Increased Plasma Fibrinogen Levels Research Articles

Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection.

Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV+, TPV+ versus TPV- exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhigh monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

Associations between pesticide exposure with biomarkers of stroke risk factors in farmers.

The extensive use of pesticides may cause acute and chronic intoxication. Therefore, this study aimed to reveal the associations between pesticide exposure and serum markers for stroke risk factors in farmers. A cross-sectional study was conducted with farmers, who used chemical pesticides in Seloprojo Village, Ngablak District, Magelang Regency, Central Java Province, Indonesia. A questionnaire containing demographics, pesticide use, and aspects related to work was employed. Measurements of serum cholesterol, uric acid, glucose, cholinesterase, and fibrinogen levels were also conducted. Of the 106 subjects, 31 (29.2%) used organophosphates as chemical pesticides. There was a significant difference between organophosphate and nonorganophosphate groups in plasma fibrinogen levels. The organophosphate group had higher levels of fibrinogen (292.29 ± 67.56 mg/dL) than the non-organophosphate group (255.24 ± 38.90 mg/dL). Of the studied risk factors for stroke, there is a significant association between organophosphate exposure and increased plasma fibrinogen levels.

Emergency administration of fibrinogen concentrate for haemorrhage: systematic review and meta-analysis

IntroductionThe occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations.Methods and analysisIn this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials.ResultsNine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64–2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI − 0.99–0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07–5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment.ConclusionsThe present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.

Etiology of diarrhoea among adult buffaloes (Bubalus bubalis) and their impact on haemato-biochemical and mineral profile

80 adult buffaloes suffering from diarrhea from sub-tropical and temperate zones of Jammu division were selected to establish etiology and to evaluate hemato-biochemical and mineral alterations. Clinico-haemato-biochemical,mineral and faecal evaluation was carried to relate alterations with respect to etiologies of diarrhoea. Strongyle infection was recorded among 32.5% buffaloes followed by amphistomiasis (18.75%), coccidiosis (7.5%), salmonellosis (7.5%) and balantidiasis (7.5%). 23.45% of affected buffaloes were placed under miscellaneous group as definite etiology could not be established. Season-wise, analysis revealed maximum prevalence of diarrhoea during rainy season (47.5%) followed by summer (35%) and winter (17.5%). Animals of 1 to 3 years age group had higher prevalence of coccidiosis (50%), strongyle infection (46.1%) and salmonellosis (37.5%) whereas, >6 years age group had higher prevalence amphistomiasis (66.7%) and balantidiasis (50%). Significant reduction (P<0.05) in hemoglobin, TEC, TPP, albumin, sodium, chloride, calcium and copper levels was recorded along with significant increase in plasma fibrinogen level among the diarrheic buffaloes. The results of blood gas analysis revealed significant (P<0.05) decrease in pH, pCO2, HCO3 and base excess and significant (P<0.05) increase in anion gap. Since, diarrhoea is a multifactorial disease leading to varying clinical signs, haemato-biochemical, mineral and blood gas changes which needs to be evaluated before recommending therapeutic regimen for recovery.

Blood Viscosity in Subjects With Type 2 Diabetes Mellitus: Roles of Hyperglycemia and Elevated Plasma Fibrinogen.

