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Sample records for plasma fibrinogen level

  1. Association between plasma fibrinogen levels and mortality in acute-on-chronic hepatitis B liver failure.

    PubMed

    Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672-0.820, P < 0.001), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094-0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients.

  2. Plasma fibrinogen levels are correlated with postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma.

    PubMed

    Zhang, Danhong; Zhou, Xia; Bao, Wuan; Chen, Ying; Cheng, Lei; Qiu, Guoqin; Sheng, Liming; Ji, Yongling; Du, Xianghui

    2015-11-10

    This study investigated the correlation of preoperative plasma fibrinogen level with distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). A total of 255 patients with ESCC who underwent surgery in Zhejiang cancer hospital (Hangzhou, China), between October 2006 and December 2009, were evaluated in this retrospective study. Population controls were selected from a pool of cancer-free subjects in the same region. Each patient and cancer-free people provided 3-mL pretreatment blood. Plasma fibrinogen level was measured by the Clauss method. The effects of hyperfibrinogenemia on locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. The proportion of hyperfibrinogenemia was higher in ESCC patients than those in controls (40.4% vs 13.6%). Subjects with hyperfibrinogenemia had a significantly higher risk of ESCC than those with normal plasma fibrinogen level (adjust OR = 4.61; 95% CI = 3.02-7.01, P < 0.001) after adjusted for age, sex and smoking status. The Kaplan-Meier curves showed that patients with hyperfibrinogenemia had worse DMFS, RFS and OS (P < 0.001). Tumor length, lymph node metastasis and plasma fibrinogen level were independent prognostic factors of ESCC (P < 0.05). Increased plasma fibrinogen level was significantly associated with elevated risk of ESCC. Preoperative plasma fibrinogen level was a predictor of distant metastasis and independently associated with prognosis of patients with ESCC.

  3. Plasma fibrinogen concentration in a Chinese population.

    PubMed

    Ko, G T; Yeung, V T; Chan, J C; Chow, C C; Li, J K; So, W Y; Tsang, L W; Cockram, C S

    1997-06-01

    Plasma fibrinogen concentration has been shown to be a predictor of major cardiovascular events. Information on plasma fibrinogen amongst Chinese has been scanty. We examined the relationships between plasma fibrinogen concentration and cardiovascular risk factors in 988 chinese subjects who underwent 75 g oral glucose tolerance test for screening for glucose intolerance. The study involved a selected sample with subjects who had an history of gestational diabetes, delivery of big babies (birth weight > or = 4 kg), equivocal plasma glucose concentrations and subjects who were family members of diabetic patients. This was mainly a non-smoking (96.6%), non-drinking (98%) and non-exercising (99%) population of which 87% (n = 855) were female. Among the 988 subjects (age +/- S.D. 36.8 +/- 10.2, range 16-79 years), plasma fibrinogen concentration ranged from 1.40 to 9.90 g/l with a mean of 3.26 +/- 0.93 g/l. On stratification of the subjects into 4 quartiles based on plasma fibrinogen concentrations, we found that increased plasma fibrinogen was associated with older age, higher body mass index (BMI), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose (PG), prevalence of diabetes, glycated haemoglobin (HbA1c) and triglyceride (TG) level. After adjustment for age and sex, increased plasma fibrinogen concentration remained associated with higher BMI, systolic BP, 2 h PG and TG level. On multivariate analysis using age, BMI, BP, TG, HbA1c and PG as independent variables, plasma fibrinogen was independently related to plasma TG concentration and HbA1c. With 1 S.D. change in TG concentration and HbA1c, there were 3.7 and 5.2% changes in plasma fibrinogen concentration respectively. These findings emphasize the close relationships between plasma fibrinogen and cardiovascular risk factors, in particular abnormal lipid and glucose metabolism.

  4. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    PubMed

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  5. The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer.

    PubMed

    Wang, Haiyan; Gao, Jinbiao; Bai, Ming; Liu, Rui; Li, Hongli; Deng, Ting; Zhou, Likun; Han, Rubing; Ge, Shaohua; Huang, Dingzhi; Ba, Yi

    2014-01-01

    Cancer patients frequently present with activated coagulation pathways and thrombocytosis, which are potentially associated with tumor progression and prognosis. However, the prognostic value of abnormal plasma fibrinogen and platelet levels for the treatment of pancreatic cancer is unclear. The purpose of our study was to evaluate the prognostic value of plasma fibrinogen and platelet levels in pancreatic cancer, and to devise a prognostic model to identify the patients with greatest risk for a poor overall survival. One hundred and twenty-five patients diagnosed with pancreatic ductal adenocarcinoma in our hospital between May 2000 and June 2005 were included in this study. The plasma fibrinogen and platelet levels were examined before treatment and analyzed along with patient clinicopathological parameters and overall survival. The foundation of prognostic model was based on the risk factors according to the Cox proportional hazard model. The incidence of hyperfibrinogenemia and thrombocytosis was 24.8% (31/125) and 15.2% (19/125), respectively. The mean fibrinogen concentration differed significantly between the early (I/II) and late (III/IV) stage patients (3.19 ± 0.70 vs. 3.65 ± 0.90 g/l, p = 0.008). Patients with a higher concentration of plasma fibrinogen and platelets had a worse prognosis (p < 0.05). There also existed a significant correlation between higher fibrinogen/platelet levels and distant organ metastasis (p < 0.05, respectively). Bivariate correlation analysis showed that plasma fibrinogen levels correlated significantly with platelet levels (p = 0.000). Multivariate analysis revealed that pretreatment plasma fibrinogen levels (p = 0.027), tumor stage (p = 0.026) and distant metastasis (p = 0.027) were independent prognostic factors. The median survival time for the low-, intermediate-, and high-risk groups was 9.6 months (95% CI 6.2-13.0), 3.8 months (95% CI 2.3-5.3), and 2.3 months (95% CI 0

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

    PubMed

    Lee, Hakmin; Lee, Sang Eun; Byun, Seok-Soo; Kim, Hyeon Hoe; Kwak, Cheol; Hong, Sung Kyu

    2016-01-01

    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.

  7. Fibrinogen and IL6 Gene Variants and IL-6 Levels in Relation to Plasma Fibrinogen Concentration and Cardiovascular Disease Risk in the Cardiovascular Health Study

    PubMed Central

    Carty, CL; Heagerty, P; Heckbert, SR; Jarvik, GP; Lange, LA; Cushman, M; Tracy, RP; Reiner, AP

    2009-01-01

    Summary Background: The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) in relation to CVD risk is not well-studied in humans. Methods and Results: We investigated joint associations of common fibrinogen and IL6 tagSNPs with fibrinogen level, carotid intima-media thickness (IMT) and risk of myocardial infarction (MI) or ischemic stroke in 3900 European-American participants of the Cardiovascular Health Study. To identify combinations of genetic main effects and interactions associated with each outcome, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were associated with fibrinogen level (p<0.005), but not with IMT (p>0.30), MI (p=0.73) or stroke (p=0.21). Fibrinogen levels were higher in higher in individuals having FGB1437 (rs1800790) minor alleles and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p=0.03) interactions between IL-6 level and SNPs located in promoter regions of FGA and FGG associated with fibrinogen levels were detected. Conclusion: We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD risk. PMID:20059469

  8. The estimation of fibrinogen levels in animal plasmas by a simple refractometric method. A comparison with a biuret method.

    PubMed

    Sutton, R H

    1977-05-01

    A comparison was made between a biuret (reference) method and a simple refractometric (test) method for measuring fibrinogen levels in 84 animal plasmas. Although the correlation between the two methods was high (4=0.90 P less than 0-001) there was considerable random variation in the refractometric results in relation to the biuret results. This was thought to be due in part to the fact that refractometric results could only be expressed in multiples of 2.4 g/litre. In spite of this limitation, the refractometric method, on the grounds of speen and simplicity, is considered to have worthwhile application for fibrinogen determinations in practice laboratory.

  9. Oil fly ash-induced elevation of plasma fibrinogen levels in rats.

    PubMed

    Gardner, S Y; Lehmann, J R; Costa, D L

    2000-07-01

    Particulate matter air pollution (PM) has been associated with morbidity and mortality from ischemic heart disease and stroke in humans. It has been hypothesized that alveolar inflammation, resulting from exposure to PM, may induce a state of blood hypercoagulability, triggering cardiovascular events in susceptible individuals. Previous studies in our laboratory have demonstrated acute lung injury with alveolar inflammation in rats following exposure to residual oil fly ash (ROFA), an emission source particulate. In addition, increased mortality has been documented following exposure to ROFA in rats with preexistent cardiopulmonary disease. ROFA's toxicity derives from its soluble metal content, which appears also to drive the toxicity of ambient PM. The present study was conducted to test the hypothesis that exposure of rats to a toxic PM, like ROFA, would adversely alter hemostatic parameters and cardiovascular risk factors thought to be involved in human epidemiologic findings. Sixty-day-old male Sprague-Dawley rats were exposed by intratracheal instillation (IT) to varying doses (0.3, 1. 7, or 8.3 mg/kg) of ROFA, 8.3 mg/kg Mt. Saint Helen's volcanic ash (MSH, control particle), or 0.3 ml saline (SAL, control). At 24 h post-IT, activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrinogen (PF), plasma viscosity (PV), and complete blood count (CBC) were performed on venous blood samples. No differences from control were detected in APTT and PT in ROFA-exposed rats; however, ROFA exposure did result in elevated PF, at 8.3 mg/kg only. In addition, PV values were elevated in both ROFA and MSH-exposed rats relative to SAL-control rats, but not significantly. Although no changes were detected in APTT and PT, alteration of important hematologic parameters (notably fibrinogen) through PM induction of an inflammatory response may serve as biomarkers of cardiovascular risk in susceptible individuals.

  10. Influence of heparin on fibrinogen and D-dimer plasma levels in acute myocardial infarction treated with streptokinase.

    PubMed

    Salvioni, A; Marenzi, G C; Agostoni, P; Grazi, S; Guazzi, M D

    1994-05-01

    The purpose of this study was to investigate whether, to what extent, and through which mechanisms intravenous heparin, administered before and after streptokinase, affects the plasma levels of D-dimer and fibrinogen in myocardial infarction. Data concerning mortality and incidence of coronary recanalization in patients receiving heparin and thrombolytic therapy after acute myocardial infarction are controversial; furthermore, the mechanisms through which heparin acts in combination with thrombolytic therapy are unclear. Thirty-eight patients with acute myocardial infarction treated with streptokinase were considered. Nineteen of them received, immediately before the beginning of thrombolytic treatment, a bolus of heparin (100 U.kg-1 intravenously) and, 2 h later, intravenous heparin in doses raising the partial thromboplastin time to 2-2.5 times the normal value (Group 1); the remaining 19 did not receive anticoagulant treatment (Group 2). Multiple determinations of plasma D-dimer and fibrinogen levels were obtained in all patients before, and in the seven days following thrombolytic treatment. Six hours after streptokinase, fibrinogen decreased from 304 +/- 34 to 61 +/- 34 mg.dl-1 in Group 1 and from 312 +/- 29 to 38 +/- 21 mg.dl-1 in Group 2 (P < 0.02 versus Group 1). The same difference between groups persisted at the 12th and at the 18th hour. D-dimer values, from 0.5 +/- 0.1 microgram.dl-1 in Group 1 and 0.4 +/- 0.1 microgram.dl-1 in Group 2, increased at the 1st hour to 37.2 +/- 36.5 micrograms.dl-1 and 52.2 +/- 39.8 micrograms.dl-1, respectively. A peak value was reached in both groups at the 6th hour, which was followed by a slow decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. High levels of plasma malondialdehyde, protein carbonyl, and fibrinogen have prognostic potential to predict poor outcomes in patients with diabetic foot wounds: a preliminary communication.

    PubMed

    Rattan, Roma; Nayak, Debashish

    2008-12-01

    Diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation and is generally known to have poor prognosis. Oxidative stress is considered important in the pathogenesis of chronic wounds. Fibrinogen is a recognized marker in peripheral vascular disease; increasing levels predict an increased mortality and risk of amputation. The aim of this study was to evaluate if plasma malondialdehyde (MDA), protein carbonyl (PC) and fibrinogen levels can be used as prognostic markers in patients with DFU. The study design was prospective, nonrandomized, and controlled. A total of 41 DFU grade 1 and 20 DFU grade 2 patients were studied in this case-control study. Diabetic controls without foot ulcers and healthy controls were also studied. Plasma MDA, PC, and fibrinogen levels were significantly higher in patients with DFU compared with those without ulcers (P < .05) and nondiabetic controls (P < .001). These parameters increased in association with DFU grade (P < .01). Increased levels of plasma fibrinogen, MDA, and PC correlated with worsened outcomes. An augmented oxidative stress and plasma fibrinogen level >300.4 mg% (95% confidence interval, 100% sensitivity, 99.2% specificity) was correlated with a high risk of amputation in DFU.

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

    PubMed Central

    Pedrazzani, Corrado; Mantovani, Guido; Salvagno, Gian Luca; Baldiotti, Elisabeth; Ruzzenente, Andrea; Iacono, Calogero; Lippi, Giuseppe; Guglielmi, Alfredo

    2016-01-01

    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/dL). 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 pT (P < 0.001), nodes involvement pN (P = 0.001) and CEA serum level (P < 0.001). The mean fibrinogen value (± SD) was 395.6 ± 120.4 mg/dL 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 tumour-related survival were significantly higher in patients with fibrinogen values ≤ 400 mg/dL (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. PMID:28018106

  13. Correlates of plasma fibrinogen (FG) levels in a random sample of community-dwelling elderly.

    PubMed

    Kostka, Tomasz; Para, Jadwiga; Kostka, Barbara

    2008-01-01

    The aim of this study was to evaluate the association between plasma FG levels and coexisting cardiovascular diseases (CVD) risk factors, comorbidities, functional status and cognitive function in a random sample of 270 (163 women and 107 men) community-dwelling elderly aged 65-79 years. The assessment included demographic and social variables, health status, nutritional state, physical and cognitive function. Physical activity was assessed by the Stanford Usual Activity Questionnaire. The average plasma FG level was lower in men 3.1+/-0.9 g/l (+/-SD) than in women 3.6+/-1.1g/l. In the whole group of elderly people, body mass index (BMI), percentage of body fat, calf circumference as well as total and low density cholesterol were positively correlated with FG levels, whereas the Stanford Moderate Index-negatively. Multifactor analysis of variance (ANOVA) revealed that female gender, calf circumference and the Stanford Moderate Index are the factors that independently predict FG levels. In conclusion, FG seems not to be related to functional status or cognitive function of older individuals. Nevertheless, our findings suggest that female gender, excess body fatness and low physical activity have an independent contribution to higher plasma FG levels in community-dwelling older subjects.

  14. Significant inverse association of marine n-3 fatty acids with plasma fibrinogen levels in Japanese in Japan but not in whites or Japanese Americans.

    PubMed

    Hassen, L J; Ueshima, H; Curb, J D; Choo, J; Lee, S; Masaki, K; Kadowaki, T; Shin, C; Evans, R W; Seto, T B; Fujiyoshi, A; Willcox, B J; Sutton-Tyrrell, K; Kadota, A; El-Saed, A; Miura, K; Kuller, L H; Sekikawa, A

    2012-03-01

    Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain. In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, USA, 302 Japanese in Kusatsu, Japan and 229 Japanese Americans in Honolulu, Hawaii, USA), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association. White, Japanese and Japanese-American men had mean marine n-3 FAs levels of 3.47%, 8.78% and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, P=0.049), after adjusting for age, body-mass index and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese-American men did not show a significant association. We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.

  15. The effect of repeated freezing and thawing on levels of vitamin K-dependent coagulation factors and fibrinogen in fresh frozen plasma

    PubMed Central

    Philip, Joseph; Sarkar, R. S.; Pathak, Amardeep

    2013-01-01

    Background: Fresh frozen plasma (FFP) is considered adequate for transfusion immediately after thawing or for up to 24 hours if kept at 1–6°C, and is currently used very often to replace deficient clotting factors. If factor levels in refrozen FFP are within normal limits, then this component can possibly be transfused, thus avoiding wastage of FFP. Aim: To study the fate of vitamin K-dependent coagulation factors (F II, F VII, F IX, F X) and fibrinogen activity levels in repeatedly (twice) frozen and thawed FFP. Materials and Methods: Two hundred FFP units comprising 50 units of each major blood group (A, B, AB, and O) were thawed at 37°C and 10–20 mL of FFP transferred to transfer bags with the help of a sterile connecting device (SCD). The FFP samples were taken into tubes (first sampling), and then the transfer bags were kept for 24 hours at 4°C. After 24 hours, repeat samples were taken in tubes from the transfer bag (second sampling), and then the bags were re-stored at < -18°C. One week later, the above procedure was repeated. Activity of coagulation factors and fibrinogen levels were measured by the automated coagulation analyzer. Results: The levels of F II, F VII, F IX, F X, and fibrinogen of all the 200 FFP units, at all four time points, were above the lower normal value, but well within the normal range. Conclusion: The levels of F II, F VII, F IX, F X, and fibrinogen remain stable and adequate for transfusion in twice-thawed-and-refrozen FFP. This component can be safely used for transfusion as a source of vitamin K-dependent clotting factors and fibrinogen. PMID:23559757

  16. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.

    PubMed

    Huffman, Jennifer E; de Vries, Paul S; Morrison, Alanna C; Sabater-Lleal, Maria; Kacprowski, Tim; Auer, Paul L; Brody, Jennifer A; Chasman, Daniel I; Chen, Ming-Huei; Guo, Xiuqing; Lin, Li-An; Marioni, Riccardo E; Müller-Nurasyid, Martina; Yanek, Lisa R; Pankratz, Nathan; Grove, Megan L; de Maat, Moniek P M; Cushman, Mary; Wiggins, Kerri L; Qi, Lihong; Sennblad, Bengt; Harris, Sarah E; Polasek, Ozren; Riess, Helene; Rivadeneira, Fernando; Rose, Lynda M; Goel, Anuj; Taylor, Kent D; Teumer, Alexander; Uitterlinden, André G; Vaidya, Dhananjay; Yao, Jie; Tang, Weihong; Levy, Daniel; Waldenberger, Melanie; Becker, Diane M; Folsom, Aaron R; Giulianini, Franco; Greinacher, Andreas; Hofman, Albert; Huang, Chiang-Ching; Kooperberg, Charles; Silveira, Angela; Starr, John M; Strauch, Konstantin; Strawbridge, Rona J; Wright, Alan F; McKnight, Barbara; Franco, Oscar H; Zakai, Neil; Mathias, Rasika A; Psaty, Bruce M; Ridker, Paul M; Tofler, Geoffrey H; Völker, Uwe; Watkins, Hugh; Fornage, Myriam; Hamsten, Anders; Deary, Ian J; Boerwinkle, Eric; Koenig, Wolfgang; Rotter, Jerome I; Hayward, Caroline; Dehghan, Abbas; Reiner, Alex P; O'Donnell, Christopher J; Smith, Nicholas L

    2015-09-10

    Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76,000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.

  17. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

    PubMed Central

    Huffman, Jennifer E.; de Vries, Paul S.; Morrison, Alanna C.; Sabater-Lleal, Maria; Kacprowski, Tim; Auer, Paul L.; Brody, Jennifer A.; Chasman, Daniel I.; Chen, Ming-Huei; Guo, Xiuqing; Lin, Li-An; Marioni, Riccardo E.; Müller-Nurasyid, Martina; Yanek, Lisa R.; Pankratz, Nathan; Grove, Megan L.; de Maat, Moniek P. M.; Cushman, Mary; Wiggins, Kerri L.; Qi, Lihong; Sennblad, Bengt; Harris, Sarah E.; Polasek, Ozren; Riess, Helene; Rivadeneira, Fernando; Rose, Lynda M.; Goel, Anuj; Taylor, Kent D.; Teumer, Alexander; Uitterlinden, André G.; Vaidya, Dhananjay; Yao, Jie; Tang, Weihong; Levy, Daniel; Waldenberger, Melanie; Becker, Diane M.; Folsom, Aaron R.; Giulianini, Franco; Greinacher, Andreas; Hofman, Albert; Huang, Chiang-Ching; Kooperberg, Charles; Silveira, Angela; Starr, John M.; Strauch, Konstantin; Strawbridge, Rona J.; Wright, Alan F.; McKnight, Barbara; Franco, Oscar H.; Zakai, Neil; Mathias, Rasika A.; Psaty, Bruce M.; Ridker, Paul M.; Tofler, Geoffrey H.; Völker, Uwe; Watkins, Hugh; Fornage, Myriam; Hamsten, Anders; Deary, Ian J.; Boerwinkle, Eric; Koenig, Wolfgang; Rotter, Jerome I.; Hayward, Caroline; Dehghan, Abbas; Reiner, Alex P.; O’Donnell, Christopher J.

    2015-01-01

    Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways. PMID:26105150

  18. Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.

    PubMed

    Tian, Yuejun; Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald; Wang, Zhiping

    2017-01-01

    Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

  19. Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis

    PubMed Central

    Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald

    2017-01-01

    Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy. PMID:28154828

  20. Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue-treatment: effect of plasma source and treatment time.

    PubMed

    Rapaille, André; Reichenberg, Stefan; Najdovski, Tome; Cellier, Nicolas; de Valensart, Nicolas; Deneys, Véronique

    2014-04-01

    The quality of fresh-frozen plasma is affected by different factors. Factor VIII is sensitive to blood component storage processes and storage as well as pathogen-reduction technologies. The level of fibrinogen in plasma is not affected by the collection processes but it is affected by preparation and pathogen-reduction technologies. The quality of plasma from whole blood and apheresis donations harvested at different times and treated with a pathogen-reduction technique, methylene blue/light, was investigated, considering, in particular, fibrinogen and factor VIII levels and recovery. The mean factor VIII level after methylene blue treatment exceeded 0.5 IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different series. The recovery of factor VIII was dependent on plasma source as opposed to treatment time. The interaction between the two factors was statistically significant. Mean levels of fibrinogen after methylene blue/light treatment exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment correlated strongly with the level before treatment. There was a negative correlation between fibrinogen level before treatment and recovery. Pearson's correlation coefficient between factor VIII recovery and fibrinogen recovery was 0.58. These results show a difference in recovery of factor VIII and fibrinogen correlated with plasma source. The recovery of both factor VIII and fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII and fibrinogen recovery did not appear to be correlated.

