of fibrinogen did not lead to an improvement in predictive ability of the model. C-statistic did not differ between models (.90 versus .90, P = .34). The categorical NRI was .01 (P = .66) and the IDI was .006 (P = .08). The addition of fibrinogen to predictive model including age and stroke severity does not improve discrimination between favorable and unfavorable outcomes after ischemic stroke.

Inflammation and Progression of CKD: The CRIC Study.

CKD is a global public health problem with significant mortality and morbidity. We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants. Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of ≥50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-α and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P<0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P<0.01), and TNF-α (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P<0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P<0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P<0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P<0.001), and TNF-α (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P<0.001) with outcome were attenuated but remained significant. Elevated plasma levels of fibrinogen and TNF-α and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.

Elevated plasma fibrinogen level shows superior prognostic value than Epstein-Barr virus DNA load for stage IVA/B nasopharyngeal carcinoma patients in the intensity-modulated radiotherapy era

PurposeEffective prognostic factors for patients with stage IVA/B nasopharyngeal carcinoma (NPC) who are susceptible to distant metastases are limited. We aim to investigate the prognostic value of pretreatment plasma fibrinogen (FIB) level and Epstein–Barr virus DNA (EBV-DNA) load in these patients in the era of intensity-modulated radiotherapy (IMRT).ResultsThe 5-year DSS, DFS and DMFS rates of the entire cohort were 72.7%, 66.8%, 80.0%, respectively. High FIB level was identified as a negative prognostic factor for survival: the 5-year DSS, DFS and DMFS rates for patients with high FIB (> 4.0 g/L) and normal FIB (≤ 4.0 g/L) were 60.3% vs. 76.0%, 56.0% vs. 69.9%, and 59.4% vs. 85.5%, respectively (all P < 0.001). Subgroup analysis demonstrated that DSS, DFS and DMFS decreased as FIB gradually increased, even within the normal range. The risk of distant metastasis in patients with high FIB was over 3-fold than patients with normal FIB. EBV-DNA was not an independent prognostic factor for any survival outcomes in multivariate analysis.ConclusionHigh pretreatment FIB level shows superior prognostic value than EBV-DNA load for stage IVA/B NPC patients in the era of IMRT.Materials and MethodsA total of 755 patients with newly-diagnosed stage IVA/B NPC treated with definitive IMRT between January 2007 and December 2011 were enrolled. Plasma FIB and EBV-DNA were measured before treatment. Disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method; differences were compared using the log-rank test.

Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors.

Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.

An elevated preoperative plasma fibrinogen level is associated with poor overall survival in Chinese gastric cancer patients

ObjectiveTo investigate the association between preoperative plasma fibrinogen level and overall survival (OS) in a cohort of Chinese gastric cancer patients who underwent gastrectomy. MethodsA retrospective cohort study was conducted among 1090 gastric cancer patients treated between January 2003 and December 2011 who were eligible for inclusion criteria. Plasma fibrinogen level was routinely measured before surgeries. The optional cut-off value for fibrinogen level was estimated by receiver operating characteristic (ROC) curve analysis. OS was evaluated using Kaplan-Meier curve. Univariate and multivariate Cox regression models were performed to determine correlations between preoperative plasma fibrinogen level and OS. ResultsEnrolled subjects who returned for at least one follow-up visit had been followed for a median of 44.0 months (interquartile range, 62.0 months). An optimal cut-off value of 3.9g/L was determined for preoperative plasma fibrinogen level. Lymph node dissection method, tumor location, invasion depth, lymph node metastasis, differentiation, distant metastasis, CA199 and plasma fibrinogen level remained statistically significant with OS in multivariate analysis. Plasma fibrinogen level was significantly associated with age, tumor size, lymph node dissection method, invasion depth, lymph node metastasis, TNM stage and CEA. ConclusionsElevated preoperative plasma fibrinogen was independently associated with poor prognosis and may serve as a clinically useful biomarker for risk assessment and treatment choice in Chinese gastric cancer patients.

Pretransplant Elevated Plasma Fibrinogen Level is a Novel Prognostic Predictor for Hepatocellular Carcinoma Recurrence and Patient Survival Following Liver Transplantation.

Elevated plasma fibrinogen is associated with tumour progression and poor outcomes in several cancers. The present study investigated the prognostic value of preoperative fibrinogen in hepatocellular carcinoma (HCC) patients after liver transplantation (LT). We analyzed the preoperative plasma fibrinogen levels of 41 patients who underwent LT for HCC. The cut-off value for elevated level of fibrinogen was determined by using a receiver operating characteristic (ROC) curve analysis. Cox regression analysis was performed to analyze the relationship between elevated fibrinogen level and HCC recurrence. The disease-free survival (DFS) and overall survival (OS) rate after transplantation were calculated by Kaplan-Meier method and compared by log-rank test. The fibrinogen levels were significantly higher in patients with tumor recurrence (3.31±0.98 g/L) compared with those in patients without recurrence (2.39±0.89 g/L) (P<0.01). A cut-off value for elevated fibrinogen level of 2.675 g/L was defined. Cox regression analysis showed that the relative risk for tumor recurrence increased by 6.871 times for patients with elevated fibrinogen. Eleven patients in the elevated fibrinogen group (21 cases) developed recurrence, while only 2 in the normal fibrinogen group (20 cases) developed recurrence. There were significant differences in DFS and OS between the elevated fibrinogen group and normal fibrinogen group (5-year DFS and OS of 44.0% and 42.9% vs. 89.2% and 80.0%, respectively, P<0.05). Vascular invasion and fibrinogen level ≥2.675 g/L were the independent prognostic predictors of tumor recurrence and poor outcome. Pretransplant elevated fibrinogen levels are associated with tumor recurrence and poor prognosis in hepatocellular carcinoma patients after liver transplantation.

Plasma fibrinogen level: an independent prognostic factor for disease-free survival and cancer-specific survival in patients with localised renal cell carcinoma.

To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC). We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment.

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer.

PurposeElevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.MethodsTwo hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.ResultsElevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.ConclusionsThis study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.