The viscosity of blood is an indicator in the understanding and treatment of disease. An elevated blood viscosity has been demonstrated in patients with Type 2 Diabetes Mellitus (T2DM), which might represent a risk factor for cardiovascular complications. However, the roles of glycated hemoglobin (HbA1c) and plasma fibrinogen levels on the elevated blood viscosity in subjects with T2DM at different chronic glycemic conditions are still not clear. Here, we evaluate the relationship between the blood viscosity and HbA1c as well as plasma fibrinogen levels in patients with T2DM. The experimental data show that the mean values of the T2DM blood viscosity are higher in groups with higher HbA1c levels, but the correlation between the T2DM blood viscosity and the HbA1c level is not obvious. Instead, when we investigate the influence of plasma fibrinogen level on the blood viscosity in T2DM subjects, we find that the T2DM blood viscosity is significantly and positively correlated with the plasma fibrinogen level. Further, to probe the combined effects of multiple factors (including the HbA1c and plasma fibrinogen levels) on the altered blood viscosity in T2DM, we regroup the experimental data based on the T2DM blood viscosity values at both the low and high shear rates, and our results suggest that the influence of the elevated HbA1c level on blood viscosity is quite limited, although it is an important indicator of glycemic control in T2DM patients. Instead, the elevated blood hematocrit, the enhanced red blood cell (RBC) aggregation induced by the increased plasma fibrinogen level, and the reduced RBC deformation play key roles in the determination of blood viscosity in T2DM. Together, these experimental results are helpful in identifying the key determinants for the altered T2DM blood viscosity, which can be used in future studies of the hemorheological disturbances of T2DM patients.

Abstract 11207: Electronic Hookah Vaping with and Without Nicotine: Insights into Vascular Function and Plasma Fibrinogen

Introduction: Electronic nicotine delivery systems (ENDS) are growing quickly in the United States, particularly among youth. Electronic (e-) hookahs are a new category of vaping devices in which the e-bowl is combined with and placed on a traditional waterpipe, allowing the flavored aerosol to pass through a water-filled base before being carried through the hose into the user’s mouth. E-hookah vaping with flavored nicotine acutely impairs endothelial function. However, the relative contribution of flavorings vs. nicotine on e-hookah vaping associated vascular dysfunction is unclear. Methods: In a randomized cross-over design study, we investigated the acute effect of flavored e-hookah with and without nicotine and sham vaping, among a cohort of 9 healthy young adult chronic hookah smokers (27±1 years, mean ±SE), on endothelial function, measured by brachial artery flow-mediated dilation (FMD). Fibrinogen, a major plasma protein coagulation factor, as well as smoking exposure biomarkers (plasma nicotine and expired carbon monoxide levels) were collected before and after the sessions. Results: Vaping e-hookah with nicotine induced an acute reduction in FMD (from 6.9±0.9 to 5.2±0.8%, pre- vs. post- vaping, p<0.001), suggesting impairment in endothelial function and increased plasma fibrinogen (+14.5±4.1 mg/dL, p<0.001). Though vaping e-hookah in the absence of nicotine did not significantly impair endothelial function (p = ns), it significantly induced an increase in plasma fibrinogen levels (+20.9±7.4 mg/dL, p<0.001), higher than levels induced after vaping e-hookah with nicotine. Plasma nicotine concentrations increased 4-fold more after vaping e-hookah with nicotine, whereas no changes were observed after vaping e-hookah without nicotine or sham-vaping (p = ns). Exhaled CO levels did not change across all three vaping sessions. Conclusions: In healthy young adults, our findings to date suggest that while vaping e-hookah with nicotine induces an unfavorable effect on the vasculature, non-nicotine constituents generated from heating the flavored e-hookah aerosol cannot be ignored. Further plans are needed to elucidate the long-term vascular implications of vaping non-nicotine flavored constituents.

Assessment of plasma fibrinogen as a marker of diabetic nephropathy

Diabetes is one of the most common chronic hyperglycemic syndrome. Diabetic Nephropathy is one of the major complications of DM characterized by persistent albuminuria, increased arterial blood pressure, a relentless decline in glomerular filtration rate (GFR) & a high risk of cardiovascular morbidity & mortality. The biological marker of DN is fibrinogen. Fibrinogen, is increased in diabetic patients. An increase in plasma fibrinogen levels is also considered an independent risk factor for diabetic nephropathy. Fibrinogen is the major coagulation protein in blood.To find out whether the levels of Plasma Fibrinogen levels can be used as markers for the early diagnosis of DN.A case control study. The study includes total of 150 patients, of which 50 were diabetic without any complications, 50 were diabetic nephropathy patients and remaining 50 were age matched healthy controls. The mean plasma fibrinogen level in control group was 190.34 ± 72.83 mg/dl. The mean plasma fibrinogen levels in DM & DN groups were 522.76 ± 115.79 mg/dl & 657.64 ± 124.61 mg/dl respectively. In our study, fibrinogen levels were increased significantly in DM group compared to controls which was further increased in DN group. Hence above studies interpret that fibrinogen increases in diabetes with complications.Fibrinogen correlated positively with FBS, HbA, TC, triglyceride, LDL, Blood Urea, serum creatinine, TC/HDL, LDL/HDL & urine A/C ratio in both DM & DN group, whereas there was negative correlation of fibrinogen with HDL & eGFR. Thus fibrinogen could be used as early biomarkers for the diagnosis of DN.