  1. Plasma circulating fibrinogen stability and moderate beer consumption.

    PubMed

    Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

    2003-12-01

    MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

  2. Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

    PubMed

    Ohkubo, Atsushi; Okado, Tomokazu; Miyamoto, Satoko; Hashimoto, Yurie; Komori, Shigeto; Yamamoto, Motoki; Maeda, Takuma; Itagaki, Ayako; Yamamoto, Hiroko; Seshima, Hiroshi; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

    2017-06-01

    Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  3. Fibrinogen γ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma.

    PubMed

    Omarova, Farida; Uitte de Willige, Shirley; Simioni, Paolo; Ariëns, Robert A S; Bertina, Rogier M; Rosing, Jan; Castoldi, Elisabetta

    2014-08-28

    Activated protein C (APC) resistance, often associated with the factor V (FV) Leiden mutation, is the most common risk factor for venous thrombosis. We observed increased APC resistance in carriers of fibrinogen γ gene (FGG) haplotype 2, which is associated with reduced levels of the alternatively spliced fibrinogen γ' chain. This finding prompted us to study the effects of fibrinogen and its γ' chain on APC resistance. Fibrinogen, and particularly the γA/γ' isoform, improved the response of plasma to added APC in the thrombin generation-based assay. Similarly, a synthetic peptide mimicking the C-terminus of the fibrinogen γ' chain, which binds thrombin and inhibits its activities, greatly increased the APC sensitivity of normal and FV Leiden plasma, likely due to its ability to inhibit thrombin-mediated activation of FV and FVIII. Although the fibrinogen γ' peptide also inhibited protein C activation by the thrombin/thrombomodulin complex, it still increased the sensitivity of plasma to endogenously formed APC when thrombin generation was measured in the presence of soluble thrombomodulin. We conclude that fibrinogen, and particularly fibrinogen γ', increases plasma APC sensitivity. The fibrinogen γ' peptide might form the basis for pharmacologic interventions to counteract APC resistance. © 2014 by The American Society of Hematology.

  4. Plasma fibrinogen lever and risk of coronary heart disease among Chinese population: a systematic review and meta-analysis.

    PubMed

    Song, Bin; Shu, Ying; Xu, Yuan Ning; Fu, Ping

    2015-01-01

    Coronary heart disease (CHD) remains the leading causes of death and disability for men and women in most developed countries. It may soon become the leading cause of death in developing countries. Several studies have examined the role of fibrinogen levels in the prediction of atherosclerosis and CHD events. The aim of this study was to explore the effects of plasma fibrinogen levels in Chinese patients with CHD and to examine the relationship of fibrinogen. We performed this meta-analysis of prospective studies of plasma fibrinogen level in relation to CHD risk in electronic database of Medline, EMBase, the Cochrane Library and CNKI (China National Knowledge Infrastructure). Plasma fibrinogen levels were calculated by mean difference with 95% confidence intervals (CI) in patients with CHD and related controls without CHD. The selected 23 studies included 2984 CHD cases and 2279 controls. Our results found that plasma fibrinogen levels of patients were significantly higher than control group (P<0.0001). The predicted odds ratio (OR) for a 1 g/L higher plasma fibrinogen level was 0.94 (95% CI=0.78-1.10). Furthermore, fibrinogen levels were slightly related to age-related CHD patients. The plasma fibrinogen lever was correlated with CHD in the Chinese population, and may be a risk factor and predictor of CHD. Further studies assessing any causal relevance of fibrinogen levels to disease are required.

  5. High-level expression and preparation of recombinant human fibrinogen as biopharmaceuticals

    PubMed Central

    Hirashima, Masaki; Imamura, Takayuki; Yano, Kentaro; Kawamura, Ryoichi; Meta, Akihiro; Tokieda, Yoshiyuki; Nakashima, Toshihiro

    2016-01-01

    Fibrinogen is a large and complex glycoprotein containing two sets of each of three different chains (α, β and γ). There have been no reports of high-level expression of fibrinogen at commercial levels using mammalian cultured cells such as CHO cells because of the difficulty in highly expressing a protein with such a complex structure. We achieved high-level (1.3 g/l or higher) expression of recombinant human fibrinogen using CHO DG44 cells by optimizing the expression system and culture conditions. We also succeeded in establishing a high-recovery preparation method for recombinant fibrinogen that rarely yields degraded products. To characterize the properties of the recombinant human fibrinogen, we performed SDS-PAGE; western blotting of the α, β and γ chains using specific antibodies and scanning electron microscopy observations of fibrin fibres. We also evaluated the functional equivalence between recombinant fibrinogen and plasma fibrinogen with respect to the release of fibrinopeptides initiated by thrombin and its cross-linking properties. The basic properties of recombinant fibrinogen showed no apparent differences from those of plasma fibrinogen. Here, we report the development of methods for the culture and preparation of recombinant human fibrinogen of satisfactory quality that can be scaled up to the commercial level. PMID:26475674

  6. High-level expression and preparation of recombinant human fibrinogen as biopharmaceuticals.

    PubMed

    Hirashima, Masaki; Imamura, Takayuki; Yano, Kentaro; Kawamura, Ryoichi; Meta, Akihiro; Tokieda, Yoshiyuki; Nakashima, Toshihiro

    2016-02-01

    Fibrinogen is a large and complex glycoprotein containing two sets of each of three different chains (α, β and γ). There have been no reports of high-level expression of fibrinogen at commercial levels using mammalian cultured cells such as CHO cells because of the difficulty in highly expressing a protein with such a complex structure. We achieved high-level (1.3 g/l or higher) expression of recombinant human fibrinogen using CHO DG44 cells by optimizing the expression system and culture conditions. We also succeeded in establishing a high-recovery preparation method for recombinant fibrinogen that rarely yields degraded products. To characterize the properties of the recombinant human fibrinogen, we performed SDS-PAGE; western blotting of the α, β and γ chains using specific antibodies and scanning electron microscopy observations of fibrin fibres. We also evaluated the functional equivalence between recombinant fibrinogen and plasma fibrinogen with respect to the release of fibrinopeptides initiated by thrombin and its cross-linking properties. The basic properties of recombinant fibrinogen showed no apparent differences from those of plasma fibrinogen. Here, we report the development of methods for the culture and preparation of recombinant human fibrinogen of satisfactory quality that can be scaled up to the commercial level.

  7. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.

    PubMed

    Levy, Jerrold H; Welsby, Ian; Goodnough, Lawrence T

    2014-05-01

    Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (<1.0 g/L) during major hemorrhage (normal plasma fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high-quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point-of-care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation.

  8. Utility of plasma fibrinogen in the differential diagnosis of thyrotoxicosis

    PubMed Central

    Ma, Jie; Liu, Rui; Wu, Di; Miao, Wei; Chen, Qian; Li, Yushu; Guan, Haixia

    2015-01-01

    Background: A study had reported that a low TSH level is associated with elevated plasma fibrinogen (FIB) levels. Our purpose was to investigate the role of FIB in the differential diagnosis of thyrotoxicosis. Methods: The data of 104 patients with primary thyrotoxicosis at the First Hospital of China Medical University from July 2010 to March 2011 were analyzed and divided into three groups: 45 cases of subacute thyroiditis, 50 cases of Graves’ disease, and 9 cases of toxic multinodular goiter. The patients with subacute thyroiditis were followed up before and after the treatment. FIB levels of the three groups were compared. Results: There was no significant difference in serum TSH, FT3 and FT4 between the patients with three different causes of thyrotoxicosis (P > 0.05). The proportion of hyperfibrinogenemia in patients with subacute thyroiditis was 98%. The FIB levels of patients with subacute thyroiditis were significantly higher than those with Graves’ disease and toxic multinodular goiter (P < 0.05). Levels of ESR show a similar tendency. The FIB levels returned to normal with the remission of subacute thyroiditis. Conclusions: Elevated plasma fibrinogen is a common manifestation of the active phase of subacute thyroiditis. A FIB test can be used for the differential diagnosis of thyrotoxicosis. We can anticipate the outcome of subacute thyroiditis through the dynamic changes of FIB. PMID:25785116

  9. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

    PubMed Central

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao

    2017-01-01

    Background ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. Methods A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Results Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects (p < 0.05 for all comparison). ADAMTS13 antigen decreased with increasing age, whereas the other parameters increased. Other than ADAMTS13 (p < 0.01), no gender-related variations were observed in the other parameters. Moreover, FVIII:C, Fbg, VWF:Ag, VWF:CBA, and VWF:Rcof showed significant and positive relationships with age (r = 0.421, 0.445, 0.410, 0.401, and 0.589, resp.; all p < 0.001), whereas a negative relationship was observed for ADAMTS13 antigen (r = 0.306; p = 0.006). Furthermore, FVIII:C were strongly correlated with VWF:Ag, VWF:CBA, and VWF:Rcof (r = 0.746, r = 0.746, and r = 0.576, resp.; p < 0.0001). VWF parameters were also strongly correlated with each other (r = 0.0.847 for VWF:Ag and VWF:CBA; r = 0.722 for VWF:Ag and VWF:Rcof; p < 0.0001). Conclusions ABO blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups. PMID

  10. Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury

    PubMed Central

    Kim, Cherine H.; McBride, Devin W.; Raval, Ronak; Sherchan, Prativa; Hay, Karen L.; Gren, Eric C. K.; Kelln, Wayne; Lekic, Tim; Hayes, William K.; Bull, Brian S.; Applegate, Richard; Tang, Jiping; Zhang, John H.

    2017-01-01

    Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries. PMID:28102287

  11. Comparison of plasma with whole blood prothrombin time and fibrinogen on the same instrument.

    PubMed

    Amukele, Timothy K; Ferrell, Chris; Chandler, Wayne L

    2010-04-01

    We compared plasma with whole blood (WB) international normalized ratio (INR) and fibrinogen using the same instrument and reagents. WBINRs were 50% higher than plasma INRs. After increasing the WB sample volume 40% and adjusting the International Sensitivity Index, WBINRs were similar to plasma INRs [adjusted WBINR = 0.99(plasma INR) - 0.02; r(2) = 0.98; n = 155], but the average difference in WB vs plasma INR was 4-fold higher than duplicate plasma INRs. Variation in hematocrit was a major determinant of the accuracy of the WBINR, with increased error at high INRs. The WB fibrinogen assay was highly dependent on the sample hematocrit (r(2) = 0.83), even after the sample volume was adjusted. Accurate WB fibrinogen measurements required a mathematical hematocrit correction. We conclude that WBINR and fibrinogen assays can be performed on point-of-care or automated analyzers, but sample volume must be adjusted to account for hematocrit. Accuracy is limited by variations in hematocrit with worsening accuracy for samples with high INRs or low fibrinogen levels.

  12. The acute phase reactant, fibrinogen, as a guide to plasma exchange therapy for acute Guillain-Barré syndrome.

    PubMed

    Sanjay, Rashmi; Flanagan, Janice; Sodano, Donata; Gorson, Kenneth C; Ropper, Allan H; Weinstein, Robert

    2006-07-01

    The Guillian Barré syndrome is an acute inflammatory disorder for which plasma exchange is effective treatment. Up to 10% relapse after plasma exchange suggesting that treatment sometimes finishes before disease activity has resolved. We studied whether plasma fibrinogen, an inflammatory marker, might be used to determine when to discontinue plasma exchange in patients with acute Guillain-Barré syndrome. We conducted a post-hoc analysis of apheresis database and hospital records of patients treated with plasma exchange for acute Guillain-Barré syndrome during 1999-2004. Data were analyzed from 28 patients who underwent a total of 29 courses of plasma exchange for acute Guillain-Barré syndrome. The mean (+/-SD) plasma fibrinogen concentration was 422.5 (+/-96.4) mg/dl at the time of presentation and, in 17 of the 29, it was above 400 mg/dl (reference range 200-400). Twenty of the 21 patients whose fibrinogen fell by more than 30% from baseline by the time of the final plasma exchange treatment had neurological improvement. There was improvement in only 3 of the 8 instances where fibrinogen decreased by less than 30% by the end of plasma exchange therapy. A > or =30% decrease in fibrinogen by the conclusion of plasma exchange was significantly associated with sustained neurological improvement (P = 0.0025). The plasma fibrinogen level appears to reflect disease activity in acute Guillain-Barré syndrome. A <30% fall in fibrinogen level despite plasma exchange may indicate the need to continue plasma exchange to maximize the benefit of treatment or minimize the risk of relapse. Therapeutic plasma exchange need not be extended when plasma fibrinogen remains > or =30% below its level at presentation by the time of the final planned plasma exchange procedure.

  13. Plasma Fibrinogen Correlates with Metastasis and is Associated with Prognosis in Human Nasopharyngeal Carcinoma

    PubMed Central

    He, Sha-Sha; Wang, Yan; Yang, Lin; Chen, Hai-Yang; Liang, Shao-Bo; Lu, Li-Xia; Chen, Yong

    2017-01-01

    Background: The purpose of this observational study was to evaluate the prognostic significance of the pre-treatment plasma fibrinogen level for survival outcomes in nasopharyngeal carcinoma (NPC). Methods: A total of 998 patients with NPC treated at a single centre in China were retrospectively enrolled, of whom 182 (18.2%) developed distant metastasis during follow-up. Survival analyses were performed by the Kaplan-Meier method and Cox regression modelling to measure 3-year overall survival (OS) and distant metastasis-free survival (DMFS). Results: Median OS for the entire cohort was 37.8 months. Using the cut-off value of 3.345 g/L identified in receiver operating curve analysis for fibrinogen, a high pre-treatment plasma fibrinogen level were associated with older age (P = 0.034), advanced TNM stage (P = 0.004) and development of distant metastasis (P < 0.001; Chi-square test). Multivariate Cox proportional hazard analysis demonstrated the pre-treatment plasma fibrinogen level was an independent significant prognostic factor for OS and DMFS in both the entire cohort and also among patients who developed distant metastasis during follow-up. Conclusions: This study suggests the pre-treatment plasma fibrinogen level may serve as an independent prognostic marker to predict the survival outcomes of patients with NPC, including patients with metastatic disease. PMID:28261341

  14. Daily concentrations of air pollution and plasma fibrinogen in London.

    PubMed

    Pekkanen, J; Brunner, E J; Anderson, H R; Tiittanen, P; Atkinson, R W

    2000-12-01

    The reason for the association between air pollution and risk of cardiovascular diseases is unknown. The hypothesis was examined that daily concentrations of air pollution are associated with daily concentrations of fibrinogen, a risk factor for cardiovascular disease. Data on concentrations of plasma fibrinogen for 4982 male and 2223 female office workers, collected in a cross sectional survey in London between September 1991 and May 1993, were combined with data on concentrations of air pollution during the day of blood sampling and during the 3 preceding days. After adjustment for weather and other confounding factors, an increase in the 24 hour mean NO(2) during the previous day from the 10th to the 90th percentile (61.7 microg/m(3)) was associated with a 1.5% (95% confidence interval (95% CI) 0.4% to 2.5%) higher fibrinogen concentration. The respective increase for CO (1.6 mg/m(3)) was 1.5% (95% CI 0.5%, 2.5%). These associations tended to be stronger in the warm season (April to September). Significant associations were found for black smoke and particulate matter of diameter 10 microm (PM(10)) only in the warm season. No association with fibrinogen was found for SO(2) or ozone. The short term association between air pollution, possibly from traffic, and risk of cardiovascular events may be at least partly mediated through increased concentrations of plasma fibrinogen, possibly due to an inflammatory reaction caused by air pollution.

  15. Low preoperative fibrinogen plasma concentration is associated with excessive bleeding after cardiac operations.

    PubMed

    Waldén, Katarina; Jeppsson, Anders; Nasic, Salmir; Backlund, Erika; Karlsson, Martin

    2014-04-01

    Data from small selected patient populations suggest that the preoperative plasma concentration of fibrinogen influences postoperative blood loss and red blood cell transfusion after cardiac operations, but there are also conflicting reports. We assessed the importance of preoperative fibrinogen concentration for excessive bleeding and red cell blood transfusion in a large cohort of mixed cardiac surgical patients. We included 1,954 cardiac surgical patients in a prospective observational study. The fibrinogen plasma concentration was measured on the day before the operation. Blood loss (mediastinal drain volume) during the first 12 postoperative hours and red blood cell transfusion during the hospital stay were registered and related to fibrinogen concentration with logistic regression models. Excessive bleeding was defined as postoperative blood loss exceeding 1,000 mL/12 hours. The preoperative fibrinogen concentration was inversely proportional to the prevalence of excessive bleeding in univariate testing (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.64 to 0.89 per g/L; p=0.001) and also in a multiple model adjusted for age, sex, body mass index, renal function, acuteness of the operation, cardiopulmonary bypass time, clopidogrel use less than 5 days before the operation, and type of operation (OR for fibrinogen, 0.82; 95% CI, 0.69 to 0.97; p=0.024). In contrast, the prevalence of red cell blood transfusion increased with increasing fibrinogen levels in univariate testing (OR, 1.36; 95% CI, 1.24 to 1.49; p<0.001) but not in a multiple model (OR, 1.10; 95% CI, 0.89 to 1.28; p=0.49). Preoperative plasma concentration of fibrinogen is independently associated with excessive bleeding after cardiac operations but not with red blood cell transfusion. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Fibrinogen blood test

    MedlinePlus

    Serum fibrinogen; Plasma fibrinogen; Factor I; Hypofibrinogenemia test ... Chernecky CC, Berger BJ. Fibrinogen (factor I) - plasma. In: ... Louis, MO: Elsevier Saunders; 2013:525. Schmaier AH. Laboratory ...

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

    PubMed

    Berger, Martin D; Heini, Alexander D; Seipel, Katja; Mueller, Beatrice; Angelillo-Scherrer, Anne; Pabst, Thomas

    2016-06-15

    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.

  18. Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

    PubMed Central

    2011-01-01

    Introduction Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. Methods Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. Results Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital

  19. Lifecourse predictors of adult fibrinogen levels: the Newcastle Thousand Families Study.

    PubMed

    Pearce, Mark S; Ahmed, Ahmed; Tennant, Peter W G; Parker, Louise; Unwin, Nigel C

    2012-03-08

    Research investigating early life effects on fibrinogen levels in adult life has produced conflicting results. The aim of this study was to examine and quantify the direct and indirect associations between fetal, infancy and adult risk factors and fibrinogen levels, at age 49-51 years, using data from the Newcastle Thousand Families Study. Detailed information was collected prospectively during childhood, including birth weight, duration of being breast fed and socio-economic conditions. At age 49-51 years, 574 study members returned self-completion questionnaires and 412 attended for clinical examination, including the measurement of plasma fibrinogen concentrations in 173 men and 221 women. These data were analysed using linear regression and path analyses. Poorer quality housing conditions at birth (p=0.001), longer duration of being breast fed (p=0.025), lower current body fat percentage (p<0.001), not being a current smoker (p<0.001) and moderate current alcohol consumption (p=0.002) were significant independent predictors of lower plasma fibrinogen concentration at age 49-51 years. No association was observed between plasma fibrinogen concentration and standardised birth weight or with time since stopping smoking among former smokers. Concentration of plasma fibrinogen in adulthood is influenced by a range of factors from different stages of life. Although birth weight was not a predictor, there were significant associations with housing conditions in early life and duration of being breast fed. Regardless, the strongest predictors were smoking and contemporary percent body fat. Therefore, modification of these factors would be the most likely way to reduce concentrations of plasma fibrinogen in adulthood. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Fibrinogen measurements in plasma and whole blood: a performance evaluation study of the dry-hematology system.

    PubMed

    Ogawa, Satoru; Tanaka, Kenichi A; Nakajima, Yasufumi; Nakayama, Yoshinobu; Takeshita, Jun; Arai, Masatoshi; Mizobe, Toshiki

    2015-01-01

    An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO®) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91-0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from

  1. Fibrinogen salvage during DF Thermo using Evaflux-5A plasma fractionators.

    PubMed

    Nakashima, Momoko; Yasui, Masahide; Ihara, Akira

    2012-10-01

    DF Thermo, a modified form of double-filtration plasmapheresis (DFPP), has been used for the treatment of various indications such as arteriosclerosis obliterans (ASO). In case of ASO, fibrinogen is a substance to be removed by DFPP. On the other hand, plasmapheresis for chronic viral hepatitis C became an insurance covered treatment in Japan in April 2008. Since then DFPP has also become a treatment of chronic viral hepatitis C as an adjunctive therapy for the purpose of improving the effect of medication. Therefore, there has been a growing concern in recent years about patients' low fibrinogen levels due to DFPP treatment. With the aim of improving fibrinogen retention by DF Thermo, we examined by in vitro trial, the effects when recirculating the filtrate and elevating its temperature. The trial was conducted using bovine plasma, run through experimental circuits with the same configuration as the clinical setting of the One-Way method and DF Thermo method. The DF Thermo circuit contained a thermostat, on which the temperature was set to 40°C. Two One-Way method circuits were prepared with different temperature settings, i.e., 20°C and 40°C. With these three different conditions, variance of the fibrinogen retention under different temperatures and the implementation of recirculation were compared. Results show that the DF Thermo circuit tends to have enhanced the fibrinogen retention compared to the One-Way method 20°C and 40°C. The explanation is likely as follows: viscosity of plasma reduces when warmed, which in turn helps maintain the permeability of membrane, and the recirculation of the plasma helps prevent membrane fouling, thus more fibrinogen is retained in the DF Thermo method.