Emergency administration of fibrinogen concentrate for hemorrhage: A protocol for systematic review and meta-analysis.

Introduction:The occurrence of massive hemorrhages in various emergency situations increases the need for blood transfusions and the risk of mortality. Use of fibrinogen concentrate (FC) may increase plasma fibrinogen levels more rapidly than the use of fresh-frozen product or cryoprecipitate. However, thus far, the efficacy of FC in significantly improving the risk of mortality and significantly reducing transfusion requirements has not been effectively demonstrated in several systematic reviews and meta-analyses.Methods and analysis:We will conduct a systematic review and meta-analysis of FC for hemorrhages in emergency situations. We will include controlled trials, but will exclude randomized controlled trials in elective surgeries. We will include patients with hemorrhages in emergency situations. Intervention will be emergency supplementation of FC. The control group will be administered with ordinal transfusion or placebo. The primary outcome of the study is in-hospital mortality.We will search in electronic databases such as MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers will independently screen the title and abstract, retrieve the full text of the selected articles, and extract the essential data. We will apply uniform criteria for evaluating the risk of bias associated with individual randomized controlled trial based on the Cochrane risk of bias tool. Values of the risk ratio will be expressed as a point estimate with 95% confidence intervals (CIs). Data of continuous variables will be expressed as the mean difference along with their 95% CIs and P values. We will assess the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and dissemination:This systematic review will provide physicians with updated information on the efficacy and safety of using FC for hemorrhage in emergency settings. Approval from the ethics board and patient consent were not required in our study.This study protocol has been funded through a protocol registry. The registry number is UMIN000041598.

Measurement of plasma fibrinogen and D-dimer in a sample of Iraqi patients with solid malignant tumors

Background: Multifactor affect the pathogenesis of thrombosis in solid malignancy; however, a significant role is attributed to the cancer cells ability to interact with and activate the host hemostatic system. [1] 
 Hemostasis is highly correlated to tumor growth, angiogenesis and metastasis, modulation of these pathways reflects interesting and promising treatment options in the future. [1]
 Most patients with cancer frequently suffer from chronic compensated DIC and have abnormal laboratory coagulation tests without clinical manifestations of thrombosis, which is a subclinical hypercoagulable state that can be detected by varying degrees of activation of blood clotting. The results of laboratory tests in these patients reflect continuous fibrin formation and lysis during the course of malignancy. [1]
 Aim of study: To study the effect of solid malignant tumors on blood coagulation via measurements of plasma fibrinogen and D-dimer.
 Subjects and methods: Thirty patients (9 males and 21 females) attending the oncology consultatory out-patient clinic at Baghdad Teaching Hospital/ Medical City were randomly selected and included in this study.
 These patients were newly diagnosed as having malignant solid tumors depending on histopathological reports from private and governmental sectors.
 All the laboratory tests were done at the hematology and biochemistry departments of Teaching Laboratories/ Medical City.
 Results: Plasma fibrinogen level was significantly higher in patients group rather than control group (3.863 ±0.706) Vs (2.497±0.457 g/L} respectively, (P-value 0.001).The mean value of factor VIII activity was {181% ±58.4)and (99.3% ±11.1)for patient and control groups respectively, the P-Value was significant ( > 0.001 ).D-dimer was negative for all members of control group, for patients group ( 66.7 %) of them showed positive D-dimer and (33.3)were negative for D-dimer ,P-value was significant ( >0.001 ). Conclusions: There was increase in plasma fibrinogen level and positive D-dimer in cancer patients compared to the control group reflecting subclinical thrombophilia and higher risk of VTE in patients with solid tumors due to activation of prothrombotic and fibrinolytic pathways by malignant cells which is vital for the use of primary prophylaxis by anticoagulants.