  2. Fibrinogen adsorption and host tissue responses to plasma functionalized surfaces.

    PubMed

    Tang, L; Wu, Y; Timmons, R B

    1998-10-01

    The physical and chemical characteristics of material surfaces are thought to play important roles in biomaterial-mediated tissue responses. To understand the importance of discrete biomaterial chemical characteristics in modifying host tissue responses, we constructed surfaces bearing different functional groups using radio frequency glow discharge plasma polymerization. Surfaces evaluated included those having high concentrations of -OH, -NH2, -CF3, and siloxyl groups. These surfaces and polyethylene terephthalate controls were used to assess the importance of particular physicochemical characteristics in surface:protein:cell interactions both in vitro and in vivo. The results obtained show that surface functionalities do significantly affect both the adsorption and "denaturation" of adsorbed fibrinogen (which is an important mediator of inflammatory responses to biomaterial implants). In addition, these surfaces provoke different degrees of acute inflammatory responses. Interestingly, the amounts of "denatured" fibrinogen that spontaneously accumulate on the individual surfaces correlate closely with the extent of biomaterial-mediated inflammation. These results suggest that surfaces that tend to "irreversibly" bind fibrinogen prompt greater acute inflammatory responses. Unexpectedly, all test surfaces except those bearing a siloxyl group engender relatively similar biomaterial-mediated fibrotic responses. Thus surface functionalities alone may not be sufficient to affect subsequent fibrotic responses.

  3. Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

    PubMed

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Mizugaki, Asumi; Katabami, Kenichi; Maekawa, Kunihiko; Miyamoto, Daisuke; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi

    2015-04-01

    Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p < 0.001). Error grid analysis showed that 88% of the values were clinically acceptable, and 12% were in a range with possible effects on clinical decision-making; none were in a clinically dangerous range without appropriate treatment. Using a fibrinogen cutoff value of 1.5 g/L for standard-Fbg, the area under the receiver operating characteristic curve of whole blood-Fbg was 0.980 (95% confidence interval 0.951-1.000, p < 0.001). The whole blood coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern.

  4. Effect of resveratrol on hemostatic properties of human fibrinogen and plasma during model of hyperhomocysteinemia.

    PubMed

    Malinowska, Joanna; Olas, Beata

    2010-11-01

    Resveratrol (3,4', 5 - trihydroxystilben), a phenolic antioxidant synthesized in grapes and vegetables and presents in wine, has been supposed to be beneficial for the prevention of cardiovascular events. In this study the influence of resveratrol on the clot formation (using human plasma and purified fibrinogen) and the fibrin lysis during model of hyperhomocysteinemia was investigated. We induced this process using a reduced form of Hcys (at final dose of 0.1mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 0.5μM). The aim of our study in vitro was to investigate the modifications of human plasma total proteins after incubation with Hcys, HTL and resveratrol. We observed that HTL, like its precursor, Hcys stimulated polymerization of fibrinogen. Our present results also demonstrated that Hcys (0.1mM) and HLT at lower doses than Hcys (0.5μM) reduced the fibrin lysis in human plasma. Moreover, Hcys and HTL change the level of thiol and amino groups in plasma total proteins. Our results indicate that resveratrol reduced the toxicity action of Hcys and HTL on hemostatic properties of fibrinogen or plasma, suggesting its possible protector role in hyperhomocysteinemia - induced cardiovascular diseases.

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

    PubMed

    Naji, Duraid Hamid; Tan, Chengcheng; Han, Fabin; Zhao, Yuanyuan; Wang, Junhan; Wang, Dan; Fa, Jingjing; Li, Sisi; Chen, Shanshan; Chen, Qiuyun; Xu, Chengqi; Wang, Qing K

    2017-09-11

    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.

  6. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded carrageenan].

    PubMed

    Cong, Haixia; Yin, Liang; Fang, Bo; Du, Longbing; Zhao, Hui; Chen, Jingling; You, Chao

    2010-08-01

    The selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded carrageenan was studied by the present authors. Degraded carrageenan was prepared by acid with carrageenan as the main material. The effects of acid conditions on the molecular weight were investigated, and the proper reaction conditions were ascertained. The results of infrared spectrometry indicated that the degraded carrageenan is a heparin-like polysaccharide. Then the selective removal of LDL/Fibrinogen by degraded carrageenan was studied. When molecular weight was about 10,000, pH was 5.10 and the concentration of degraded carrageenan was 800 mg/L, the average reduction percentages were 60.0% for total cholesterol(TC), 79.4% for LDL and very low-density lipoprotein (VLDL), and 93.8% for fibrinogen. There were no significant changes with relation to the level of high-density lipoprotein (HDL) and total protein (TP). So, degraded carrageenan was shown to be of good selectivity on plasma LDL/Fibrinogen apheresis.

  7. Predictive Role of Intraoperative Plasma Fibrinogen for Postoperative Portal Venous Flow in Living Donor Liver Transplantation.

    PubMed

    Chae, Min Suk; Park, Chul Soo; Oh, Su A; Hong, Sang Hyun

    2017-02-14

    BACKGROUND Previous studies have reported poor graft regeneration after living donor liver transplantation (LDLT) due to inappropriate portal venous flow (PVF). In this study, we investigated the perioperative factors affecting postoperative PVF after LDLT. MATERIAL AND METHODS The perioperative data of 366 LDLT patients were retrospectively reviewed. The average PVF on postoperative days 1, 3, and 5 was measured and dichotomized at a cut-off value for patient survival of 1,477 mL/min. Perioperative variables, including coagulation profiles, were compared between high and low postoperative PVF groups. The factors potentially significant (p<0.1) for a low postoperative PVF were evaluated in a univariate analysis, followed by the development of a predictive model for a low postoperative PVF. RESULTS A low post-LDLT PVF was determined in 113 patients (30.9%). The univariate analysis identified systemic hypertension, LDLT duration, average mean blood pressure, and insulin administration as the significantly related factors. Other significant factors were a plasma fibrinogen, at the anhepatic phase and 1 h after graft reperfusion, as well as the platelet count at the anhepatic phase. After multivariate adjustment, plasma fibrinogen 1 h after graft reperfusion against a recipient background of systemic hypertension was independently associated with a low mean postoperative PVF. CONCLUSIONS A low mean PVF during the early post-LDLT period was independently related to the plasma fibrinogen level 1 h after graft reperfusion, and to a history of systemic hypertension. Thus, the practice of aggressive supplementation of plasma fibrinogen during the immediate post-reperfusion period merits serious consideration.

  8. Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study.

    PubMed

    Pankow, J S; Folsom, A R; Province, M A; Rao, D C; Williams, R R; Eckfeldt, J; Sellers, T A

    1998-10-01

    Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations are risk factors for coronary heart disease. We investigated environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertained families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether mendelian inheritance of a major gene could best explain the familial distributions of these 2 hemostatic factors. Age- and gender-adjusted familial correlations for PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to 0.21); the spouse correlation was positive but not statistically significant (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major gene associated with higher PAI-1 concentrations in 65% of individuals from these families. Demographic, anthropometric, lifestyle, and metabolic characteristics together explained 37% to 47% of the variation in PAI-1 antigen levels, and the inferred major gene explained an additional 17% of the variance. Positive and statistically significant age- and gender-adjusted familial correlations in first-degree relatives indicated a possible heritable component influencing plasma fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation analysis did not provide statistical evidence of a major gene controlling fibrinogen level. These family data suggest that there are modest familial and genetic effects on the concentration of PAI-1.

  9. 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.

    PubMed

    Lan, Mei; Chen, Chunyan; Huang, Ying; Mao, Minjie; Han, Fei; Liao, Junfang; Deng, Meiling; Duan, Zhijun; Zheng, Lie; Wu, Shaoxiong; Lu, Taixiang; Jian, Yutao

    2016-07-19

    Effective 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). The 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. High pretreatment FIB level shows superior prognostic value than EBV-DNA load for stage IVA/B NPC patients in the era of IMRT. A 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.

  10. 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

    PubMed Central

    Huang, Ying; Mao, Minjie; Han, Fei; Liao, Junfang; Deng, Meiling; Duan, Zhijun; Zheng, Lie; Wu, Shaoxiong; Lu, Taixiang; Jian, Yutao

    2016-01-01

    Purpose Effective 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). Results The 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. Conclusion High pretreatment FIB level shows superior prognostic value than EBV-DNA load for stage IVA/B NPC patients in the era of IMRT. Materials and Methods A 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. PMID:27323828

  11. Blood fibrinogen levels discriminate low- and high-risk intraductal papillary mucinous neoplasms (IPMNs).

    PubMed

    Nentwich, M F; Menzel, K; Reeh, M; Uzunoglu, F G; Ghadban, T; Bachmann, K; Schrader, J; Bockhorn, M; Izbicki, J R; Perez, D

    2017-04-01

    The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection. Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured. A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant. Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  12. Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: a prospective observational study.

    PubMed

    Pillai, Ravi C; Fraser, John F; Ziegenfuss, Marc; Bhaskar, Balu

    2014-03-01

    Fibrinogen, the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In this prospective cohort study, we measured patient's fibrinogen levels and common coagulation parameters before and after cardiopulmonary bypass (CPB) and examined their relationships with postoperative blood loss. Patients undergoing cardiac surgery with CPB who did not have pre-existing coagulopathy were eligible. Standard blood and coagulation testing were performed before and after CPB. The association of these variables with postoperative blood loss (estimated blood loss from CPB) was assessed with Spearman's ranked correlation and multivariable linear regression models. Two hundred and fifty patients were enrolled in the study. The median blood loss was 780 mL (range 320-2340 mL). Variables independently associated with increasing blood loss were lower post-CPB platelet counts (p<0.001), lower postoperative fibrinogen levels (p<0.001), and larger percent decrease in fibrinogen levels (p<0.05). There was no correlation between preoperative fibrinogen levels and preoperative coagulation tests with postoperative bleeding. The only significant independent predictors of transfusion in a logistic regression model were postoperative fibrinogen concentration. Postoperative fibrinogen, the larger percent decrease in fibrinogen, and postoperative platelet levels are markers of bleeding and blood transfusion requirements after CPB than preoperative standard screening tests. Postoperative fibrinogen had the best predictive value of all tests of postoperative blood loss.

  13. Correlation of a clot-weight and radial immunodiffusion method for estimation of plasma fibrinogen concentration.

    PubMed

    Reid, H L; Onwuameze, I C

    1984-03-01

    A clot-weight and radial immunodiffusion method for estimating fibrinogen concentration were compared using plasma from 58 pregnant women and diabetic patients. The two methods gave a correlation coefficient, r = 0.53 (p less than 0.005). There was no significant variation between the mean fibrinogen concentrations as determined by both methods. The coefficient of variation for the clot-weight and immunodiffusion methods were 1.54% and 2.9%, respectively. It is concluded that the clot-weight method is more readily applicable than the radial immunodiffusion method to fibrinogen measurements, especially in patients when rapid results are required.

  14. The effect of assembly and transit stressors on plasma fibrinogen concentration of beef calves.

    PubMed Central

    Phillips, W A

    1984-01-01

    Plasma fibrinogen concentration was measured in beef calves at various points within the system presently used to assemble, market and transport calves from one production point to another in order to determine the effect of the stresses encountered. A short haul of 160 km immediately after weaning did not significantly elevate fibrinogen concentration above the pretransit values. Yearling steers transported 400 km and confined in unfamiliar surroundings for 15 h did have an elevated (P less than 0.01) concentration of fibrinogen, but this increase was not significantly different from that of steers which were confined but not transported, thus confinement may be a significant portion of the stress associated with transit. The change in plasma fibrinogen concentration during assembly and transit was dependent upon the farm from which the calves originated. The magnitude of the change in fibrinogen concentration as a result of assembly and transit varied between the years studied. In one year pretransit assembly for ten days resulted in a higher fibrinogen concentration before and after transit than assembly for four days, but no difference was noted between the two groups in the second year. Bovine plasma fibrinogen concentration does increase in response to the stresses associated with assembly and transit. The stress of fasting and housing in unfamiliar surroundings also increase bovine plasma fibrinogen concentration and are present in the assembly and transit system. These two stresses may account for a majority of the stress associated with marketing and transit. The response of beef calves to the marketing and transit system varied between years. PMID:6713254

  15. Adsorption Studies with AFM of Human Plasma Fibrinogen on Silicon Surfaces

    NASA Astrophysics Data System (ADS)

    Gause, Sheena; Kong, Wendy; Rowe

    2007-11-01

    Fibrinogen (FGN) plays an important role in the clotting of blood. Human plasma fibrinogen (HPF) is a protein that readily adsorbs on biomaterial surfaces. The purpose of this experiment was to use the Atomic Force Microscope to study the adsorption of HPF molecules or FGN onto several silicon surfaces with different orientations and resistivities. The size of the FGN molecules found to be somewhat different of Si(111), (100) and (110) were compared to the size of the FGN molecules in solution (45 nm in length, the end dynodes measures to be 6.5 nm in diameter, and the middle dynode measures to be 5 nm in diameter. For this study, the CPR (Thermo-microscope) Atomic Force Microscope (AFM) was used to observe the amount of fibrinogen molecules adsorbed by Si (111) with a resistance of .0281-.0261 φ cm, Si (111) with a resistance of 1 φ cm, Si (100), and Si (110) surfaces. In finding any single fibrinogen molecules, the appropriate image scans and measurements were taken. After collection and analysis of the data, it was found from AFM that the fibrinogen molecules found on Si (110) mostly resembled fibrinogen molecules found in solution. The other images showed that the fibrinogen molecules adsorbed on Silicon substrates is significantly greater (˜10-20 %) than those in solution.

  16. Characterization of fibrinogen glycosylation and its importance for serum/plasma N-glycome analysis.

    PubMed

    Adamczyk, Barbara; Struwe, Weston B; Ercan, Altan; Nigrovic, Peter A; Rudd, Pauline M

    2013-01-04

    The majority of proteins present in human serum/plasma are glycoproteins, validating this fluid as an ideal starting material for N-glycan analysis and discovery of potential biomarkers. The glycoprotein content for both serum and plasma is very similar, except for proteins removed in the coagulation process, including fibrinogen. Our aim was to characterize fibrinogen glycosylation in order to determine its contribution to differences between serum and plasma N-glycomes. N-Glycans from human fibrinogen were released, labeled, and analyzed by HILIC-HPLC and MS. Structural characterization of fibrinogen subunits revealed that the α chain was not N-glycosylated, whereas β and γ contained identical oligosaccharide structures, mainly biantennary digalactosylated monosialylated structures (A2G2S1) and biantennary digalactosylated disialylated structures (A2G2S2). Blood was collected from five healthy volunteers into four testing tubes: silicone-coated glass for serum and EDTA, Na-heparin, and Li-heparin glass tubes for plasma. N-Glycans were analyzed using the high-throughput HILIC-HPLC method. N-Glycan profiles from serum and plasma samples differed largely in glycans identified in fibrinogen, suggesting that this glycoprotein represents a major factor distinguishing these body fluids. This result emphasizes the important of consistent body fluid collection practices in biomarker discovery studies.

  17. Fibrinogen plasma concentration is an independent marker of haemodynamic impairment in chronic thromboembolic pulmonary hypertension

    PubMed Central

    Hennigs, Jan K.; Baumann, Hans Jörg; Lüneburg, Nicole; Quast, Gesine; Harbaum, Lars; Heyckendorf, Jan; Sydow, Karsten; Schulte-Hubbert, Bernhard; Halank, Michael; Klose, Hans

    2014-01-01

    Fibrinogen has a crucial role in both inflammation and coagulation, two processes pivotal for the pathogenesis of pulmonary hypertension. We therefore aimed to investigate whether fibrinogen plasma concentrations a) are elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and b) may serve as a novel biomarker for haemodynamic impairment. In a dual-centre, retrospective analysis including 112 patients with PAH (n = 52), CTEPH (n = 49) and a control cohort of patients with suspected PAH ruled out by right heart catheterisation (n = 11), we found fibrinogen plasma concentrations to be increased in patients with PAH (4.1 ± 1.4 g/l) and CTEPH (4.3 ± 1.2 g/l) compared to control patients (3.4 ± 0.5 g/l, p = 0.0035 and p = 0.0004, respectively). In CTEPH patients but not in PAH patients fibrinogen was associated with haemodynamics (p < 0.036) and functional parameters (p < 0.041). Furthermore, fibrinogen was linked to disease severity (WHO functional class, p = 0.017) and independently predicted haemodynamic impairment specifically in CTEPH (p < 0.016). Therefore, fibrinogen seems to represent an important factor in CTEPH pathophysiology and may have the potential to guide clinical diagnosis and therapy. PMID:24770447

  18. Fibrinogen and ceruloplasmin in plasma and milk from dairy cows with subclinical and clinical mastitis.

    PubMed

    Tabrizi, A Davasaz; Batavani, R A; Rezaei, S Asri; Ahmadi, M

    2008-02-15

    The potential using of Acute Phase Proteins (APPs) in the assessment of mammary gland health was studied by examining the levels of Fibrinogen (Fb) and Ceruloplasmin (Cp) in plasma and milk from dairy cows with different grades of mastitis. Plasma samples were taken from jugular vein and milk samples were collected from quarters of cows with subclinical and clinical mastitis, as well as healthy controls. California Mastitis Test (CMT) were performed on each udder quarter of cows for detection of CMT2+ and CMT3+ quarters. CMT (0) and culture negative cases were considered healthy cows. Clinical mastitis, was graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s). The concentrations of Fb in the plasma of the cows with subclinical and clinical mastitis were higher than in the plasma of the healthy cows (p<0.01). There was no significant difference in plasma concentration of Cp between healthy and subclinical groups (p>0.05), but differences between clinical and healthy groups were significant (p<0.05). The concentrations of Fb and Cp in the milk of the cows with subclinical and clinical mastitis were higher than in the milk of the healthy cows (p<0.01). The results indicated that measurement of Fb in plasma and milk and Cp only in milk might be suitable for early diagnosis of mastitis in dairy cows.

  19. Platelet fibrinogen

    PubMed Central

    Castaldi, P. A.; Caen, J.

    1965-01-01

    Platelet fibrinogen has been studied in normal, thrombasthenic, and hypofibrinogenaemic subjects. It has been differentiated into adsorbed (plasma) and extractable (intraplatelet) fractions. Isotopic studies suggest that exchange does not occur between intraplatelet and plasma fibrinogen and it appears possible that the intra-platelet fraction may be derived from the megakaryocyte. Six of nine thrombasthenic patients were found to have a severe deficiency of both adsorbed and extractable fibrinogen. Since the remaining three had near-normal platelet fibrinogen and all nine failed to aggregate it is improbable that the failure to adsorb fibrinogen is responsible for the defect in aggregation. Magnesium partially corrects adhesion to fibrin and clot retraction by these platelets, but has not been found to influence their fibrinogen adsorption. It is considered that the basic platelet surface defect, of varying severity, is responsible for the abnormalities of adsorption, aggregation, and adhesion in thrombasthenia. In the case of congenital hypofibrinogenaemia, fibrinogen transfusion corrects the long bleeding time, platelet-adsorbed fibrinogen, and the ability of platelets to spread on glass. It is possible that fibrinogen influences the surface properties of human platelets, although the final mechanism is not determined. Images PMID:5835438

  20. Randomised clinical trial of an intensive intervention in the primary care setting of patients with high plasma fibrinogen in the primary prevention of cardiovascular disease

    PubMed Central

    2012-01-01

    Background We have studied the possible effects of an intensive lifestyle change program on plasma fibrinogen levels, in patients with no cardiovascular disease, with elevated levels of fibrinogen, normal cholesterol levels, and a moderate estimated risk of coronary heart disease (CHD) and we have also analysed whether the effect on fibrinogen is independent of the effect on lipids. Results This clinical trial was controlled, unblinded and randomized, with parallel groups, done in 13 Basic Health Areas (BHA) in l'Hospitalet de Llobregat (Barcelona) and Barcelona city. The study included 436 patients, aged between 35 and 75 years, with no cardiovascular disease, elevated levels of fibrinogen (> 300 mg/dl), cholesterol < 250 mg/dl, 218 of whom received a more intensive intervention consisting of advice on lifestyle and treatment. The follow-up frequency of the intervention group was every 2 months. The other 218 patients followed their standard care in the BHAs. Fibrinogen, plasma cholesterol and other clinical biochemistry parameters were assessed. The evaluation of the baseline characteristics of the patients showed that both groups were homogenous. Obesity and hypertension were the most prevalent risk factors. After 24 months of the study, statistically significant changes were seen between the adjusted means of the two groups, for the following parameters: fibrinogen, plasma cholesterol, systolic and diastolic blood pressure and body mass index. Conclusion Intensive intervention to achieve lifestyle changes has shown to be effective in reducing some of the estimated CHD factors. However, the effect of intensive intervention on plasma fibrinogen levels did not correlate with the variations in cholesterol. Trial Registration ClinicalTrials.gov: NCT01089530 PMID:22381072

  1. Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets.

    PubMed Central

    Harrison, P; Wilbourn, B; Debili, N; Vainchenker, W; Breton-Gorius, J; Lawrie, A S; Masse, J M; Savidge, G F; Cramer, E M

    1989-01-01

    The origin of platelet alpha-granule fibrinogen (Fg), whether from endogeneous synthesis or exogeneous derivation, remains unknown. Although Fg biosynthesis by megakaryocytes (MK) has been suggested, recent studies have demonstrated that certain alpha-granular proteins originate primarily from plasma. To study the origin of alpha-granule Fg, platelet-associated Fg was measured by ELISA and Western blotting, and localized by immunofluorescence and immunoelectron microscopy in a patient with symptomatic congenital afibrinogenemia before and after replacement therapy with cryoprecipitate. alpha-Granule Fg was detected in the majority of platelets as early as 24 h postinfusion, suggesting that direct platelet uptake was occurring. Platelet Fg reached a maximum value of 42.5% of normal values at 3 d postinfusion and was localized in the alpha-granules, while plasma levels followed a typical half-life profile. Significant alpha-granule Fg was still detectable at 13 d postinfusion, with plasma Fg virtually absent. Studies on cultured CFU-MKs from the patient also confirmed that MKs can incorporate exogeneous Fg into alpha-granules. These results indicate that platelet alpha-granule Fg can be derived from the circulating plasma pool and that Fg uptake can occur in both platelets and MKs. Images PMID:2677051

  2. In vitro sealing of iatrogenic fetal membrane defects by a collagen plug imbued with fibrinogen and plasma.

    PubMed

    Engels, A C; Hoylaerts, M F; Endo, M; Loyen, S; Verbist, G; Manodoro, S; DeKoninck, P; Richter, J; Deprest, J A

    2013-02-01

    We aimed to demonstrate local thrombin generation by fetal membranes, as well as its ability to generate fibrin from fibrinogen concentrate. Furthermore, we aimed to investigate the efficacy of collagen plugs, soaked with plasma and fibrinogen, to seal iatrogenic fetal membrane defects. Thrombin generation by homogenized fetal membranes was measured by calibrated automated thrombography. To identify the coagulation caused by an iatrogenic membrane defect, we analyzed fibrin formation by optical densitometry, upon various concentrations of fibrinogen. The ability of a collagen plug soaked with fibrinogen and plasma was tested in an ex vivo model for its ability to seal an iatrogenic fetal membrane defect. Fetal membrane homogenates potently induced thrombin generation in amniotic fluid and diluted plasma. Upon the addition of fibrinogen concentrate, potent fibrin formation was triggered. Measured by densiometry, fibrin formation was optimal at 1250 µg/mL fibrinogen in combination with 4% plasma. A collagen plug soaked with fibrinogen and plasma sealed an iatrogenic membrane defect about 35% better than collagen plugs without these additives (P = 0.037). These in vitro experiments suggest that the addition of fibrinogen and plasma may enhance the sealing efficacy of collagen plugs in closing iatrogenic fetal membrane defects. © 2013 John Wiley & Sons, Ltd.

  3. Endothelial dysfunction correlates with plasma fibrinogen and HDL cholesterol in type 2 diabetic patients with coronary artery disease.

    PubMed

    Bosevski, M; Borozanov, V; Peovska, I; Georgievska-Ismail, L

    2007-01-01

    Assessment of endothelial dysfunction (ED) in type 2 diabetic patients with coronary artery disease (CAD) and estimation of correlation of ED with metabolic parameters: low HDL, hypertriglyceridemia, obesity, systolic blood pressure and with inflammatory-hemostatic parameters: CRP and fibrinogen. 42 patients (age 60.0 +/- 8.5 years) with diagnosed type 2 diabetes and CAD were randomly included in a cross sectional study. B-mode ultrasound system with a linear transducer 7.5 MHz was used for evaluation of flow mediated vasodilation in brachial artery (FMV). FMV was presented as the percentage increase in brachial artery diameter, within 30 s after limb ischemia, previously provoked by cuff inflation. Percentage value up to 10% was defined as ED. Bivariate linear correlation model presented significant correlation between plasma fibrinogen and FMV percentage, with r -0.47, p < 0.01. Presence of ED correlates linearly with plasma level of HDL < 1.03 mmol/L (r -0.35, p < 0.03). Multivariate analysis using Backward Wald model presented fibrinogen (OR 3.14, 95% CI 0.87-11.28) and low HDL (OR 5.16, 95% CI 0.53-60.39) as factors correlated with the presence of endothelial dysfunction. These results presented plasma fibrinogen level and low HDL < 1.03 mmol/L as factors, independently correlated to the presence of endothelial dysfunction in type 2 diabetic patients with coronary artery disease (Tab. 8, Fig. 1, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

  4. Structural changes in plasma circulating fibrinogen after moderate beer consumption as determined by electrophoresis and spectroscopy.

    PubMed

    Gorinstein, Shela; Caspi, Abraham; Goshev, Ivan; Aksu, Sevil; Salnikow, Johann; Scheler, Christian; Delgado-Licon, Efren; Rosen, Anda; Weisz, Moshe; Libman, Imanuel; Trakhtenberg, Simon

    2003-01-29

    The effects of short-term moderate beer consumption (MBC) on plasma circulating fibrinogen (PCF) in patients suffering from coronary atherosclerosis were investigated by use of 2-dimensional electrophoresis (2-DE), circular dichroism (CD), and Fourier transform infrared spectroscopy (FT-IR). Forty-eight volunteers after coronary bypass surgery were divided into experimental (EG) and control (CG) groups, each of 24. Patients of the EG group consumed 330 mL of beer/day (about 20 g of alcohol) for 30 consecutive days, and CG volunteers drank mineral water instead of beer. Blood samples were collected before and after the experiment. In 21 out of 24 patients after beer consumption the plasma circulating fibrinogen was compromised: changes in its secondary structure were found. These changes were expressed in relatively low electrophoretic mobility and charge heterogeneity, decrease in alpha-helix and increase in beta-sheet, and in slight shift of amide I and II bands. Our findings indicate that one of the positive benefits of moderate beer consumption is to diminish the production of fibrinogen and its stability, which reduces the potential risk exerted by this protein. Thus, in most of beer-consuming patients some qualitative structural changes in plasma circulating fibrinogen were detected.

  5. Effects of ophthalmic disease on concentrations of plasma fibrinogen and serum amyloid A in the horse.

    PubMed

    Labelle, A L; Hamor, R E; Macneill, A L; Lascola, K M; Breaux, C B; Tolar, E L

    2011-07-01

    There is little scientific information available about the ability of ocular disease to cause a systemic inflammatory response. Horses are frequently affected with ocular disease and ensuring their systemic health prior to performing vision saving surgery under anaesthesia is essential for the successful treatment of ophthalmic disease. Ocular disease will cause elevations in the concentration of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. Whole blood and serum samples were obtained from 38 mature horses with ulcerative keratitis or uveitis and no evidence of systemic disease, 9 mature horses with no evidence of ocular or systemic disease (negative controls) and 10 mature horses with systemic inflammatory disease and no evidence of ocular disease (positive controls). Blood samples were assayed for concentrations of the acute phase proteins fibrinogen and serum amyloid A. Fibrinogen and serum amyloid A were significantly different in the positive control group compared to the negative control, corneal disease and uveitis groups (P<0.126). There was no significant difference between the negative control, corneal disease and uveitis groups (P<0.001). Ulcerative keratitis and anterior uveitis are not associated with elevated concentrations of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. When the clinician is presented with a patient with ocular disease and elevated plasma fibrinogen or serum amyloid A concentrations, a nonocular inflammatory focus should be suspected. © 2011 EVJ Ltd.

  6. Vitamin K-dependent coagulation factors and fibrinogen levels in FFP remain stable upon repeated freezing and thawing.

    PubMed

    Ben-Tal, Ofira; Zwang, Ety; Eichel, Roza; Badalbev, Tanya; Hareuveni, Mara

    2003-07-01

    FFP is considered adequate for transfusion up to 24 hours after thawing and is currently used most often to replace deficient clotting factors, such as in warfarin overdose. We set to examine the levels of vitamin K-dependent factors (i.e., prothrombin, FVII, F IX, FX), as well as fibrinogen, upon twice freezing and thawing of FFP. If factor levels in refrozen FFP remain within normal limits, this component can possibly be transfused, thus avoiding wastage of precious blood components. Twenty units of FFP, five units of each blood group A, B, AB, and O, were thawed, and aliquots were taken for measurement of coagulation factors. The plasma units were then kept for 24 hours at 4 degrees C, at which point a second aliquot was taken, The remaining FFP units were refrozen and kept at -80 degrees C for 1 week. The above procedure was then repeated. Coagulation-factor activity and fibrinogen level were measured by the coagulation analyzer. The mean levels of prothrombin, FVII, F IX, FX, and fibrinogen of each blood group (A, B, AB, and O) were calculated for each of four time points and found not statistically different (p > 0.05). Therefore, the rest of the analysis was done for all 20 FFP units as one group. The mean +/- SD levels of each coagulation factor at each time point demonstrated that all levels were within normal limits of all factors measured and that for none of the factors was there a significant decay of activity. The levels of prothrombin, FVII, F IX, FX, and fibrinogen remain stable and adequate for transfusion in twice-thawed-and-refrozen FFP. This component can be safely used for transfusion as a source of vitamin K-dependent clotting factors and fibrinogen.

  7. Carotid intima-media thickness and plasma fibrinogen among subjects with metabolic syndrome: Isfahan cohort study, Iran

    PubMed Central

    Bayanfar, Zahra; Sadeghi, Masoumeh; Heidari, Ramin; Gharipour, Mojgan; Talaie, Mohammad; Sedaghat, Akram

    2014-01-01

    BACKGROUND The role of plasma fibrinogen, a key regulator of inflammation processes and increased carotid intima-media thickness (cIMT) to predict metabolic syndrome (MetS) is currently under investigation. We assessed differences in the indicators of cIMT and also plasma fibrinogen level between MetS and non-MetS subjects. We also assessed the role of these two parameters for independently relationship with MetS state. METHODS The subjects in this cross-sectional survey were population-based samples of 93 men and women aged ≥ 35 years and over who were selected from the Isfahan cohort study, Isfahan, Iran. Fibrinogen was measured by the clotting assay of Clauss. Ultrasound studies of the carotid artery were performed to measure cIMT. MetS defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. RESULTS The mean level of plasma fibrinogen was not different in the two groups with and without MetS (240.10 ± 27.80 vs. 242.56 ± 35.82, P = 0.714), but the mean of cIMT was considerably higher in MetS group than in non-MetS group (0.85 ± 0.06 mm vs. 0.66 ± 0.09 mm, P < 0.001). Using a multivariable logistic regression model, high cIMT could effectively predict MetS state with the presence of different components of MetS (odds ratio = 17.544, 95% confidence interval = 2.151-142.860, P = 0.008). The optimal cutoff point of cIMT for discriminating these two clinical states was 0.6 mm yielding a sensitivity of 61.5% and a specificity of 59.6%. CONCLUSION Individuals with MetS demonstrated increased cIMT values compared with those without MetS. However, high plasma fibrinogen level may not be associated with MetS state. PMID:25477980

  8. Relationship between Physical Activity and Plasma Fibrinogen Concentrations in Adults without Chronic Diseases

    PubMed Central

    Gomez-Marcos, Manuel A.; Recio-Rodríguez, José I.; Patino-Alonso, Maria C.; Martinez-Vizcaino, Vicente; Martin-Borras, Carme; de-la-Cal-dela-Fuente, Aventina; Sauras-Llera, Ines; Sanchez-Perez, Alvaro; Agudo-Conde, Cristina; García-Ortiz, Luis

    2014-01-01

    Objective To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR), and plasma fibrinogen concentrations. Methods A cross-sectional study in a previously established cohort of healthy subjects was performed. This study analyzed 1284 subjects who were included in the EVIDENT study (mean age 55.0±13.6 years; 60.90% women). Fibrinogen concentrations were measured in blood plasma. Physical activity was assessed with a 7-day PAR (metabolic equivalents (METs)/hour/week) and GT3X ActiGraph accelerometer (counts/minute) for 7 days. Results Physical exercise, which was evaluated with both an accelerometer (Median: 237.28 counts/minute) and 7-day PAR (Median: 8 METs/hour/week). Physical activity was negatively correlated with plasma fibrinogen concentrations, which was evaluated by counts/min (r = −0.100; p<0.001) and METs/hour/week (r = −0.162; p<0.001). In a multiple linear regression analysis, fibrinogen concentrations of the subjects who performed more physical activity (third tertile of count/minute and METs/hour/week) respect to subjects who performed less (first tertile), maintained statistical significance after adjustments for age and others confounders (β = −0.03; p = 0.046 and β = −0.06; p<0.001, respectively). Conclusions Physical activity, as assessed by accelerometer and 7-day PAR, was negatively associated with plasma fibrinogen concentrations. This relation is maintained in subjects who performed more exercise even after adjusting for age and other confounders. PMID:24498413

  9. Congenital fibrinogen disorders: an update.

    PubMed

    de Moerloose, Philippe; Casini, Alessandro; Neerman-Arbez, Marguerite

    2013-09-01

    Hereditary fibrinogen abnormalities comprise two classes of plasma fibrinogen defects: Type I, afibrinogenemia or hypofibrinogenemia, which has absent or low plasma fibrinogen antigen levels (quantitative fibrinogen deficiencies), and Type II, dysfibrinogenemia or hypodysfibrinogenemia, which shows normal or reduced antigen levels associated with disproportionately low functional activity (qualitative fibrinogen deficiencies). In afibrinogenemia and hypofibrinogenemia, most mutations of the FGA, FGB, or FGG fibrinogen encoding genes are null mutations. In some cases, missense or late truncating nonsense mutations allow synthesis of the corresponding fibrinogen chain but intracellular fibrinogen assembly and/or secretion are impaired. Afibrinogenemia is associated with mild-to-severe bleeding, whereas hypofibrinogenemia is most often asymptomatic. Thromboembolism may occur either spontaneously or in association with fibrinogen substitution therapy. Women with afibrinogenemia suffer from recurrent pregnancy loss but this can also occur in women with hypofibrinogenemia. Dysfibrinogenemia, caused mainly by missense mutations, is commonly associated with bleeding, thrombophilia, or both; however, most individuals are asymptomatic. Hypodysfibrinogenemia is a subcategory of this disorder. Even in specialized laboratories, the precise diagnosis of some fibrinogen disorders may be difficult. Determination of the molecular defects is important because it gives the possibility to confirm the diagnosis, to elaborate a diagnostic strategy, to distinguish in some cases that the patient is at risk of thrombosis rather than bleeding, and to enable prenatal diagnosis. However, genotype-phenotype correlations are not easy to establish. Replacement therapy is effective in treating bleeding episodes, but because the pharmacokinetics of fibrinogen after replacement therapy is highly variable among patients, it is important to adjust the treatment individually. Thieme Medical Publishers

  10. Interaction between Fibrinogen and Insulin-Like Growth Factor-Binding Protein-1 in Human Plasma under Physiological Conditions.

    PubMed

    Gligorijević, N; Nedić, O

    2016-02-01

    Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role.

  11. Aronia melanocarpa extract suppresses the biotoxicity of homocysteine and its metabolite on the hemostatic activity of fibrinogen and plasma.

    PubMed

    Malinowska, Joanna; Babicz, Karolina; Olas, Beata; Stochmal, Anna; Oleszek, Wieslaw

    2012-07-01

    Aronia melanocarpa fruits (Rosaceae) are one of the richest plant sources of phenolic substances, and it has been shown to have various biological activities. Berries of A. melanocarpa (chokeberry) have been supposed to be beneficial for the prevention of cardiovascular events. In this study the influence of aronia extract on the clot formation (using human plasma and purified fibrinogen) and the fibrin lysis during the model of hyperhomocysteinemia was investigated. Hyperhomocysteinemia was induced using a reduced form of Hcys (at final dose of 0.1mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). The aim of our study in vitro was also to investigate the modifications of human plasma total proteins and the oxidative stress (by measuring the total antioxidant level - TAS) in plasma after incubation with Hcys, HTL and/or aronia extract. The biological properties of aronia extract were compared with the action of a well characterized antioxidative commercial polyphenol - resveratrol (3,4',5- trihydroxystilbene). The HTL, like its precursor, Hcys stimulated polymerization of fibrinogen. The results also demonstrated that Hcys (0.1mM) and HLT at lower doses than Hcys (1 μM) reduced the fibrin lysis in human plasma. Moreover, Hcys and HTL change the level of thiol and amino groups in plasma total proteins and induce the oxidative stress in plasma. Our results indicate that aronia extract reduced the biotoxicity action of Hcys and HTL on hemostatic properties of fibrinogen or plasma, suggesting its possible protective properties in hyperhomocysteinemia - induced cardiovascular diseases. Moreover, our results showed that the extract from berries of A. melanocarpa due to antioxidant action, significantly reduced the oxidative stress (measured by TAS) in plasma during the model of hyperhomocysteinemia. In the comparative studies, the extract from berries of A. melanocarpa and reseveratrol had similar protective properties

  12. Degradation of Human Fibrinogen by Plasma α2-Macroglobulin-Enzyme Complexes

    PubMed Central

    Harpel, Peter C.; Mosesson, Michael W.

    1973-01-01

    This study demonstrates that human plasma α2-macroglobulin preparations possess an enzymic activity that degrades fibrinogen, resulting in the formation of products whose structure resembles that of circulating fibrinogen catabolites. The sequence of degradation is similar to that observed in plasmin-catalyzed digests, in that Aα-chain fragmentation precedes that of Bβ-chain. The addition of plasminogen activators to plasma induced an increase in the N-α-tosyl-l-arginine methyl ester HCl esterase and fibrinogenolytic activity associated with α2-macroglobulin purified from this plasma, indicating that the enzymic activity of the complex was preserved and could be increased in the presence of other plasma enzyme inhibitors. Immunochemical studies demonstrated that an α2-macroglobulin-plasmin complex had formed in urokinase-treated plasma. This α2-macroglobulin preparation manifested an esterolytic profile like that of a complex prepared from plasmin and purified α2-macroglobulin. After complex formation with α2-macroglobulin in plasma, plasmin retained less than 0.1% of its fibrinogenolytic activity. That plasmin expressed its activity while bound to α2-macroglobulin was suggested by immunoprecipitation of this activity with α2-macroglobulin antibody and by the demonstration that pancreatic trypsin inhibitor did not effectively inhibit its fibrinogenolytic or esterolytic activity. These results raise the possibility that, in addition to its activity as a major plasma proteolytic enzyme inhibitor, α2-macroglobulin may modulate enzyme-substrate interactions, such as those resulting in the formation of circulating fibrinogen catabolites, by providing a mechanism for the preservation and protection of a portion of the enzymic activity in the presence of other circulating inhibitors. Images PMID:4269529

  13. Carpal tunnel syndrome is associated with high fibrinogen and fibrinogen deposits.

    PubMed

    Utrobičić, Ivan; Novak, Ivana; Marinović-Terzić, Ivana; Matić, Katarina; Lessel, Davor; Salamunić, Ilza; Babić, Mirna Saraga; Kunac, Nenad; Mešin, Anka Koštić; Kubisch, Christian; Maček, Boris; Terzić, Janoš

    2014-09-01

    Idiopathic carpal tunnel syndrome (ICTS) is a common entrapment neuropathy. Some cases of ICTS are linked to mutations of the transthyretin gene, whereas others are associated with systemic amyloidosis. The majority of ICTS cases are of unknown etiology. To study molecular mechanisms of ICTS development. A total of 71 ICTS patients and 68 control subjects were included in the study. The fibrinogen level was determined before surgery and its deposition in the transversal carpal ligament (TCL) was detected by immunohistochemistry, Western blot, and mass spectrometry. Fibrinogen interaction with other proteins was studied by immunoprecipitation assay. Plasma levels of the proinflammatory and hemostatic protein fibrinogen are elevated in ICTS patients. Other measured systemic inflammatory markers were not affected, and local inflammatory responses in TCL were absent. ICTS patients have shorter bleeding times, probably because of the elevated plasma levels of fibrinogen. Polymorphisms of the fibrinogen B promoter region were previously associated with increased plasma fibrinogen, but this association was not observed among patients with ICTS. Interestingly, we detected fibrinogen deposits in the TCL, whereas transcriptional activity of the fibrinogen genes was low. Amyloidogenic proteins, including transthyretin and α-synuclein, were also found in the TCL, whereas their local transcriptional activity was rather high. Finally, we demonstrated that fibrinogen interacts with transthyretin and α-synuclein in TCL lysates. Our data indicate that fibrinogen and other aggregation-prone proteins have potentially important roles in the pathogenesis of ICTS.

  14. Baseline and long-term fibrinogen levels and risk of sudden cardiac death: A new prospective study and meta-analysis.

    PubMed

    Kunutsor, Setor K; Kurl, Sudhir; Zaccardi, Francesco; Laukkanen, Jari A

    2016-02-01

    Inflammatory markers such as C-reactive protein (CRP) and interleukin-6 have been linked with an increased risk of sudden cardiac death (SCD), but the relationship between fibrinogen and SCD is uncertain. We aimed to assess the association between fibrinogen and SCD. Plasma fibrinogen was measured at baseline in a prospective cohort of 1773 men aged 42-61 years free of heart failure or cardiac arrhythmias, that recorded 131 SCDs during 22 years follow-up. Correction for within-person fibrinogen variability was made using data from repeat measurements taken several years apart. Fibrinogen was strongly correlated with CRP, weakly correlated with several cardiovascular risk markers, and was log-linearly associated with SCD risk. In analyses adjusted for conventional risk factors, the hazard ratio (HR) (95% CIs) for SCD per 1 standard deviation (SD) higher baseline loge fibrinogen was 1.32 (1.11-1.57). The results remained consistent on further adjustment for alcohol consumption, resting heart rate, and circulating lipids 1.30 (1.09-1.56). The corresponding HRs were 1.80 (1.25-2.58) and 1.74 (1.20-2.52) after correction for within-person variability. HRs remained unchanged on further adjustment for CRP and accounting for incident coronary events. In a meta-analysis of three cohort studies, the fully-adjusted relative risks for SCD per 1 SD higher baseline and long-term fibrinogen levels were 1.42 (1.25-1.61) and 2.07 (1.59-2.69) respectively. The associations were similar for non-SCDs in both cohort analysis and the meta-analysis. Addition of plasma fibrinogen to a SCD risk prediction model containing established risk factors did not significantly improve risk discrimination, but improved the net reclassification. Available data suggest fibrinogen is positively, log-linearly, and independently associated with risk of SCD. Further research is needed to assess the potential relevance of plasma fibrinogen concentrations in SCD prevention. Copyright © 2015 Elsevier

  15. The Role of Serum Fibrinogen Level in the Diagnosis of Acute Appendicitis

    PubMed Central

    Nyuwi, Kuotho T; Khumukcham, Sridartha; Rangaswamy, Raju; Ezung, Yibenthung S; Chittvolu, Sowdin Reddy; Sharma, A Barindra; Singh, H Manihar

    2017-01-01

    Introduction Acute appendicitis is the most common indication for emergent surgery and affects a wide range of patients at any age group. However, inspite of the presence of various imaging modalities, biochemical markers, and scoring systems the negative appendectomy rate remain high. Serum fibrinogen, an acute inflammatory mediator is usually raised in any acute inflammatory condition and the same is expected to rise in acute appendicitis, which may be used as a new inflammatory marker in the diagnosis and more importantly in decision making of management of acute appendicitis. Aim To determine the relationship between the rise in the level of serum fibrinogen and acute appendicitis and its role in reducing the negative appendectomy rate. Materials and Methods A total of 82 patients with clinical signs and symptoms of acute appendicitis who underwent emergency appendectomy were included in the study, the serum fibrinogen level were measured just before the operation and the sensitivity and the specificity was calculated. The final diagnosis was based on the histopathological examination. Results In our study, the Mean±SD of serum fibrinogen in mg/dl in those patient proved to be having acute appendicitis by histopathology was 436.6±40.6 while those with normal appendix was 391.91±66.54. The area under the curve was 0.697 i.e., it has an accuracy of around 70% and this is statistically significant (p=0.018). On further sub-analysis when the cut off level of fibrinogen level was reduced to 397, it resulted in a sensitivity of 82% and specificity of 60% and if the level was further reduced to 375 it increased the sensitivity to 88% with a specificity of 55%. Conclusion In the diagnosis of acute appendicitis, use of fibrinogen blood level may be a new diagnostic acute-phase reactant with possible role in reducing negative appendectomy rate. PMID:28274001

  16. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma.