Cryoprecipitate transfusion in bleeding patients.

The management of acquired coagulopathy in multiple clinical settings frequently involves fibrinogen supplementation. Cryoprecipitate, a multidonor product, is widely used for the treatment of acquired hypofibrinogenemia following massive bleeding, but it has been associated with adverse events. We aimed to review the latest evidence on cryoprecipitate for treatment of bleeding. We conducted a narrative review of current literature on cryoprecipitate therapy, describing its history, formulations and preparation, and recommended dosing. We also reviewed guideline recommendations on the use of cryoprecipitate in bleeding situations and recent studies on its efficacy and safety. Cryoprecipitate has a relatively high fibrinogen content; however, as it is produced by pooling fresh frozen donor plasma, the fibrinogen content per unit can vary considerably. Current guidelines suggest that cryoprecipitate use should be limited to treating hypofibrinogenemia in patients with clinical bleeding. Until recently, cryoprecipitate was deemed unsuitable for pathogen reduction, and potential safety concerns and lack of standardized fibrinogen content have led to some professional bodies recommending that cryoprecipitate is only indicated for the treatment of bleeding and hypofibrinogenemia in perioperative settings where fibrinogen concentrate is not available. While cryoprecipitate is effective in increasing plasma fibrinogen levels, data on its clinical efficacy are limited. There is a lack of robust evidence to support the use of cryoprecipitate in bleeding patients, with few prospective, randomized clinical trials performed to date. Clinical trials in bleeding settings are needed to investigate the safety and efficacy of cryoprecipitate and to determine its optimal use and administration.

Progress in research on the role of fibrinogen in lung cancer.

Lung cancer is one of the most prevalent malignancies worldwide. Local recurrence and distant metastasis remain the major causes of treatment failure. It has been recognized that the process of tumor growth and metastasis involves multiple interactions between tumor and host. Various biomarkers have been used for predicting tumor recurrence, metastasis, and prognosis in patients with lung cancer. However, these biomarkers are still controversial and require further validation. The relationship between malignancy and coagulation system disorders has been explored for more than a century. Fibrinogen is the most abundant plasma coagulation factor synthesized mainly by hepatic cells. Increased plasma fibrinogen levels were observed in various carcinomas such as gastric cancer, colon cancer, and pancreatic cancer. Recent studies have also investigated the role of fibrinogen in patients with lung cancer. This review aimed to address the role of fibrinogen in lung cancer.

Скринінгова коагулограма при фізіологічному перебігу вагітності

The objective: to evaluate the performance of screening coagulation tests in normal pregnancy. Materials and methods. A study of screening coagulation tests was conducted with the participation of 124 patients with normal pregnancy in terms of 12–14, 20–22, 28–30 and 37–40 weeks of gestation. The control group consisted of 82 patients who were at the pregravid stage of pregnancy planning. Coagulation tests were determined on a HELENA 2000 coagulometer. Namely, the activated partial thromboplastin time, the percentage of prothrombin by Quick and fibrinogen were examined. Results. During normal pregnancy, a dynamic, statistically significant increase in plasma fibrinogen level was determined. This indicator during full-term pregnancy differed from that of non-pregnant women by 1.8 times. During all normal pregnancies, there was no statistically significant dynamics of the activated partial thromboplastin time and the percentage of prothrombin by Quick, but there was a tendency towards these indicators increase in coagulation potential with an increase in the gestation term. Conclusion. When assessing a screening coagulation tests, pregnancy term should be taken into account first of all, rather than comparing the obtained values with reference indices for non-pregnant women. Keywords: screening coagulation tests, hemostatic system, fibrinogen level, prothrombin percentage by Quick, activated partial thromboplastin time.

Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment.

Post-thrombotic intracerebral hemorrhage (ICH) is experienced by 6-8% of stroke patients and is associated with multiple factors, including acquired coagulopathy induced by the thrombolytic drug. The objective of this study was to assess the outcome of the intravenous (IV) administration of fibrinogen concentrate in a series of acute stroke patients who developed iatrogenic fibrinogen critical depletion after IV thrombolysis. Of the 39 ischemic stroke patients treated with IV thrombolysis with a severe hypofibrinogenemia requiring infusion with IV fibrinogen concentrate, 30 patients were treated with 2 g of IV recombinant tissue plasminogen activator (rt-PA), followed by further doses until the fibrinogen level reached 200 mg/dL in hemorrhagic patients or 100 mg/dL in non-hemorrhagic patients, and 9 were treated with IV rt-PA followed by endovascular thrombectomy. Preand post-thrombolysis National Institutes of Health Stroke Scale (NIHSS) scores were statistically different for the Cochran-Mantel-Haenszel test overall (p = 0.0002), at 24-hour evaluation (p = 0.0455) and at 7-day assessment (p = 0.0006). Within the first 7 days post-thrombolysis, the brain computed tomography (CT) scans showed that 20/39 (51.28%) patients had ICH. Of the whole sample, 25.6% of the ICH patients had symptomatic intracerebral hemorrhage (SICH), according to National Institute of Neurological Disorders and Stroke (NINDS) classification. After rt-PA treatment, the median pre-thrombolysis fibrinogenemia of 332 mg/dL significantly dropped to 133 mg/dL (p < 0.0001). After the fibrinogen concentrate infusion, the median level of fibrinogenemia rose to 160 mg/dL, which was significantly higher than the median postthrombolysis levels (p < 0.0001). Recanalization was observed in 25/28 patients (89.29%): complete in 18 and partial in 7 patients. After fibrinogen IV infusion, no thrombotic complications were seen in 37 out of 39 patients (94.77%); 2/39 (0.05%) patients experienced a pulmonary embolism, 1 of them a segmental one. This study showed the clinical safety of administering IV fibrinogen concentrate in order to increase plasma fibrinogen levels in a series of acute stroke patients with iatrogenic fibrinogen depletion after IV thrombolysis.

Significant genetic association of a functional TFPI variant with circulating fibrinogen levels and coronary artery disease.

The tissue factor pathway inhibitor (TFPI) gene encodes a protease inhibitor with a critical role in regulation of blood coagulation. Some genomic variants in TFPI were previously associated with plasma TFPI levels, however, it remains to be further determined whether TFPI variants are associated with other coagulation factors. In this study, we carried out a large population-based study with 2313 study subjects for blood coagulation data, including fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). We identified significant association of TFPI variant rs10931292 (a functional promoter variant with reduced transactivation) with increased plasma fibrinogen levels (P=0.017 under a recessive model), but not with PT, APTT or TT (P>0.05). Using a large case-control association study population with 4479 CAD patients and 3628 controls, we identified significant association between rs10931292 and CAD under a recessive model (OR 1.23, P=0.005). For the first time, we show that a TFPI variant is significantly associated with fibrinogen levels and risk of CAD. Our finding contributes significantly to the elucidation of the genetic basis and biological pathways responsible for fibrinogen levels and development of CAD.

Plasma fibrinogen level may be a possible marker for the clinical response and prognosis of patients with breast cancer receiving neoadjuvant chemotherapy.