    PubMed

    Harr, Jeffrey N; Moore, Ernest E; Ghasabyan, Arsen; Chin, Theresa L; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C

    2013-01-01

    Thromboelastography (TEG) is emerging as the standard in the management of acute coagulopathies in injured patients. Although TEG is sensitive in detecting abnormalities in clot strength, one shortcoming is differentiating between fibrinogen and platelet contributions to clot integrity. Current American algorithms suggest platelet transfusion, whereas European guidelines suggest fibrinogen concentrates for correcting low clot strength. Therefore, we hypothesized that a TEG-based functional fibrinogen (FF) assay would assess the contribution of fibrinogen and platelets to clot strength and provide insight to transfusion priorities. Blood samples were obtained from trauma patients on arrival to the emergency department or who were admitted to the surgical intensive care unit (n = 68). Citrated kaolin TEG, FF, and von Clauss fibrinogen levels (plasma-based clinical standard) were measured. Correlations were assessed using linear regression models. In vitro studies were also performed with adding fibrinogen concentrates to blood collected from healthy volunteers (n = 10). Functional fibrinogen and citrated kaolin TEG parameters were measured. Functional fibrinogen strongly correlated with von Clauss fibrinogen levels (R = 0.87) and clot strength (R = 0.80). The mean fibrinogen contribution to clot strength was 30%; however, there was a direct linear relationship with fibrinogen level and percent fibrinogen contribution to clot strength (R = 0.83). Traditional TEG parameters associated with fibrinogen activity (α angle and kinetic time) had significantly lower correlations with FF (R = 0.70 and 0.35). Furthermore, platelet count had only a moderate correlation to clot strength (R = 0.51). The addition of fibrinogen concentrate in in vitro studies increased clot strength (MA) (60.44 ± 1.48 to 68.12 ± 1.39) and percent fibrinogen contribution to clot strength (23.8% ± 1.8% to 37.7% ± 2.5%). Functional fibrinogen can be performed rapidly with TEG and correlates well

  17. Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol.

    PubMed

    Belcaro, G; Cesarone, M R; Errichi, S; Zulli, C; Errichi, B M; Vinciguerra, G; Ledda, A; Di Renzo, A; Stuard, S; Dugall, M; Pellegrini, L; Gizzi, G; Ippolito, E; Ricci, A; Cacchio, M; Cipollone, G; Ruffini, I; Fano, F; Hosoi, M; Rohdewald, P

    2008-01-01

    In a previous, double-blind, placebo-controlled study we evaluated the efficacy of a 3-month treatment with Pycnogenol for 156 patients with osteoarthritis of the knee. Pycnogenol significantly decreased joint pain and improved joint function as evaluated using the WOMAC score and walking performance of patients on a treadmill. In this study, we further investigated the anti-inflammatory and antioxidant activity of Pycnogenol in a subset of the osteoarthritis patients presenting with elevated C-reactive protein (CRP) and plasma-free radicals. Elevated CRP levels have been suggested to be associated with disease progression in osteoarthritis. In our study, 29 subjects of the Pycnogenol group and 26 patients in the placebo group showed CRP levels higher than 3 mg/l at baseline. Comparison of blood specimens drawn at baseline and after 3-month treatment showed that Pycnogenol significantly decreased plasma free radicals to 70.1% of baseline values. Plasma CRP levels decreased from baseline 3.9 mg/l to 1.1 mg/l in the Pycnogenol group whereas the control group had initial values of 3.9 mg/l which decreased to 3.6 mg/l. The CRP decrease in the Pycnogenol was statistical significant as compared to the control group (P < 0.05). Fibrinogen levels were found to be lowered to 62.8% of initial values (P < 0.05) in response to Pycnogenol. No significant changes for plasma free radicals, CRP and fibrinogen were found in the placebo-treated group. The decrease of systemic inflammatory markers suggests that Pycnogenol may exert anti-inflammatory activity in osteoarthritic joints and patients did not present with other ailments or infections. The nature of the anti-inflammatory effects of Pycnogenol with regard to CRP warrants further investigation.

  18. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows.

    PubMed

    Brust, M; Aouane, O; Thiébaud, M; Flormann, D; Verdier, C; Kaestner, L; Laschke, M W; Selmi, H; Benyoussef, A; Podgorski, T; Coupier, G; Misbah, C; Wagner, C

    2014-03-11

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

  19. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    PubMed Central

    Brust, M.; Aouane, O.; Thiébaud, M.; Flormann, D.; Verdier, C.; Kaestner, L.; Laschke, M. W.; Selmi, H.; Benyoussef, A.; Podgorski, T.; Coupier, G.; Misbah, C.; Wagner, C.

    2014-01-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects. PMID:24614613

  20. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    NASA Astrophysics Data System (ADS)

    Brust, M.; Aouane, O.; Thiébaud, M.; Flormann, D.; Verdier, C.; Kaestner, L.; Laschke, M. W.; Selmi, H.; Benyoussef, A.; Podgorski, T.; Coupier, G.; Misbah, C.; Wagner, C.

    2014-03-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

  1. Four-Group Classification Based on Fibrinogen Level and Fibrin Polymerization Associated With Postoperative Bleeding in Cardiac Surgery.

    PubMed

    Kawashima, Shingo; Suzuki, Yuji; Sato, Tsunehisa; Kikura, Mutsuhito; Katoh, Takasumi; Sato, Shigehito

    2016-10-01

    Fibrinogen and fibrin formation have a key role in perioperative hemostasis. The aim of this study is to examine the association of postoperative hemostasis with a combined evaluation of the fibrinogen level and fibrin polymerization in cardiac surgery. We retrospectively classified 215 consecutive cardiac surgery patients into 4 groups (Fuji-san classification) that were divided by fibrinogen level <150 mg/dL (ie, hypofibrinogenemia) and fibrinogen thromboelastometry value at 10 minutes with rotational thromboelastometry <6 mm (ie, low fibrin polymerization) at the warming of cardiopulmonary bypass. Four groups resulted; group I, the acceptable range (n = 85); group II, only hypofibrinogenemia (<150 mg/dL, ≥6 mm, n = 63); group III, hypofibrinogenemia and low fibrin polymerization (<150 mg/dL, <6 mm, n = 60); and group IV, only low fibrin polymerization (≥150 mg/dL, <6 mm, n = 7). The risk of chest tube drainage volume greater than 500 mL within the first 24 hours after surgery (with group I as the reference) was increased in group II (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.4; P < .01) and group III (OR, 8.5; 95% CI, 3.5-21.7; P < .01), and the risk greater than 1000 mL (with group I as the reference) was increased in group III (OR, 4.0; 95% CI, 1.1-17.3; P = .03) and group IV (OR, 23.1; 95% CI, 3.2-201.0; P < .01). Intraoperative blood transfusions were decreased by 24.5%, after stratifying the starting amount of fresh frozen plasma by the 4-group classification in the recent consecutive 65 (30.2%) patients (P < .01). The 4-group classification is associated with postoperative bleeding and may improve the quality of perioperative blood transfusion in cardiac surgery.

  2. Determining the effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration in rat plasma samples.

    PubMed

    Goyal, Vinod Kumar; Kakade, Somesh; Pandey, Santosh Kumar; Gothi, Anil Kalidas; Nirogi, Ramakrishna

    2015-10-01

    Coagulation parameters are usually included in clinical and preclinical safety studies to evaluate the effect of xenobiotics on the extrinsic or intrinsic pathways of coagulation. The analysis is generally performed at the time of terminal sacrifice where many activities are scheduled. Chances of delay in analysis are likely particularly when blood is collected for coagulation via the abdominal vena cava. This experiment was planned to assess the variations in coagulation parameters caused by delay in analysis as well as by storage conditions. Blood was collected from the posterior vena cava under isoflurane anesthesia, and the plasma was separated immediately. Coagulation parameters were evaluated at 0, 6, 24 and 48 h from the plasma stored at room temperature, as well as plasma stored under refrigerated and freezing conditions. Stability of the analytes in blood was also evaluated under refrigerated conditions for 6 h. All parameters were analyzed using a semi-automated coagulometer. Prothrombin time (PT) was stable under all three storage conditions for up to 6 h. Although statistically significant differences were observed for activated partial thromboplastin time (APTT) at room and refrigeration temperatures for up to 6 h, the difference was clinically non-relevant. Fibrinogen was found to be the most stable parameter that showed consistency in results even up to 48 h under all three storage conditions. Plasma for PT can be stored and analyzed without any significant changes for up to 6 h from the actual blood collection, while fibrinogen level testing can be extended for up to 48 h after collection under any storage condition. For reliable APTT results, plasma samples should be run immediately after collection.

  3. Physical functioning related to C-reactive protein and fibrinogen levels in mid-life women

    PubMed Central

    Tomey, Kristin; Sowers, MaryFran; Zheng, Huiyong; Jackson, Elizabeth A.

    2009-01-01

    We investigated whether subclinical inflammatory markers high-sensitivity C-reactive protein (CRP) and fibrinogen are related to measures of physical functioning in midlife women. Our sample included 543 participants in the Michigan site of Study of Women’s Health Across the Nation (SWAN). Predictors included CRP from serum and fibrinogen from plasma. Performance-based outcomes included measures of gait, hand grip strength, flexibility, stair climb, 40-foot walk, and chair rise. Perception of physical functioning was assessed with the Medical Outcomes Study Short-Form 36 questionnaire. Regression analyses adjusted for relevant covariates. Cross-sectional associations were identified between higher CRP and more time spent in double support (with both feet on the floor while walking), shorter forward reach, slower 2-lb lift, and slower stair climb. Higher CRP and fibrinogen were associated with worse perceived functioning in cross-sectional analyses. Predictive associations across time were found between higher CRP and increased time spent in double support, diminishing forward reach distance and grip strength and worse perceived physical functioning. Predictive associations across time were also found between higher fibrinogen and greater time spent in double support, slower stair climb and worse perceived physical functioning. Our results suggest that inflammatory processes are associated with poor physical functioning in midlife women. PMID:19819323

  4. Evaluation of urine fibrinogen level in a murine model of contrast-induced nephropathy.

    PubMed

    Yao, Luyu; Dong, Honglin; Zhao, Cynthia X; Gu, Xin; Tan, Tze-W; Hamidian Jahromi, Alireza; Zhang, Wayne W

    2016-06-01

    The mechanisms of contrast-induced nephropathy are not fully understood and sensitive biomarkers of contrast-induced nephropathy are yet to be found. We investigated whether urinary fibrinogen could be a potential biomarker for contrast-induced nephropathy. To create a contrast-induced nephropathy model, mice received a prostaglandin synthesis inhibitor (indomethacin) and a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine methyl ester) intraperitoneally followed by a different dose of iodixanol. In the control group, normal saline was administered. Urinary fibrinogen and serum creatinine were analyzed using enzyme-linked immunosorbent assay. Kidneys were used to quantify fibrinogen using qRT-PCR and Western blot and for histopathological examination. Histopathological examination demonstrated mild renal injury in the low-dose group, and moderate renal injury in the high-dose group. Urinary fibrinogen levels were significantly increased in an iodixanol dose-dependent manner (control vs. low-dose group, P < 0.05; control vs. high-dose group P < 0.01). Serum creatinine levels were only increased in the high-dose group (P < 0.01 compared to control), but not in the low-dose group. For fibrinogen-gene expression, in the low-dose group, Fgγ increased (qRT-PCR, Western blot, P < 0.05) in the high-dose group, Fgβ and Fgγ decreased (qRT-PCR, P < 0.01; Western blot, P < 0.05), and Fgα increased (qRT-PCR, P < 0.05; Western blot, P < 0.05). We propose that urinary fibrinogen could be used as a potential biomarker for early contrast-induced nephropathy diagnosis. © The Author(s) 2015.

  5. Interaction of platelets, fibrinogen and endothelial cells with plasma deposited PEO-like films

    NASA Astrophysics Data System (ADS)

    Yang, Zhilu; Wang, Jin; Li, Xin; Tu, Qiufen; Sun, Hong; Huang, Nan

    2012-02-01

    For blood-contacting biomedical implants like retrievable vena cava filters, surface-based diagnostic devices or in vivo sensors, limiting thrombosis and cell adhesion is paramount, due to a decrease even failure in performance. Plasma deposited PEO-like films were investigated as surface modifications. In this work, mixed gas composed of tetraethylene glycol dimethyl ether (tetraglyme) vapor and oxygen was used as precursor. It was revealed that plasma polymerization under high ratio of oxygen/tetraglyme led to deposition of the films that had high content of ether groups. This kind of PEO-like films had good stability in phosphate buffer solution. In vitro hemocompatibility and endothelial cell (EC) adhesion revealed low platelet adhesion, platelet activation, fibrinogen adhesion, EC adhesion and proliferation on such plasma deposited PEO-like films. This made it a potential candidate for the applications in anti-fouling surfaces of blood-contacting biomedical devices.

  6. Fibrinogen Brescia

    PubMed Central

    Brennan, Stephen O.; Wyatt, Jane; Medicina, Daniela; Callea, Francesco; George, Peter M.

    2000-01-01

    The proposita suffered from liver cirrhosis and biopsy showed type 1 membrane-bound fiberglass inclusions. The hepatic inclusion bodies were weakly periodic acid-Schiff diastase-positive, and on immunoperoxidase staining reacted specifically with anti-fibrinogen antisera. Coagulation investigations revealed low functional and antigenic fibrinogen together with a prolonged thrombin time of 37 seconds (normal, 17 to 22 seconds) suggestive of a hypodysfibrinogenemia. DNA sequencing of all three fibrinogen genes showed a single heterozygous mutation of GGG (Gly)→CGG (Arg) at codon 284 of the γ-chain gene. However, examination of purified fibrinogen chains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reverse-phase high-performance liquid chromatography, ion-exchange high-performance liquid chromatography, and isoelectric focusing, failed to show any evidence of the mutant γBr chain in plasma fibrinogen. This finding was substantiated by electrospray ionization mass spectrometry, which showed only a normal γ (and Bβ) chain mass, but a large increase in the portion of their disialo isoforms. We speculate that misfolding of the variant protein causes hepatic retention and the subsequent hypofibrinogenemia, and that the functional defect (dysfibrinogenemia) results from hypersialylation of otherwise normal Bβ and γ chains consequent to the liver cirrhosis. These conclusions were supported by studies on six other family members with hypofibrinogenemia, and essentially normal clotting times, who were heterozygous for the γ284 Gly→Arg mutation. PMID:10880389

  7. Label-Free Quantitative Immunoassay of Fibrinogen in Alzheimer Disease Patient Plasma Using Fiber Optical Surface Plasmon Resonance

    NASA Astrophysics Data System (ADS)

    Kim, Jisoo; Kim, SeJin; Nguyen, Tan Tai; Lee, Renee; Li, Tiehua; Yun, Changhyun; Ham, Youngeun; An, Seong Soo A.; Ju, Heongkyu

    2016-05-01

    We present a real-time quantitative immunoassay to detect fibrinogen in the blood plasma of Alzheimer's disease patients using multimode fiber optical sensors in which surface plasmon resonance (SPR) was employed. Nanometer-thick bimetals including silver and aluminum were coated onto the core surface of the clad-free part (5 cm long) of the fiber for SPR excitation at the He-Ne laser wavelength of 632.8 nm. The histidine-tagged peptide was then coated on the metal surface to immobilize the fibrinogen antibody for the selective capture of fibrinogen among the proteins in the patient blood plasma. The SPR fiber optical sensor enabled quantitative detection of concentrations of fibrinogen from the different human patient blood at a detection limit of ˜20 ng/ml. We also observed a correlation in the fibrinogen concentration measurement between enzyme-linked immunosorbent assay and our SPR fiber-based sensors. This suggests that the presented SPR fiber-based sensors that do not rely on the use of labels such as fluorophores can be used for a real-time quantitative assay of a specific protein such as fibrinogen in a human blood that is known to contain many other kinds of proteins together.

  8. Intermediate-Risk Chronic Stable Angina: Neutrophil-Lymphocyte Ratio and Fibrinogen Levels Improved Predicting Angiographically-Detected Coronary Artery Disease

    PubMed Central

    Haybar, Habib; Ahmadzadeh, Ahmad; Assareh, Ahmadreza; Afshari, Nader; Bozorgmanesh, Mohammadreza; Vakili, Mahdis

    2016-01-01

    Background Coronary heart disease (CHD) is the leading cause of death worldwide. Research indicates that coronary atherosclerosis is the most frequent cause of CHD. Evidence is scarce concerning the clinical efficacy of fibrinogen or neutrophil-lymphocyte ratio (NLR) measurement in risk-stratifying patients with chronic stable angina. Objectives To examine the independent and incremental prognostic value of fibrinogen and neutrophil-lymphocyte ratio (NLR) for angiographically-detected coronary artery disease (CAD). Patients and Methods In this cross-sectional study, angiography was performed for 183 Iranian patients with chronic stable angina with exercise ECG-determined intermediate risk. Generalized estimated equations were used to obtain the odd ratio (OR) of CAD for a 1-unit increase in log-NLR and a 1-SD increase in plasma fibrinogen. Models were adjusted for established CAD risk factors. Integrated discriminatory improvement index (IDI) and net reclassification improvement index (NRI) were used as measures of predictive ability for CAD, combined with traditional risk factors by NLR and fibrinogen. Results The mean age of the participants was 57.5, with 51.9% being male. Only 12% of participants had angiographically-determined patent coronary arteries. The number of participants with one, two, and three-vessel stenosis were 76, 31, 31, respectively, while 45 did not have stenosed vessels. NLR and fibrinogen levels were significantly higher in patients with stenosis in two (2.4 and 512 mg.dL-1) or three (2.6 and 517 mg.dL-1) coronary arteries, as compared to the group of patients with no significant involvement (2 and 430 mg.dL-1) (all P < 0.01). Patients with a higher NLR and a higher fibrinogen levels were more likely to have higher grades of CAD. OR log-NLR = 1.36 (95% CI: 1.05 - 1.94) and OR Z-Fibrinogen = 1.61 (95% CI: 1.18 - 2.22). When NLR and fibrinogen were added to the traditional risk factors separately, the NRIs were 0.170 (0.023 - 0.324) and 0

  9. Fibrinogen Oviedo I. A new Spanish dysfibrinogenaemia.

    PubMed

    Fernández, F J; Rodríguez Pinto, C; Páramo, J; Cuesta, B; Collado, M; Rocha, E

    1990-10-01

    An abnormal fibrinogen was discovered in the plasma of a clinically asymptomatic woman. Laboratory evaluation of five members of the affected family showed low fibrinogen values in kinetic assays whereas the fibrinogen levels, tested by immunological procedures were normal. The patient's plasma had an inhibitory effect on the thrombin time of normal plasma. The calcium ions totally corrected the thrombin and reptilase times. Either low or high ionic strength prolonged the thrombin time of the proposita's purified fibrinogen. Kinetic analysis of clotting by monitoring transmission at 350 nm showed abnormally slow clotting with thrombin and reptilase. Assays were preformed in whole plasma as well as in purified fibrinogen. A delay in the rate of polymerization was evident when purified patient monomers were compared with those of normals. Immunoelectrophoretic, chromatofocusing, and isoelectrofusing experiments detected neither structural nor immunological abnormalities of fibrinogen. The rate of release of fibrinopeptide A by thrombin, measured by a specific immunoenzymatic method was also normal. HPLC analysis showed normal liberation of fibrinopeptides after prolonged thrombin action. Cross-linking of fibrin by factor XIII and lysis of fibrinogen by plasmin were normal. In view of these results, the defect of this dysfibrinogenemia, designated as Fibrinogen Oviedo I, probably could be due to conformational modifications in the D section of the molecule.

  10. Signal transduction pathways in erythrocyte nitric oxide metabolism under high fibrinogen levels

    NASA Astrophysics Data System (ADS)

    Saldanha, Carlota; Freitas, T.; Lopez de Almeida, J. P.; Silva-Herdade, A.

    2014-05-01

    Previous studies show that the fibrinogen molecule modulates the metabolism of nitric oxide (NO) in erythrocyte. The in vitro induced hiperfibrinogenemia interferes in the metabolism of the NO in the erythrocyte in dependence of the phosphorylation degree of the band 3. The soluble form of fibrinogen binds into CD47 protein present in the erythrocyte membrane. The soluble thrombomodulin is an inflammatory marker that binds to the erythrocyte CD47 in a site with a sequence peptide known as 4N1K. A study done in vitro shows that when hiperfibrinogenemia was induced in the presence of the peptide 4N1K agonist of CD47 it were observed variations in the efflux of NO from erythrocyte and an increase in the concentrations of GSNO, peroxinitrite, nitrite and nitrate of the erythrocytes. The aim of this work was to study the influence of the peptide 4N1K, on the metabolism of NO in the erythrocyte under high fibrinogen concentration and in the presence of inhibitors of the status of phosphorylation of protein band 3. In this in vitro study, whole blood samples were harvested from healthy subjects and NO, peroxynitrite, nitrite, nitrate and S-nitro-glutathione (GSNO) were determined in presence of 4N1K, calpeptine, Syk inhibitor and under high fibrinogen concentrations. The results obtained in erythrocytes under high fibrinogen levels when 4N1K is present with the Syk inhibitor or with calpeptine, showed in relation to the control samples increased significant concentrations of efflux of NO and of peroxynitrite, nitrite, nitrate and GSNO. In conclusion it was verified that in the in vitro model of hiperfibrinogenemia the peptide 4N1K, agonist of CD47, induces mobilization of NO in the erythrocyte in dependence of the status of phosphorylation of protein band 3.