Neoadjuvant chemotherapy has been established as standard treatments for advanced breast cancer among multidisciplinary therapies. A simple and instructive biomarker for the postoperative recurrence and metastasis is needed to evaluate the therapeutic effect. Plasma fibrinogen level has been shown to be associated with tumor progression and poor outcomes in breast cancer patients. This study aims to further evaluate the clinical and prognostic value of plasma fibrinogen level as a biomarker in breast cancer patients receiving neoadjuvant chemotherapy. In this study, data of 67 patients were retrospectively collected and analyzed to identify the relationship between the plasma fibrinogen level and the clinical progression and outcome of these patients. Patients with increased plasma fibrinogen level after neoadjuvant chemotherapy had significantly shorter disease-free survival and overall survival (p < 0.001 and p = 0.001, respectively). In a univariate survival analysis, molecular type (p = 0.0004/p = 0.005), clinical response (p = 0.008/p = 0.015), and changes in plasma fibrinogen level (p = 0.012/p = 0.007) were associated with disease-free survival and overall survival, and all of them, molecular type (p = 0.0003/p = 0.005), clinical response (p = 0.027/p = 0.021), and changes in plasma fibrinogen level (p = 0.035/p = 0.025), were associated with disease-free survival and overall survival in a multivariate survival analysis, respectively. The plasma fibrinogen level was found to be a possible biomarker for clinical response to chemotherapy and postoperative metastasis or death in advanced breast cancer patients who received neoadjuvant chemotherapy.

Clinical significance of coagulation factors in operable colorectal cancer.

Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28–84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D-dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper-fibrinogenemia (≥327 mg/dl), high D-dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D-dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.

Prognostic implications of plasma fibrinogen and serum Creactive protein levels in non-small cell lung cancer resection and survival

Purpose : To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein (CRP) levels in tumour resection and survival following successful tumour resection in patients with nonsmall cell lung cancer (NSCLC). Methods : One hundred and fifty-three NSCLC patients who underwent surgical resection at a tertiary care hospital from January 2006 through December 2010 were enrolled. Pre-operative serum CRP and plasma fibrinogen levels were measured. The levels of these biomarkers correlated with tumour size and pathologic TNM stage. The possibility of complete resection and associated findings are reported. Results : Plasma fibrinogen (r = 0.381, p = 0.002) and serum CRP (r = 0.471, p < 0.001) levels were positively associated with tumour diameter. Increased levels of these biomarkers were significantly associated with sex, smoking status, histological type, tumour stage, and clinical stage. Partial tumour resection occurred in 28 % (27/95) of patients with an increased plasma fibrinogen level compared to 10 % (6/58) with a normal fibrinogen level (p = 0.008), and in 30 % (29/97) of patients with an increased serum CRP level compared to 11 % (6/56) with a normal CRP level (p = 0.006). Patients with elevated CRP and fibrinogen concentrations demonstrated higher susceptibility to disease advancement and survival compared to patients with normal fibrinogen and CRP levels. Conclusion : Pre-operative functional concentrations of serum CRP and plasma fibrinogen could serve as indicators of tumour resectability wherein a high tumour resection rate is possible in patients with favourable pre-operative levels of these biomarkers. Increased concentrations of serum CRP and plasma fibrinogen are associated with poor overall survival and progression-free survival. Key words : Plasma fibrinogen, serum C-reactive protein, biomarker, non-small cell lung cancer

The effects of sildenafil citrate on some biochemical and hematological parameters in alloxan-induced diabetes (Type I) in male albino rats