  11. Serum fibrinogen levels could be an index of successful use of balloon tamponade in postpartum hemorrhage.

    PubMed

    Nakashima, Ayaka; Ogita, Kazuhide; Chita, Masaya; Yokoi, Takeshi

    2017-02-28

    The object of our study was to determine whether serum fibrinogen levels could be used to predict the success rates of balloon tamponade and decrease the use of invasive methods. This retrospective study, conducted at Rinku General Medical Center, was aimed to identify factors associated with high success rates in balloon tamponade. Forty-six patients with postpartum hemorrhage (PPH), non-responsive to uterotonics and treated with balloon tamponade between April 2008 and March 2015, were included. Forty-six women were included, of which 34 underwent vaginal delivery and 12 underwent cesarean delivery. There were no complications from balloon tamponade and its success rate was 73.3%. Seven women required additional procedures: One used gauze packing, three used uterine artery embolization, and five underwent peripartum hysterectomy. The cut-off line of serum fibrinogen level was 172.5 mg/dL (P=0.002) with its 77.4% sensitivity and 66.7% specificity. We recommend measuring serum fibrinogen level for predicting whether the balloon tamponade can be used successfully or not.

  12. Fibrinogen replacement therapy for congenital fibrinogen deficiency.

    PubMed

    Bornikova, L; Peyvandi, F; Allen, G; Bernstein, J; Manco-Johnson, M J

    2011-09-01

    This review of published studies was conducted to derive data on patients with congenital fibrinogen deficiency (CFD), including dosing of fibrinogen replacement therapy, outcome, and adverse events, either temporally related or distant to fibrinogen replacement, in order to assist clinicians in developing treatment plans for patients with CFD. A systematic review was performed of case reports identified by a MEDLINE search between 1961 and 2010. Eligible studies included subjects with a diagnosis of CFD who received fibrinogen replacement. An attempt was made to extract dose, frequency, duration, hemostatic efficacy and adverse events such as thrombosis or allergic reactions. Reported thrombotic events distant from fibrinogen replacement were also recorded. From 104 papers reviewed, a total of 50 cases were identified: afibrinogenemia (35), hypofibrinogenemia (6), and dysfibrinogenemia (9). Fibrinogen replacement therapy was generally effective in preventing or treating bleeding in doses adequate to achieve and maintain fibrinogen activity above 50-100 mg dL(-1) (non-surgical and obstetric use) or 100-200 mg dL(-1) (surgical prophylaxis). Increased fibrinogen clearance was observed with massive hemorrhage, major surgery, and advanced pregnancy. Obstetric outcomes were optimized when fibrinogen replacement was initiated prior to conception. Uncontrolled hemorrhage, allergic reactions and antibody formation were rare events. However, thromboses, both related and unrelated to fibrinogen replacement, occurred in 15 of 50 (30%) patients overall, and in eight of 12 (67%) adult non-obstetric patients with afibrinogenemia. Published fibrinogen replacement regimens are presented for 50 CFD patients. Fibrinogen replacement therapy requires careful monitoring of fibrinogen levels. Afibrinogenemia is associated with thromboembolic complications with or without treatment. © 2011 International Society on Thrombosis and Haemostasis.

  13. HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL: A MULTICENTER RETROSPECTIVE STUDY.

    PubMed

    Hayakawa, Mineji; Maekawa, Kunihiko; Kushimoto, Shigeki; Kato, Hiroshi; Sasaki, Junichi; Ogura, Hiroshi; Matauoka, Tetsuya; Uejima, Toshifumi; Morimura, Naoto; Ishikura, Hiroyasu; Hagiwara, Akiyoshi; Takeda, Munekazu; Kaneko, Naoyuki; Saitoh, Daizoh; Kudo, Daisuke; Kanemura, Takashi; Shibusawa, Takayuki; Furugori, Shintaro; Nakamura, Yoshihiko; Shiraishi, Atsushi; Murata, Kiyoshi; Mayama, Gou; Yaguchi, Arino; Kim, Shiei; Takasu, Osamu; Nishiyama, Kazutaka

    2016-03-01

    Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38 mg/L)/high fibrinogen (>190 mg/dL), low D-dimer (<38 mg/L)/low fibrinogen (≤190 mg/dL), high D-dimer (≥38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (≥38 mg/L)/low fibrinogen (≤190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.

  14. Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.

    PubMed

    Wei, Naili; Jia, Yanfei; Wang, Xiu; Zhang, Yinian; Yuan, Guoqiang; Zhao, Baotian; Wang, Yao; Zhang, Kai; Zhang, Xinding; Pan, Yawen; Zhang, Jianguo

    2015-01-01

    Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe), longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI), the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with postoperative

  15. Cumulative score based on preoperative plasma fibrinogen and serum C-reactive protein could predict long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Fei; Sun, Peng; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Wu, Jing; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was to establish a prognostic indicator based on preoperative fibrinogen and C-reactive protein (CRP) (FC score) in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative plasma fibrinogen and serum CRP levels were reviewed in patients who underwent transthoracic esophagectomy. The optimal cut-off value for fibrinogen and CRP was defined as 4.0 g/dL and 10.0 mg/L according to previous reports. Patients with elevated fibrinogen and CRP levels were assigned a score of 2, those with only one of these two abnormalities were allocated a score of 1, and those with neither of the two abnormalities were assigned a score of 0. Preoperative FC score was significantly correlated with degree of differentiation, depth of invasion, tumor-node-metastasis (TNM) stage and modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor length, tumor location, lymph node status or smoking were identified between groups. Univariate survival analysis demonstrated that high preoperative FC score (1/2) was significantly associated with impaired disease free survival (DFS) [hazard ratio (HR), 1.650; 95% confidence interval (CI), 1.181-2.303; P = 0.003] and overall survival (OS) (HR, 1.879; 95% CI, 1.333-2.648; P<0.001), and it remained an independent predictor for both DFS (HR, 1.468; 95% CI, 1.043-2.067; P=0.028) and OS (HR, 2.070; 95% CI, 1.266-3.385; P=0.004) in multivariate Cox regression analysis. Preoperative FC score might represent a new potential marker of worst prognosis that warrants further evaluation in prospective and large cohort studies among ESCC patients who underwent transthoracic esophagectomy. PMID:27517497

  16. Removal Dynamics of Immunoglobulin and Fibrinogen by Conventional Plasma Exchange, Selective Plasma Exchange, and a Combination of the Two.

    PubMed

    Miyamoto, Satoko; Ohkubo, Atsushi; Seshima, Hiroshi; Maeda, Takuma; Itagaki, Ayako; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi; Okado, Tomokazu

    2016-08-01

    While plasma exchange (PE) can eliminate plasma proteins, including all immunoglobulin (Ig) and coagulation factors, selective plasma exchange (SePE) can retain fibrinogen (Fbg). Here, we investigated the removal dynamics of Ig and Fbg in 53 patients with immunological disorders by PE, SePE, and a combination of the two. When the mean processed plasma volume (PPV) was 0.9 plasma volume (PV), the mean percent reductions of Ig and Fbg by PE were both approximately 62%-65%. When the mean PPV was 1.1 PV, the mean percent reductions by SePE were 53.1% for IgG, 30.1% for IgA, 3.6% for IgM, and 19.0% for Fbg, respectively. In the three plasmapheresis sessions performed on alternate days, we classified treatments into three categories: PE group (PE-PE-PE, N = 2), SePE group (SePE-SePE-SePE, N = 14), and PE/SePE group (PE-SePE-SePE, N = 4). The mean percent reductions of IgG, IgA, IgM, and Fbg were 82.0%, 80.4%, 87.3%, and 80.9%, respectively, for the PE group; 76.4%, 57.7%, 43.3%, and 35.9%, respectively, for the PE/SePE group; and 75.4%, 50.6%, 3.2%, and 29.3%, respectively, for the SePE group. Plasmapheresis modalities can be combined according to clinical conditions, for instance, to achieve both the unspecific removal of pathogens by PE and retention of coagulation factors, such as Fbg, by SePE.

  17. Serum and plasma latex agglutination tests for detection of fibrin(ogen) degradation products in clinically ill dogs.

    PubMed

    Boisvert, Agatha M.; Swenson, Cheryl L.; Haines, Carolyn J.

    2001-01-01

    An increased concentration of fibrin(ogen) degradation products (FDPs) commonly is used in conjunction with other hemostatic test abnormalities to identify patients with disseminated intravascular coagulation (DIC). Positive FDP results, however, have been observed in dogs without clinical evidence of DIC. The purpose of this study was to evaluate FDP concentrations in a group of clinically ill dogs with a variety of disorders. Dogs included in the study had the following hemostatic parameters evaluated: prothrombin time, activated partial thromboplastin time, fibrinogen concentration, platelet count, and FDP concentration. Two rapid latex agglutination methods were compared for detecting FDP in serum samples (Thrombo-Wellcotest, International Murex Technologies Corp) and plasma samples (FDP Plasma, American Bioproducts Inc). Results of the serum FDP method were positive in 8% (4/50) of the dogs tested: 3 with DIC and 1 with immune-mediated hemolytic anemia and liver disease. Results of the plasma FDP test were positive in 60% (30/50) of the animals tested: 6 with DIC, 3 with confirmed thrombosis, and 21 with a variety of conditions, including neoplasia, immune-mediated hemolytic anemia, pancreatitis, gastric dilatation-volvulus, heat stroke, severe trauma, sepsis, protein-losing nephropathy, liver disease, hyperadrenocorticism, and chronic heart failure. Because the plasma FDP test was positive more frequently than the serum FDP test in ill dogs, it may be more sensitive for the detection of canine FDP.

  18. Effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration on canine plasma samples

    PubMed Central

    Casella, Stefania; Giannetto, Claudia; Giudice, Elisabetta

    2010-01-01

    The present study was to assess the effect of storage conditions on prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration in blood samples of healthy dogs. Thirty-five dogs of various breeds were included in the study. Citrated blood samples were obtained and plasma was divided into four aliquots to assess selected clotting parameters by means of a coagulometer. The first aliquot was analysed within 1 h after collection, while the remaining 3 were stored at 8℃ for 4, 8 and 24 h, respectively. One-way repeated measures analysis of variance documented a significant decreasing effect on PT at 24 h compared to 8 h and on fibrinogen concentration after 8 and 24 h compared to sampling time and at 4 and 24 h compared to 8 h post sampling. In conclusion, the results of this study indicate that only fibrinogen appears prone to significant decrease. In fact, aPTT is not substantially affected by refrigeration for at least 24 h post sampling and PT showed a statistical difference that does not necessary indicate biological significance as the results obtained were within reference intervals for the dog. PMID:20458152

  19. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

    PubMed

    Zhu, Jian-Fei; Cai, Ling; Zhang, Xue-Wen; Wen, Yin-Sheng; Su, Xiao-Dong; Rong, Tie-Hua; Zhang, Lan-Jun

    2014-02-01

    High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  20. Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk.

    PubMed

    Vasse, M; Paysant, J; Soria, J; Collet, J P; Vannier, J P; Soria, C

    1996-10-01

    High level of fibrinogen in plasma is recognised as an important vascular risk factor. However, it is not known if the increase in fibrinogen is directly responsible for the vascular risk or is a marker of vascular inflammation. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since a parallel effect of cytokines on fibrinogen biosynthesis and on vascular injury was noted. Among the cytokines which induce the synthesis of fibrinogen, oncostatin M (OSM) is the most potent cytokine synthesised by activated monocytes for inducing fibrinogen synthesis by Hep G2 cells (human hepatoma cell line). Interestingly at the same concentrations needed for fibrinogen biosynthesis, OSM induces smooth muscle cell proliferation. In contrast, the cytokines IL-4, IL-10 and IL-13 which have a protective effect against vascular injury leading to atherosclerosis, dose dependently down regulate the biosynthesis of fibrinogen. This was due to both a decrease of IL-6 induced fibrinogen synthesis by hepatocytes, evidenced by a decrease in fibrinogen secretion in the medium and beta chain mRNA expression and to an inhibition of production of the hepatocyte-stimulating activity for fibrinogen biosynthesis (HSF) by LPS-activated monocytes. Noteworthingly, IL-10 induces a significant decrease of the production of OSM by LPS-activated monocytes. In situ activation of monocytes by cytokines in the vessel wall could also contribute to the deposition of fibrin(ogen) derivatives, identified as pathogenic factor.

  1. Elevated D-dimer and fibrinogen levels in serum of preoperative bone fracture patients.

    PubMed

    Liu, Chen; Song, Ying; Zhao, Jingzhong; Xu, Qinzhu; Liu, Ning; Zhao, Lei; Lu, Songsong; Wang, Hui

    2016-01-01

    The changes of coagulation parameters in preoperative fracture patients reflect the coagulation status before surgery. We did retrospective assessment of preoperative fracture patients (n = 113) admitted to the hospital between September 2013 and September 2014. The control group were selected from healthy adults (n = 113) with matched age and gender. Platelet, PT INR, APTT, fibrinogen (FIB) and D-dimer values were collected and analyzed. PT INR level was 1.043 ± 0.119, APTT was 31.91 ± 7.56 s, FIB was 320.6 ± 71.8 mg/dl and D-dimer was 1283 ± 1582 ng/ml for the fracture patients. For the control group, PT INR level was 0.9976 ± 0.0602, APTT was 33.22 ± 2.55 s, FIB was 277.3 ± 44.7 mg/dl and D-dimer was 97.53 ± 63.90 ng/ml. Meanwhile, D-dimer levels of different sites of fractures were also measured: Femora 2448 ± 1961 ng/ml; Humerus 792.4 ± 691.2 ng/ml; Ulna/Radius 619.4 ± 843.7 ng/ml; Vertebra 647.7 ± 787.1 ng/ml; Tibia/Fibula 496.3 ± 268.8 ng/ml; Clavicle 260.9 ± 170.9 ng/ml; Ankle 415.4 ± 286.6 ng/ml. To conclude, D-dimer and fibrinogen levels get higher in preoperative fracture patients than controls. Besides, D-dimer levels are significantly different among different locations of fractures, and our data revealed that D-dimer levels of Femora fracture were higher than other sites.

  2. Role of serum fibrinogen levels in patients with rotator cuff tears.

    PubMed

    Longo, Umile Giuseppe; Petrillo, Stefano; Berton, Alessandra; Spiezia, Filippo; Loppini, Mattia; Maffulli, Nicola; Denaro, Vincenzo

    2014-01-01

    Although rotator cuff (RC) tendinopathy is a frequent pathology of the shoulder, the real understanding of its aetiopathogenesis is still unclear. Several studies showed that RC tendinopathy is more frequent in patients with hyperglycemia, diabetes, obesity, or metabolic syndrome. This paper aims to evaluate the serum concentration of fibrinogen in patients with RC tears. Metabolic disorders have been related to high concentration of serum fibrinogen and the activity of fibrinogen has been proven to be crucial in the development of microvascular damage. Thus, it may produce progression of RC degeneration by reducing the vascular supply of tendons. We report the results of a cross-sectional frequency-matched case-control study comparing the serum concentration of fibrinogen of patients with RC tears with that of a control group of patients without history of RC tears who underwent arthroscopic meniscectomy. We choose to enrol in the control group patients with pathology of the lower limb with a likely mechanic, not metabolic, cause, different from tendon pathology. We found no statistically significant differences in serum concentration of fibrinogen when comparing patients with RC tears and patients who underwent arthroscopic meniscectomy (P = 0.5). Further studies are necessary to clarify the role of fibrinogen in RC disease.

  3. Concentrations of serum amyloid A and plasma fibrinogen in horses undergoing emergency abdominal surgery.

    PubMed

    Daniel, Alexander J; Leise, Britta S; Burgess, Brandy A; Morley, Paul S; Cloninger, Madison; Hassel, Diana M

    2016-05-01

    To compare the perioperative response of serum amyloid A (SAA) to fibrinogen in horses requiring exploratory celiotomy for colic and to determine if SAA could be used to predict complications and outcome. Prospective observational clinical study. University teaching hospital. Eighteen horses undergoing exploratory celiotomy for colic. Inclusion criteria for the study included survival and anesthetic recovery from exploratory celiotomy, no history of surgery within the past year. Blood was obtained via jugular venipuncture before surgery (time 0) and at 24, 48, 72, and 96 hours after recovery from anesthesia. Quantitative and semiquantitative fibrinogen, SAA, total nucleated cell counts, and total protein were evaluated at each time point. Multivariable linear regression was used to assess differences at each time point and after grouping horses according to duration of colic prior to surgery, strangulating surgical lesion or not, presence of systemic inflammatory response syndrome (SIRS) on admission, and postsurgical complications. Significant (P < 0.05) increases in SAA concentrations occurred in all cases after surgery compared to fibrinogen concentration, which only demonstrated a mild, clinically insignificant increase postsurgery. SAA concentrations were also significantly increased (P < 0.05) in cases identified with SIRS prior to surgery and postoperatively at 48 (P = 0.05) and 72 hours (P = 0.02) in horses that developed complications. Measurement of SAA is a more sensitive indicator of inflammation than fibrinogen in the perioperative period of horses requiring exploratory celiotomy for colic. Serial measurement of SAA at 48, 72, and 96 hours after surgery may be helpful to determine risk of complications and guide postoperative management. Measurement of SAA on admission also allows for quantification of SIRS when it is detected clinically. © Veterinary Emergency and Critical Care Society 2015.

  4. National survey of fibrinogen concentrate usage for post-partum hemorrhage in Japan: investigated by the Perinatology Committee, Japan Society of Obstetrics and Gynecology.

    PubMed

    Makino, Shintaro; Takeda, Satoru; Kobayashi, Takao; Murakami, Maki; Kubo, Takahiko; Hata, Toshiyuki; Masuzaki, Hideaki

    2015-08-01

    The aim of this study was to provide basic documents applicable to studying the usefulness of administering fibrinogen concentrate to patients with massive post-partum hemorrhage. We investigated the usage of fibrinogen concentrate at training institutions for specialist physicians of the Japan Society of Obstetrics and Gynecology. The subjects were women who required fibrinogen concentrate for hemostasis of post-partum hemorrhage during the period between April 2008 and March 2013. The underlying diseases, obstetric disseminated intravascular coagulation scores, blood loss, amount of blood transfusion, dose of fibrinogen concentrate administered, and plasma fibrinogen levels before and after the administration of fibrinogen concentrate were retrospectively investigated. Ninety-nine (98.0%) patients survived and two died after taking fibrinogen concentrate. Of the surviving 99 cases, the average amount of blood loss at the time of initial fibrinogen administration and total blood loss was 3559 ± 2103 mL and 4562 ± 3198 mL, respectively. The dose per administration was 3 g, and the plasma fibrinogen level before the initial administration of fibrinogen concentrate was 70.5 mg/dL, thereafter increasing to 187.0 mg/dL. The increase in the fibrinogen level was 32.9 mg/dL/g of fibrinogen concentrate. It was less than 150 mg/dL after the first administration of fibrinogen concentrate only in patients with amniotic fluid embolism and patients with atonic bleeding showed the smallest increase in fibrinogen per gram of fibrinogen concentrate. No adverse events, including thromboembolism, were reported. The results indicated the increase in blood fibrinogen levels to, on occasion, be insufficient even with fibrinogen concentrate use; however, this survey may support the safety and usefulness of fibrinogen concentrate for PPH. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  5. Indications and Risks of Fibrinogen in Surgery and Trauma.

    PubMed

    Spahn, Donat R; Spahn, Gabriela H; Stein, Philipp

    2016-03-01

    Fibrinogen has a central role in coagulation. Following trauma and perioperatively, low fibrinogen levels have been found to be risk factors for exaggerated bleeding, transfusion needs, and adverse outcome. Conversely, treatment with exogenous fibrinogen in critically bleeding patients with low fibrinogen levels has been shown to decrease transfusion needs. Because following trauma and in many perioperative situations fibrinogen is the first coagulation "element" to become critically low, it appears reasonable to target fibrinogen in clinical coagulation algorithms aiming at early specific and goal-directed treatment. A low fibrinogen can be a low plasma concentration or a low functional fibrinogen as assessed by point-of-care techniques such as thromboelastography (TEG) or thromboelastometry (ROTEM). This review summarizes the evidence base for perioperative algorithm-based fibrinogen administration, including the exact thresholds for fibrinogen administration used in the different algorithms. Algorithm-based individualized goal-directed use of fibrinogen resulted in highly significant reduction in transfusion needs, adverse outcomes, in certain studies even mortality, and where investigated reduced costs, with high safety levels at the same time. Best evidence exists in cardiac surgery, followed by trauma, postpartum hemorrhage, and liver transplantation. The introduction of these concepts is highly demanding and requires a tremendous educational effort to familiarize all health care workers with the necessary knowledge and the skills of how to run TEG/ROTEM tests. Future research is needed to compare the efficacy, safety, and costs of different algorithms. This, however, should not prevent us from introducing these expedient point-of-care-based algorithms clinically today.

  6. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    SciTech Connect

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  7. Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders.

    PubMed

    Neerman-Arbez, Marguerite; de Moerloose, Philippe; Casini, Alessandro

    2016-06-01

    Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Congenital fibrinogen deficiency

    MedlinePlus

    ... brain (very rare) Bleeding in the joints Heavy bleeding after injury or surgery Nosebleeds that do not stop easily People with a reduced level of fibrinogen bleed less often and the bleeding is not as severe. Those with a problem ...