Abstract Background: Sildenafil citrate is a phosphodiesterase type 5 (PDE5) inhibitor, which increases cyclic guanosine monophosphate (cGMP). It is well established that the pathogenesis of diabetic mellitus is associated with abnormalities of nitric oxide (NO) generation. Many of the biological actions of NO are mediated by cGMP, which is rapidly degraded by phosphodiesterases. Aim: The Aim of this study is to evaluate the effect of sildenafil citrate on some biochemical and hematological parameters in alloxan-induced diabetes in male albino rat. Methods: Diabetes was induced after an intraperitoneal (i.p.) injection of a single dose of alloxan (150 mg/kg body weight). Sildenafil was administered daily at a dose of (10 mg/kg body weigh) via oral gavages during a period of 14 days to normal healthy rats as well as diabetic rats. Blood samples were collected after 7 and 14 days of treatment in all experimental groups. Results: The present investigation showed that alloxan injection induced significant elevations in serum glucose level, the percent of glycohemoglobin (HbA1c) and serum malondialdehyed (MDA) level. Moreover, alloxan administration resulted in prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT), as well as increase in plasma fibrinogen level. Meanwhile, protein C and protein S concentrations were significantly decreased due to alloxan treatment. Oral administration of sildenafil to diabetic rats improved most diabetic complications including hyperglycemia, oxidative stress, hemoglycation and hyperfibrinogenemia induced by alloxan. The modulatory effects of sildenafil obtained herein were partial, but significant and more pronounced when administered for14 days. In addition, sildenafil administration to normal healthy rats was found to have no effect on the studied parameters. Conclusion: The present study showed that sildenafil may have beneficial effects against some diabetic complications. The mechanism by which sildenafil citrate exerts its effect on the studied parameters might be attributed to increased cGMP which is brought out by its phosphodiesterase inhibitory action and this is discussed in details.

Increased fibrinogen levels at diagnosis are associated with adverse outcome in patients with acute myeloid leukemia

Increased plasma fibrinogen levels are associated with shortened overall survival (OS) in some solid tumor types. In contrast, the prognostic significance of varying fibrinogen levels in acute myeloid leukemia (AML) at diagnosis is unknown. In this study, we assessed the prognostic significance of fibrinogen levels in AML patients. In a comprehensive retrospective single-center study, we determined the survival rates of 375 consecutive AML patients undergoing at least one cycle of intensive chemotherapy induction treatment. Patients were dichotomized between low (<4.1 g/L) and high fibrinogen levels (≥4.1 g/L) at diagnosis of AML before initiation of treatment. Subsequently, quartile ranges were applied to analyze the association of varying fibrinogen levels on survival. We observed that the rates of complete remission, early death, and admission to intensive care unit were equal in the low versus high fibrinogen group. However, OS was significantly better in the low fibrinogen group (27.3 vs 13.5 months; p = 0.0009) as well as progression-free survival (12.3 vs 7.8 months; p = 0.0076). This survival difference remained significant in the multivariate analysis (p = 0.003). Assessing quartiles of fibrinogen values, we further confirmed this observation. Our data suggest that high fibrinogen levels at diagnosis of AML are associated with unfavorable OS and progression-free survival but not with increased mortality during induction treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Preoperative Plasma Fibrinogen Level as a Significant Prognostic Factor in Patients With Localized Renal Cell Carcinoma After Surgical Treatment.

We sought to investigate the association of preoperative fibrinogen levels with clinicopathologic outcomes after surgical treatment of nonmetastatic renal cell carcinoma. We reviewed the records of 1511 patients who had their fibrinogen levels measured preceding surgery. The associations between preoperative fibrinogen level and risk of adverse clinicopathologic outcomes were tested using the multivariate logistic regression and multiple Cox-proportional hazards model, respectively.Based on plasma fibrinogen levels, we stratified the patients into 2 groups with a cut-off value of 328 mg/dL. Kaplan–Meier analysis showed significantly inferior survival outcomes in progression-free (P < 0.001), cancer-specific (P < 0.001), and overall survival (P < 0.001). In multivariate analyses, a high fibrinogen level (≥328 mg/dL) was significantly related to a higher Fuhrman grade (hazard ratio [HR] 1.374, P = 0.006) and a larger tumor size (≥7 cm) (HR 2.364, P < 0.001). Multivariate Cox analysis also revealed that a high preoperative fibrinogen level is a significant predictor for poor disease progression (HR 1.857, P < 0.001), cancer-specific survival (HR 3.608, P = 0.003), and overall survival (HR 1.647, P = 0.027).Increased plasma fibrinogen levels were significantly associated with poor pathological features and worse survival outcomes in patients with nonmetastatic renal cell carcinoma after surgical treatment. Further evaluations such as prospective randomized trials are needed to understand the underlying mechanism for these associations.