  9. Surface modification with poly(sulfobetaine methacrylate-co-acrylic acid) to reduce fibrinogen adsorption, platelet adhesion, and plasma coagulation.

    PubMed

    Kuo, Wei-Hsuan; Wang, Meng-Jiy; Chien, Hsiu-Wen; Wei, Ta-Chin; Lee, Chiapyng; Tsai, Wei-Bor

    2011-12-12

    Zwitterionic sulfobetaine methacrylate (SBMA) polymers were known to possess excellent antifouling properties due to high hydration capacity and neutral charge surface. In this study, copolymers of SBMA and acrylic acid (AA) with a variety of compositions were synthesized and were immobilized onto polymeric substrates with layer-by-layer polyelectrolyte films via electrostatic interaction. The amounts of platelet adhesion and fibrinogen adsorption were determined to evaluate hemocompatibility of poly(SBMA-co-AA)-modified substrates. Among various deposition conditions by modulating SBMA ratio in the copolymers and pH of the deposition solution, poly(SBMA(56)-co-AA(44)) deposited at pH 3.0 possessed the best hemocompatibility. This work demonstrated that poly(SBMA-co-AA) copolymers adsorbed on polyelectrolyte-base films via electrostatic interaction improve hemocompatibility effectively and are applicable for various substrates including TCPS, PU, and PDMS. Furthermore, poly(SBMA-co-AA)-coated substrate possesses great durability under rigorous conditions. The preliminary hemocompatibility tests regarding platelet adhesion, fibrinogen adsorption, and plasma coagulation suggest the potential of this technique for the application to blood-contacting biomedical devices.

  10. Social connectedness is associated with fibrinogen level in a human social network.

    PubMed

    Kim, David A; Benjamin, Emelia J; Fowler, James H; Christakis, Nicholas A

    2016-08-31

    Socially isolated individuals face elevated rates of illness and death. Conventional measures of social connectedness reflect an individual's perceived network and can be subject to bias and variation in reporting. In this study of a large human social network, we find that greater indegree, a sociocentric measure of friendship and familial ties identified by a subject's social connections rather than by the subject, predicts significantly lower concentrations of fibrinogen (a biomarker of inflammation and cardiac risk), after adjusting for demographics, education, medical history and known predictors of cardiac risk. The association between fibrinogen and social isolation, as measured by low indegree, is comparable to the effect of smoking, and greater than that of low education, a conventional measure of socioeconomic disadvantage. By contrast, outdegree, which reflects an individual's perceived connectedness, displays a significantly weaker association with fibrinogen concentrations.

  11. Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe)

    PubMed Central

    Wassel, Christina L.; Lange, Leslie A.; Keating, Brendan J.; Taylor, Kira C.; Johnson, Andrew D.; Palmer, Cameron; Ho, Lindsey A.; Smith, Nicholas L.; Lange, Ethan M.; Li, Yun; Yang, Qiong; Delaney, Joseph A.; Tang, Weihong; Tofler, Geoffrey; Redline, Susan; Taylor, Herman A.; Wilson, James G.; Tracy, Russell P.; Jacobs, David R.; Folsom, Aaron R.; Green, David; O'Donnell, Christopher J.

    2011-01-01

    Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23 634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47 539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk. PMID:20978265

  12. Rhodococcus equi pneumonia in foals: an assessment of the early diagnostic value of serum amyloid A and plasma fibrinogen concentrations in equine clinical practice.

    PubMed

    Passamonti, F; Vardi, D M; Stefanetti, V; Marenzoni, M L; Prato, S; Cévese, P; Coletti, M; Pepe, M; Casagrande Proietti, P; Olea-Popelka, F

    2015-02-01

    Early diagnosis and prevention of Rhodococcus equi pneumonia in foals represent important goals for equine clinicians. Recent protocols for diagnosis and treatment of Rhodococcosis in foals typically rely on a multimodal approach based on sonographic evidence suggestive of pyogranulomas, sonographic abscess scores and laboratory findings including plasma fibrinogen concentrations, blood biochemistry testing and platelet and leukocyte counts. The aim of this study was to assess the utility of weekly testing of serum amyloid A (SAA) and plasma fibrinogen concentrations in foals to achieve early diagnosis of R. equi pneumonia prior to the onset of clinical signs. This testing was used to simulate a clinically practical screening procedure and compared with thoracic ultrasonography performed in parallel. The present study suggests that SAA does not represent a reliable early marker of Rhodococcosis when plasma concentrations are tested weekly. However, when clinical signs of R. equi pneumonia are present, SAA concentrations may allow clinicians to obtain 'real-time' indications concerning both the progress of infection and the effectiveness of therapy. This study raises the possibility that plasma fibrinogen monitoring starting at 1 week of age and repeated on a weekly basis, could serve as a screening test allowing clinicians to identify foals as suspected of R. equi infection. Future investigations regarding both physiological plasma fibrinogen concentrations in foals as well as fibrinogen kinetics in foals affected with R. equi pneumonia, including the establishment of appropriate reference intervals for the test method employed in this study, will be necessary in order to clarify this possibility. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Fibrinogen Test

    MedlinePlus

    ... also been associated with coronary heart disease , myocardial infarction , and peripheral arterial disease. In some cases, fibrinogen ... with: Acute infections Cancer Coronary heart disease , myocardial infarction Stroke Inflammatory disorders (like rheumatoid arthritis and glomerulonephritis , ...

  14. Rapid measurement of fibrinogen concentration in whole blood using a steel ball coagulometer

    PubMed Central

    Schlimp, Christoph J.; Khadem, Anna; Klotz, Anton; Solomon, Cristina; Hochleitner, Gerald; Ponschab, Martin; Redl, Heinz; Schöchl, Herbert

    2015-01-01

    BACKGROUND Fibrinogen plays a key role in hemostasis and is the first coagulation factor to reach critical levels in bleeding patients. Current European guidelines on the management of traumatic or perioperative bleeding recommend fibrinogen supplementation at specific threshold levels. Whole blood viscoelastic tests provide fast evaluation of fibrin deficits. Fast measurement of plasma fibrinogen concentration is not yet available. We investigated a method to rapidly determine whole blood fibrinogen concentration using standard Clauss assays and a steel ball coagulometer and provide an estimate of the “plasma-equivalent” fibrinogen concentration within minutes by adjustment of the measured whole blood fibrinogen concentration with a quickly measureable hemoglobin-derived hematocrit. METHODS The feasibility of this approach was tested with a Clauss assay using multiple porcine fresh blood samples obtained during in vivo bleeding, hemodilution, and after treatment with hemostatic therapy. Two different Clauss assays were then tested using multiple human volunteers’ blood samples diluted in vitro and supplemented with fibrinogen concentrate. Comparative measurements with fibrin-based thromboelastometry tests were performed. RESULTS Regression and Bland-Altman analyses of derived “plasma-equivalent” fibrinogen and measured plasma fibrinogen concentration was excellent in porcine and human blood samples, especially in the ranges relevant to traumatic or perioperative bleeding. CONCLUSION Fast whole blood fibrinogen measurements could be considered as an alternative to plasma fibrinogen measurement for acute bleeding management in trauma and perioperative care settings. Further studies are needed to prove this concept and determine the turnaround times for its clinical application in emergency departments and operating theaters. PMID:25742256

  15. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

    PubMed Central

    2011-01-01

    Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment. PMID:22029888

  16. No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

    PubMed Central

    Chu, Audrey Y.; Trompet, Stella; Lopez, Lorna M.; Fornage, Myriam; Teumer, Alexander; Tang, Weihong; Rudnicka, Alicja R.; Mälarstig, Anders; Hottenga, Jouke-Jan; Kavousi, Maryam; Lahti, Jari; Tanaka, Toshiko; Hayward, Caroline; Huffman, Jennifer E.; Morange, Pierre-Emmanuel; Rose, Lynda M.; Basu, Saonli; Rumley, Ann; Stott, David J.; Buckley, Brendan M.; de Craen, Anton J. M.; Sanna, Serena; Masala, Marco; Biffar, Reiner; Homuth, Georg; Silveira, Angela; Sennblad, Bengt; Goel, Anuj; Watkins, Hugh; Müller-Nurasyid, Martina; Rückerl, Regina; Taylor, Kent; Chen, Ming-Huei; de Geus, Eco J. C.; Hofman, Albert; Witteman, Jacqueline C. M.; de Maat, Moniek P. M.; Palotie, Aarno; Davies, Gail; Siscovick, David S.; Kolcic, Ivana; Wild, Sarah H.; Song, Jaejoon; McArdle, Wendy L.; Ford, Ian; Sattar, Naveed; Schlessinger, David; Grotevendt, Anne; Franzosi, Maria Grazia; Illig, Thomas; Waldenberger, Melanie; Lumley, Thomas; Tofler, Geoffrey H.; Willemsen, Gonneke; Uitterlinden, André G.; Rivadeneira, Fernando; Räikkönen, Katri; Chasman, Daniel I.; Folsom, Aaron R.; Lowe, Gordon D.; Westendorp, Rudi G. J.; Slagboom, P. Eline; Cucca, Francesco; Wallaschofski, Henri; Strawbridge, Rona J.; Seedorf, Udo; Koenig, Wolfgang; Bis, Joshua C.; Mukamal, Kenneth J.; van Dongen, Jenny; Widen, Elisabeth; Franco, Oscar H.; Starr, John M.; Liu, Kiang; Ferrucci, Luigi; Polasek, Ozren; Wilson, James F.; Oudot-Mellakh, Tiphaine; Campbell, Harry; Navarro, Pau; Bandinelli, Stefania; Eriksson, Johan; Boomsma, Dorret I.; Dehghan, Abbas; Clarke, Robert; Hamsten, Anders; Boerwinkle, Eric; Jukema, J. Wouter; Naitza, Silvia; Ridker, Paul M.; Völzke, Henry; Deary, Ian J.; Reiner, Alexander P.; Trégouët, David-Alexandre; O'Donnell, Christopher J.; Strachan, David P.; Peters, Annette; Smith, Nicholas L.

    2014-01-01

    Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10−8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations. PMID:25551457

  17. Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

    PubMed

    Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

    2016-01-01

    Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

  18. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded guar sulfate].

    PubMed

    Zhu, Ye; Fang, Bo; Huang, Li; Guan, Chen; Yang, Guang

    2008-10-01

    Degraded guar was prepared by acid with guar as the main material, which was then brought into reaction with chlorosulfonic acid under proper conditions, the sulfonated degraded guar was obtained successfully. The effects of sulfonation conditions on the SO4(2-) content were investigated, and the proper reaction conditions were determined. The results of infrared spectrometry showed that this sulfated derivative is a novel heparin-like polysaccharide. At the same time, the selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded guar gum sulfate was studied. The experimental results showed that degraded guar gum sulfate is a novel LDL/ Fib purifying agent. When pH= 5.15 and the initial concentration of the degraded guar gum sulfate is 2500 mg/L, the reduction percentages were about 60%-66% for total cholesterol, about 76%-89% for LDL and very low-density lipoproteins (VLDL), and almost 100% for fibrinogen. There were no significant changes regarding the level of high-density lipoproteins and total proteins.

  19. Haem-assisted dityrosine-cross-linking of fibrinogen under non-thermal plasma exposure: one important mechanism of facilitated blood coagulation

    PubMed Central

    Ke, Zhigang; Huang, Qing

    2016-01-01

    Although blood coagulation facilitated by non-thermal plasma has been reported several years ago, the insight to the involved mechanisms is still rather limited. In this work, we report our discovery of a new mechanism for the haem-promoted blood-coagulation caused by non-thermal plasma treatment. The reason for the haem role is due to that its oxidized form, namely, hematin, can promote the dityrosine cross-linking of fibrinogen, the most important coagulation protein, to form a membrane-like layer on the surface of the treated blood with plasma exposure. Both haem and non-thermal-plasma generated hydrogen peroxide are requisite for the cross-linking process. We confirmed that fibrinogen can coordinate with the haem iron to form a protein-haem complex which shows pseudo-peroxidase activity, and in the presence of hydrogen peroxide, the complex can induce the dityrosine formation between fibrinogen molecules, leading to the fibrin network necessary for the blood coagulation. Understanding of such an underlying mechanism can be useful to guide more efficient application of non-thermal plasma in the management of hemostasis, thrombosis and etc. PMID:27229173

  20. Interaction of human plasma fibrinogen with commercially pure titanium as studied with atomic force microscopy and X-ray photoelectron spectroscopy.

    PubMed

    Keere, Isabel Van De; Willaert, Ronnie; Hubin, Annick; Vereecken, Jean

    2008-03-04

    The surface of a biomaterial interacts with the body fluid upon implantation in the human body. The biocompatibility of a material is strongly influenced by the adsorption of proteins onto the surface. Titanium is frequently used as a biomaterial for implants in orthopedics and cardiovascular devices. Understanding the biocompatibility is very important to improve implants. The surface chemistry of an implant material and its influence on the interaction with body fluid is crucial in that perspective. The main goal of this study was to investigate the conformation of human plasma fibrinogen (HPF) adsorbed on commercially pure titanium (CP Ti) on a molecular level by means of ex situ atomic force microscopy (AFM). With X-ray photoelectron spectroscopy combined with argon ion beam depth profiling, it was shown that the oxide layer present at the surface was mainly composed of TiO2, with a small percentage of Ti2O3. Ex situ AFM imaging showed the conformation of HPF on CP Ti. Single molecules and aggregates of fibrinogen were observed. The trinodular structure of single HPF molecules (two spherical D domains at the distal ends of the extended molecule and the central spherical E domain) adsorbed onto CP Ti was visualized. Aggregate formation through the connection of the D domains of the HPF molecules was observed on CP Ti. The alphaC domains of HPF were not visible on CP Ti. The ex situ AFM images indicated conformational changes of HPF upon adsorption onto CP Ti. The conformation of the adsorbed HPF molecules was different on mica and titanium. The difference in wettability between both substrates caused a larger spread of the protein on the CP Ti surface and thus resulted in a larger perturbation to the native structure of HPF as compared to mica.

  1. The role of complement C3 and fibrinogen in monocyte adhesion to PEO like plasma deposited tetraglyme

    PubMed Central

    Szott, Luisa M.; Horbett, Thomas A.

    2010-01-01

    The role of complement C3 in mediating adhesion of monocytes to plasma deposited tetraglyme surfaces was studied. Although fibrinogen (Fg) is usually considered the main factor in mediating phagocyte attachment, plasma deposited PEO-like tetraethylene glycol dimethyl ether (tetraglyme) coatings that have ultra-low Fg adsorption (< 10 ng/cm2) from low concentration solutions and low monocyte adhesion in vitro still show high phagocyte adhesion after short implantations and later become encapsulated when tested in vivo. To test whether higher Fg adsorption under in vivo conditions could explain the higher in vivo reactivity, we again measured the resistance of tetraglyme films to Fg adsorption. We found a surprising and previously unreported increased amount of adsorbed Fg on tetraglyme surfaces from higher concentration protein solutions. However, monocyte adhesion to tetraglyme did not markedly increase despite the increased Fg adsorption. We thus suspected proteins other than Fg must be responsible for the increased in vivo reactivity. We found that on tetraglyme pre-adsorbed with C3-depleted serum, monocyte adhesion was greatly reduced as compared to samples adsorbed with normal serum. Addition of exogenous pure C3 to the serum used to pre-adsorb the surfaces restored monocyte adhesion to tetraglyme coatings. While Fg clearly plays an important role in mediating monocyte adhesion to tetraglyme surfaces, the results show an additional role for adsorbed C3 in monocyte adhesion. PMID:20939050

  2. Comparison of a new automated kinetically determined fibrinogen assay with the 3 most used fibrinogen assays (functional, derived and nephelometric) in Austrian laboratories in several clinical populations and healthy controls.

    PubMed

    Halbmayer, W M; Haushofer, A; Schön, R; Radek, J; Fischer, M

    1995-01-01

    A new automated kinetically determined fibrinogen assay was measured in plasmas of healthy subjects and three clinical cohorts (acute-phase reaction, liver cirrhosis and fibrinolytic therapy) that were expected to show normal, high and low levels of fibrinogen. The results were compared with the results of fibrinogen measurement using the derived method, the method according to Clauss and an immunological-nephelometric method. Altogether, the best correlation was achieved between the kinetic and the derived method. However, results from the derived method were generally higher than values obtained through the kinetic method. This was particularly true for high concentration levels above 400 mg/dl (patients with acute phase reaction) as well as for plasmas containing fibrin(ogen) degradation products and low concentrations of fibrinogen (below 150 mg/dl). Fibrinogen determinations in several commercial plasma pools with declared fibrinogen levels show remarkable heterogeneity when different methods were applied. To improve the discernment of fibrinogen determinations we suggest adjustment of standard preparations to international reference materials and the specification of the method used. Furthermore the attending physician is asked to cast a critical eye on fibrinogen values with regard to the used method of determination.

  3. [Relation of socioeconomic levels and life style to fibrinogen and von Willebrand factor in healthy Venezuelans and those with ischemic cardiopathy].

    PubMed

    Rodríguez-Larralde, Alvaro; Mijares, Mercedes E; Nagy, Elena; Espinosa, Raul; Ryder, Elena; Diez-Ewald, María P; Torres, Enrique; Coll-Sangrona, Enriqueta; Rodríguez-Roa, Elsy; Carvajal, Zoila; Lundberg, Ulf; Campos, Gilberto; Gill, Amparo; Arocha-Piñango, Carmen L

    2005-06-01

    Previous studies in Europe, U.S.A and Japan have revealed an inverse relationship between socioeconomic levels and fibrinogen concentration. Similar results have been reported in a smaller number of studies for concentrations of von Willebrand factor. In this opportunity we present results on the relationship between smoking, drinking, physical activity, age and socioeconomic level on fibrinogen and von Willebrand factor concentrations in a Venezuelan sample. The control population consisted of 978 men and 968 women. Patients with coronary heart disease were 172 males and 78 females. The presence of one or more of the following conditions: smoking or less than 5 years of having quit, non drinkers or drinking in excess, and a reduced physical activity, was considered a health related risk factor for high levels of these two haemostatic variables. Our results indicate that in Controls, the socioeconomic level had a significant effect on fibrinogen and von Willebrand factor levels, only in women: those of lower socioeconomic levels had the highest concentrations. This difference was maintained when age was taken into account. Health related behaviors had no significant effect on either variable. In patients, age had no effect on either variable. The health behavior risk factor had a significant effect only on fibrinogen of male patients, and socioeconomic level had a significant effect only on the fibrinogen of female patients. More studies in Venezuela are recommended, in order to increase our knowledge on the relationship between socioeconomic levels, haemostatic markers and the occurrence of coronary heart disease.

  4. Direct detection of fibrinogen in human plasma using electric-double-layer gated AlGaN/GaN high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Regmi, Abiral; Sarangadharan, Indu; Chen, Yen-Wen; Hsu, Chen-Pin; Lee, Geng-Yen; Chyi, Jen-Inn; Shiesh, Shu-Chu; Lee, Gwo-Bin; Wang, Yu-Lin

    2017-08-01

    Fibrinogen found in blood plasma is an important protein biomarker for potentially fatal diseases such as cardiovascular diseases. This study focuses on the development of an assay to detect plasmatic fibrinogen using electrical double layer gated AlGaN/GaN high electron mobility transistor biosensors without complex sample pre-treatment methods used in the traditional assays. The test results in buffer solution and clinical plasma samples show high sensitivity, specificity, and dynamic range. The sensor exhibits an ultra-low detection limit of 0.5 g/l and a detection range of 0.5-4.5 g/l in 1× PBS with 1% BSA. The concentration dependent sensor signal in human serum samples demonstrates the specificity to fibrinogen in a highly dense matrix of background proteins. The sensor does not require complicated automation, and quantitative results are obtained in 5 min with <5 μl sample volume. This sensing technique is ideal for speedy blood based diagnostics such as POC (point of care) tests, homecare tests, or personalized healthcare.

  5. Development of a fibrinogen-specific sandwich enzyme-linked immunosorbent assay microarray assay for distinguishing between blood plasma and serum samples.

    PubMed

    Gonzalez, Rachel M; Zhang, Qibin; Zangar, Richard C; Smith, Richard D; Metz, Thomas O

    2011-07-01

    We have developed a fibrinogen-specific sandwich enzyme-linked immunosorbent assay (ELISA) microarray assay for use in qualitatively distinguishing between blood plasma and serum samples. Three capture antibodies (49D2, HPA001900, and F8512) were evaluated in conjunction with 1D6 as the detection antibody. The data show that 49D2 and (to a lesser extent) F8512 successfully identify previously unknown plasma and serum samples based on approximately a 28-fold difference in signal intensity between the sample types. This assay has utility in rapidly identifying previously archived clinical samples with incomplete annotation in a high-throughput manner prior to proteomic analyses.

  6. Development of a Fibrinogen-Specific Sandwich Enzyme-Linked Immunosorbent Assay Microarray Assay for Distinguishing Between Blood Plasma and Serum Samples

    SciTech Connect

    Gonzales, Rachel M.; Zhang, Qibin; Zangar, Richard C.; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    We have developed a fibrinogen-specific sandwich ELISA microarray assay for use in qualitatively distinguishing between blood plasma and serum samples. Three capture antibodies, 49D2, HPA001900, and F8512, were evaluated in conjunction with 1D6 as detection antibody, and the data show that 49D2 and, to a lesser extent, F8512 successfully identify previously unknown plasma and serum samples based upon a ~28-fold difference in signal intensity between the sample types. This assay has utility in rapidly identifying previously archived clinical samples with incomplete annotation in a high throughput manner prior to proteomics analyses.

  7. A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia.

    PubMed

    Zhang, Jian; Zhao, Xiaojuan; Wang, Zhaoyue; Yu, Ziqiang; Cao, Lijuan; Zhang, Wei; Bai, Xia; Ruan, Changgeng

    2013-07-01

    Congenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.

  8. Quantitative assessment of fibrinogen cross-linking by epsilon aminocaproic acid in patients with end-stage liver disease.

    PubMed

    Quach, Thien; Tippens, Melissa; Szlam, Fania; Van Dyke, Rebecca; Levy, Jerrold H; Csete, Marie

    2004-01-01

    Analysis of the effectiveness of antifibrinolytic therapy for liver transplant recipients is hampered by lack of quantitative assays for assessing drug effects. We adapted chemical engineering tools used in polymerization studies to quantify fibrinogen cross-linking by plasma from liver transplant patients obtained before and after epsilon aminocaproic acid (EACA) therapy. A target fluorescein isothiocyanate-fibrinogen (FITC-fibrinogen) molecule was constructed; it fluoresces in a quantifiable pattern when in solution, and undergoes cross-linking in the presence of plasmin inhibitors. Cross-linking quenches the fluorescent signal, and the quenching is a quantifiable endpoint. Thus fluorescence from this reporter molecule can be used to assess functional improvement in fibrinogen cross-linking as a result of antifibrinolytic therapies, and it is sensitive to picomolar amounts of plasmin inhibitors and activators. Cross-linking of FITC-fibrinogen by patient plasma, before and after EACA therapy, was assessed using fluorescence spectrometry. Fluorescence patterns from FITC-fibrinogen indicated no significant cross-linking of the target fibrinogen as a consequence of EACA in posttreatment plasma. When the fibrinogen-FITC target was assayed without plasma in the presence of EACA at concentrations that bracket therapeutic levels (100 and 400 microg/ml), significant fluorescence quenching (target FITC-fibrinogen cross-linking) was achieved. These results suggest that fibrinogen-FITC fluorescence is sensitive enough to detect EACA activity in clinically relevant ranges, but that EACA given in usual doses is insufficient to promote fibrinogen cross-linking in patients with end-stage liver disease.

  9. Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His

    PubMed Central

    Luo, Meiling; Deng, Donghong; Xiang, Liqun; Cheng, Peng; Liao, Lin; Deng, Xuelian; Yan, Jie; Lin, Faquan

    2016-01-01

    Abstract Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees. Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS–PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM). The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS–PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal. Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen. PMID

  10. Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His.

    PubMed

    Luo, Meiling; Deng, Donghong; Xiang, Liqun; Cheng, Peng; Liao, Lin; Deng, Xuelian; Yan, Jie; Lin, Faquan

    2016-09-01

    Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS-PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen.

  11. The association between fibrinogen reactivity to mental stress and high-sensitivity cardiac troponin T in healthy adults.

    PubMed

    Lazzarino, Antonio Ivan; Hamer, Mark; Gaze, David; Collinson, Paul; Rumley, Ann; Lowe, Gordon; Steptoe, Andrew

    2015-09-01

    Plasma fibrinogen is considered as a positive mediator between mental stress and cardiovascular disease because it is an acute-phase protein released in response to mental stress and a coagulation factor. However those three factors have never been studied together within a single integrated framework, using cardiac troponin T as a marker of cardiovascular risk. 491 disease-free men and women aged 53-76 were tested for fibrinogen levels before, immediately after, and following recovery from standardized mental stress tasks. We measured plasma cardiac troponin T using a high-sensitivity assay (HS-CTnT) and coronary calcification using electron-beam dual-source computed tomography. The average fibrinogen concentration increased by 5.1% (s.d.=7.3) in response to stress and then tended to return to baseline values. People with higher baseline fibrinogen values had smaller increases (blunted responses) following the stress task (P=0.001), and people with higher stress responses showed better recovery (P<0.001). In unadjusted analyses, higher baseline fibrinogen was associated with higher chances of having detectable HS-CTnT (P=0.072) but, conversely, higher fibrinogen response was associated with lower chances of having detectable HS-CTnT (P=0.007). The adjustment for clinical, inflammatory, and haemostatic factors, as well as for coronary calcification eliminated the effect of baseline fibrinogen, whereas the negative association between fibrinogen response and HS-CTnT remained robust: the odds of detectable HS-CTnT halved for each 10% increase in fibrinogen concentration due to stress (OR=0.49, P=0.007, 95% CI=0.30-0.82). Greater fibrinogen responses to mental stress are associated with lower likelihood of detectable high-sensitivity troponin T plasma concentration. A more dynamic fibrinogen response appears to be advantageous for cardiovascular health. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency.

    PubMed

    Asselta, Rosanna; Platè, Manuela; Robusto, Michela; Borhany, Munira; Guella, Ilaria; Soldà, Giulia; Afrasiabi, Abdolreza; Menegatti, Marzia; Shamsi, Tahir; Peyvandi, Flora; Duga, Stefano

    2015-03-01

    Fibrinogen is a plasma glycoprotein mainly synthesised by hepatocytes and circulating as a 340-kDa hexamer consisting of two sets of three different polypeptide chains (Aα, Bβ, and γ, encoded by the FGA, FGB, and FGG gene, respectively). Congenital afibrinogenaemia and hypofibrinogenaemia are rare bleeding disorders characterised by abnormally low levels of functional and immunoreactive fibrinogen in plasma, associated with haemorrhagic manifestations of variable severity. While afibrinogenaemia is caused by mutations in the homozygous or compound heterozygous state in one of the three fibrinogen genes, hypofibrinogenaemia is generally due to heterozygous mutations, and is usually characterised by a milder phenotype. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination codons, and missense mutations often affecting fibrinogen assembly and/or secretion. Here we report the clinical and molecular characterisation of 13 unrelated afibrinogenaemic and eight hypofibrinogenaemic patients, leading to the identification of 17 different mutations (10 hitherto unknown). All the newly-identified missense and splicing mutations werein vitro expressed to verify their pathogenic role. Our data increase the number of mutations causing quantitative fibrinogen deficiencies by about 7 %. The high number of private mutations identified in the analysed probands indicates that the full mutational screening of the three fibrinogen genes is still required for molecular diagnosis.

  13. Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease. Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium.

    PubMed

    Miller, Bruce E; Tal-Singer, Ruth; Rennard, Stephen I; Furtwaengler, Armin; Leidy, Nancy; Lowings, Michael; Martin, Ubaldo J; Martin, Thomas R; Merrill, Debora D; Snyder, Jeffrey; Walsh, John; Mannino, David M

    2016-03-15

    The COPD Foundation Biomarker Qualification Consortium (CBQC) is a unique public-private partnership established in 2010 between the COPD Foundation, the pharmaceutical industry, and academic chronic obstructive pulmonary disease (COPD) experts with advisors from the U.S. NHLBI and the Food and Drug Administration (FDA). This was a direct response to the 2009 publication of a guidance on qualification of drug development tools by the FDA. Although data were believed to be available from publicly funded and industry-funded studies that could support qualification of several tools, the necessary data resided in disparate databases. The initial intent of the CBQC was to integrate these data and submit a dossier for the qualification. This led to the FDA qualification of plasma fibrinogen as a prognostic or enrichment biomarker for all-cause mortality and COPD exacerbations in July 2015. It is the first biomarker drug development tool qualified for use in COPD under the FDA's drug development tool qualification program. This perspective summarizes the FDA's qualification process, the formation of the CBQC, and the effort that led to a successful outcome for plasma fibrinogen and discusses implications for future biomarker qualification efforts.

  14. Tracer diffusion inside fibrinogen layers

    NASA Astrophysics Data System (ADS)

    Cieśla, Michał; Gudowska-Nowak, Ewa; Sagués, Francesc; Sokolov, Igor M.

    2014-01-01

    We investigate the obstructed motion of tracer (test) particles in crowded environments by carrying simulations of two-dimensional Gaussian random walk in model fibrinogen monolayers of different orientational ordering. The fibrinogen molecules are significantly anisotropic and therefore they can form structures where orientational ordering, similar to the one observed in nematic liquid crystals, appears. The work focuses on the dependence between level of the orientational order (degree of environmental crowding) of fibrinogen molecules inside a layer and non-Fickian character of the diffusion process of spherical tracer particles moving within the domain. It is shown that in general particles motion is subdiffusive and strongly anisotropic, and its characteristic features significantly change with the orientational order parameter, concentration of fibrinogens, and radius of a diffusing probe.

  15. Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study.

    PubMed Central

    Friedlander, Y; Elkana, Y; Sinnreich, R; Kark, J D

    1995-01-01

    Genetic and environmental determinants of plasma fibrinogen were investigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first adjusted for variability in sex and age. There was a significant familial aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Commingling analysis implied that in this population a mixture of two normal distributions fit the adjusted fibrinogen levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex- and age-adjusted data. Heterogeneous etiologies for individual differences were suggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of distributions. In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be rejected. However, when the regression model for sex and age allowed coefficients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results suggested that particular ousiotypes determined by the major environmental factor are associated with a steeper increase of fibrinogen with age. While at the age of 20 years, the major environmental factor contributed 10% to fibrinogen variability, and 48% was explained by polygenic loci, at 80 years of age, the major factor explained 64% and only approximately 20% was explained by polygenic factors. PMID:7726177

  16. The role of fibrinogen: a new paradigm in the treatment of coagulopathic bleeding.

    PubMed

    Sørensen, Benny; Tang, Mariann; Larsen, Ole H; Laursen, Peter N; Fenger-Eriksen, Christian; Rea, Catherine J

    2011-01-01

    Fibrinogen is involved in both primary and secondary hemostasis, playing an important role in platelet aggregation and the establishment of a fibrin network. Recent evidence suggests that very high levels of fibrinogen act as antithrombin and can reduce endogenous thrombin potential and compromise clot stability, particularly following a low tissue factor stimulus. Several laboratory methods for measuring plasma fibrinogen concentrations are available, but results vary depending on the type of method and the use of artificial colloid plasma expanders. Adopting only the Clauss method can provide erroneously high levels when used in patients who have received colloid plasma expanders. This may contribute to a hazardous delay or complete lack of treatment. Multiple in vitro experiments, animal studies, and proof-of-principle randomized, clinical studies have recently suggested that hemostatic intervention with a fibrinogen concentrate may be efficient and safe in controling perioperative bleeding. In particular, fibrinogen concentrate has a key role in improving clotting function and reducing blood loss in settings such as trauma and cardiothoracic surgery. However, prospective studies are needed to determine the clinical efficacy and safety of fibrinogen concentrate when used as a hemostatic intervention for patients with massive bleeding due to trauma or surgery.

  17. Epidemiology and treatment of congenital fibrinogen deficiency.

    PubMed

    Peyvandi, Flora

    2012-12-01

    Congenital fibrinogen deficiency is a rare bleeding disorder, affecting either the quantity (afibrinogenemia, hypofibrinogenemia) or quality (dysfibrinogenemia) of circulating fibrinogen. There is a strong association between fibrinogen activity levels and clinical bleeding severity. Patients with afibrinogenemia experience frequent, often severe, spontaneous bleeds into the muscles and joints and are at significant risk of intracranial hemorrhage. Patients with hypofibrinogenemia are usually asymptomatic; however, they are vulnerable to bleeding after trauma. Dysfibrinogenemia is associated with both spontaneous bleeding and a relatively high risk of thrombosis. Fibrinogen replacement therapy is effective in treating bleeding episodes in congenital fibrinogen deficiency. Fibrinogen concentrates are the preferred treatment option and guidelines now exist for their on-demand use and to manage surgery. Prophylaxis may benefit patients with afibrinogenemia and others with a severe bleeding tendency. The dose and frequency of administration should be adjusted to maintain a fibrinogen activity level >0.5-1.0 g/L. Pregnant women with afibrinogenemia require prophylactic factor replacement as early as possible during pregnancy, continuing throughout pregnancy, and after the birth. Fibrinogen replacement should also be considered in pregnant women with other fibrinogen deficiencies. The risk of thrombosis presents an additional management challenge in these patients, often necessitating the concurrent use of anticoagulants and fibrinogen. Although basic guidelines have been developed, further studies are needed to help optimize treatment in different patient groups under different clinical circumstances and to improve our understanding of thrombotic events. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Hydrodynamic characterization of recombinant human fibrinogen species

    PubMed Central

    Raynal, Bertrand; Cardinali, Barbara; Grimbergen, Jos; Profumo, Aldo; Lord, Susan T.; England, Patrick; Rocco, Mattia

    2013-01-01

    Introduction Fibrinogen is a key component of the blood coagulation system and plays important, diverse roles in several relevant pathologies such as thrombosis, hemorrhage, and cancer. It is a large glycoprotein whose three-dimensional molecular structure is not fully known. Furthermore, circulating fibrinogen is highly heterogeneous, mainly due to proteolytic degradation and alternative mRNA processing. Recombinant production of human fibrinogen allows investigating the impact on the three-dimensional structure of specific changes in the primary structure. Methods We performed analytical ultracentrifugation analyses of a full-length recombinant human fibrinogen, its counterpart purified from human plasma, and a recombinant human fibrinogen with both Aα chains truncated at amino acid 251, thus missing their last 359 amino acid residues. Results We have accurately determined the translational diffusion and sedimentation coefficients (Dt(20,w)0, s(20,w)0) of all three species. This was confirmed by derived molecular weights within 1% for the full length species, and 5% for the truncated species, as assessed by comparison with SDS-PAGE/Western blot analyses and primary structure data. No significant differences in the values of Dt(20,w)0 and s(20,w)0 were found between the recombinant and purified full length human fibrinogens, while slightly lower and higher values, respectively, resulted for the recombinant truncated human fibrinogen compared to a previously characterized purified human fibrinogen fragment X obtained by plasmin digestion. Conclusions Full-length recombinant fibrinogen is less polydisperse but hydrodynamically indistinguishable from its counterpart purified from human plasma. Recombinant Aα251-truncated human fibrinogen instead behaves differently from fragment X, suggesting a role for the Bβ residues 1–52 in inter-molecular interactions. Overall, these new hydrodynamic data will constitute a reliable benchmark against which models of

  19. Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study.

    PubMed

    Carty, Cara L; Cushman, Mary; Jones, Daniel; Lange, Leslie A; Hindorff, Lucia A; Rice, Kenneth; Jenny, Nancy S; Durda, J Peter; Walston, Jeremy; Carlson, Christopher S; Nickerson, Debbie; Tracy, Russell P; Reiner, Alex P

    2008-02-01

    Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European- (EA) and African-descent (AA) adults (> or = 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807, FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437; each additional copy of the minor allele was associated with 13 mg/dl (95%CI: 9-16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR = 1.9 (95%CI: 1.3-2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.

  20. Experimental hepatic necrosis: Studies on coagulation abnormalities, plasma clearance, and organ distribution of 125I-labelled fibrinogen

    PubMed Central

    Rake, M. O.; Flute, P. T.; Pannell, G.; Shilkin, K. B.; Williams, Roger

    1973-01-01

    Studies in the rat with hepatic necrosis induced by carbon tetrachloride showed that the abnormalities in one-stage coagulation tests and the increased catabolism of fibrinogen were similar to those found in man with acute viral or drug-induced hepatic necrosis. Determination of the distribution of the radioactive label shows that excessive deposition was maximal in the liver but also occurred in the spleen. The appearance is delayed by heparin but accelerated by tranexamic acid. ImagesFig 1Fig 2 PMID:4729927

  1. Relationship between factor XIII activity, fibrinogen, haemostasis screening tests and postoperative bleeding in cardiopulmonary bypass surgery.

    PubMed

    Blome, Markus; Isgro, Frank; Kiessling, Arndt Holger; Skuras, Jan; Haubelt, Hannelore; Hellstern, Peter; Saggau, Werner

    2005-06-01

    We investigated the relationship between factor XIII, fibrinogen, blood coagulation screening tests and postoperative bleeding in 98 patients undergoing cardiopulmonary bypass (CPB) surgery. All patients received aprotinin. Blood samples were collected preoperatively (T1),after termination of CPB (T2),12 h (T3) and 24 h (T4) after surgery to determine FXIII activity, fibrinogen, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimers (DD). Laboratory results were correlated with the chest tube drainage 24 h after surgery and compared between patients with 24-hour chest tube drain volumes in the lower (Group 1) with those in the upper tertile (Group 3). Median FXIII and fibrinogen levels dropped by 33.9% and 34.2%, respectively, during CPB. No association between FXIII activity and the extent of postoperative bleeding was found. However, chest tube bleeding was significantly correlated with preoperative and postoperative fibrinogen. This was confirmed by comparing Groups 1 and 3. Group 3 patients had significantly lower fibrinogen levels than Group 1 at T1 - T4, although most fibrinogen values were within or above the reference range (medians, g/l: 3.5 vs. 4.0, p = 0.043 at T1; 2.3 vs. 2.7, p = 0.015 at T2; 2.9 vs. 3.3, p = 0.008 at T3; 4.2 vs. 5.2, p = 0.002 at T4). There was also a significant relationship of platelet count, PT and APTT, as measured after CPB (T2), with postoperative chest tube drainage. In conclusion, plasma FXIII activity does not influence postoperative bleeding in patients undergoing CPB surgery. There is however an inverse association between preoperative or postoperative plasma fibrinogen levels and postoperative bleeding. These findings indicate a modulation of postoperative bleeding by fibrinogen levels.

  2. Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis.

    PubMed

    Roques, Marjorie; Chretien, Marie Lorraine; Favennec, Camille; Lafon, Ingrid; Ferrant, Emmanuelle; Legouge, Caroline; Plocque, Alexia; Golfier, Camille; Duvillard, Laurence; Amoureux, Lucie; Bastie, Jean Noel; Maurin-Bernier, Lory; Dalle, Frederic; Caillot, Denis

    2016-06-01

    Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C-reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n = 77) or PM (n = 17) from D-12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D-12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5 μg l(-1) , respectively, while CRP was >50, 75 and 100 mg l(-1) in 84%, 70% and 57% and Fib was >4, 5 and 6 g l(-1) in 96%, 80% and 61% of cases respectively (P < 10(-7) ). The same trends were observed from D1 to D12. Overall, between D-12 and D12, only 6.4% of patients had PCT >1.5 μg l(-1) , while CRP >100 mg l(-1) and Fib >6 g l(-1) were observed in 80% and 75% of cases respectively (P < 10(-7) ). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low. © 2016 Blackwell Verlag GmbH.

  3. Circulating tumour cells are linked to plasma D-dimer levels in patients with metastatic breast cancer.

    PubMed

    Mego, Michal; Zuo, Zhuang; Gao, Hui; Cohen, Evan N; Giordano, Antonio; Tin, Sanda; Anfossi, Simone; Jackson, Summer; Woodward, Wendy; Ueno, Naoto T; Valero, Vicente; Alvarez, Ricardo H; Hortobagyi, Gabriel N; Khoury, Joseph D; Cristofanilli, Massimo; Reuben, James M

    2015-03-01

    Cancer is a risk factor for venous thromboembolism (VTE). Elevated plasma D-dimer and fibrinogen levels are also risk factors for VTE. Furthermore, in patients with metastatic breast cancer (MBC), the presence of circulating tumour cells (CTCs) is a risk factor for VTE. The relationship between CTCs and D-dimer is unknown. The aim of this study was to determine whether CTCs correlate with plasma D-dimer level, fibrinogen level, and risk of VTE in MBC. This prospective study included 47 MBC patients treated from July 2009 through December 2010 at the MD Anderson Cancer Center. CTCs in peripheral blood were detected and enumerated using the CellSearch system. D-dimer and fibrinogen were measured in plasma at the time of CTC detection. Thirty-three patients (70 %) had ≥ 1 CTC, and 22 patients (47 %) had ≥ 5 CTCs. Patients with ≥ 1 CTC or ≥ 5 CTCs had significantly higher mean plasma D-dimer levels (µg/mL) than patients with no CTCs and < 5 CTCs (2.48 and 3.31 vs 0.80 and 0.84, respectively; p=0.006 for cut-off ≥ 1 CTC and p=0.003 for cut-off ≥ 5 CTCs). In multivariate analysis, presence of CTCs and number of metastases were positively associated with plasma D-dimer level. CTCs were not associated with plasma fibrinogen level. At median follow-up of 13.5 months, three of 33 patients (9 %) with ≥ 1 CTC had VTE, vs no patients with undetectable CTCs. In conclusion, the presence of CTCs was associated with higher levels of plasma D-dimer in MBC patients. This study further confirms an association between CTCs and risk of VTE.

  4. Gender differences in the expression of erythrocyte aggregation in relation to B beta-fibrinogen gene polymorphisms in apparently healthy individuals.

    PubMed

    Ben Assayag, Einor; Bova, Irena; Berliner, Shlomo; Peretz, Hava; Usher, Sali; Shapira, Itzhak; Bornstein, Natan M

    2006-03-01

    An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the B beta-fibrinogen -455 G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease. The purpose of this study was to investigate the influence of the beta-fibrinogen -455 G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the B beta-fibrinogen -455 G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the -455 A allele compared to subjects with the -455 GG genotype. This association did not exist in women carrying the fibrinogen -455 A allele. The -455 GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the -455 GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the B beta-fibrinogen -455 A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia and a functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.

  5. Chronic subdural hematoma in a patient with congenital afibrinogenemia successfully treated with fibrinogen replacement.

    PubMed

    Sakai, Naoto; Akamine, Soichi; Tokuyama, Tsutomu; Sugiyama, Kenji; Kanayama, Naohiro; Namba, Hiroki

    2011-01-01

    A 37-year-old woman with congenital afibrinogenemia presented with chronic subdural hematoma (CSDH) manifesting as severe headache, nausea, and somnolence after a minor head trauma. Brain computed tomography scans showed a right subdural hematoma associated with midline shift. Laboratory studies showed prolongation of prothrombin time, activated partial thromboplastin time, and undetectably low level of fibrinogen. Until the present episode, she had received plasma-derived fibrinogen concentrate around menstruation and pregnancy. She had also suffered from spinal cord infarction due to vertebral artery occlusion. Burr-hole evacuation and drainage of CSDH was successfully performed using fibrinogen concentrate. The development of CSDH with afibrinogenemia is very rare. Although the past repeated administrations of fibrinogen concentrate were suspected to generate CSDH, paradoxical thrombotic complications caused by upregulation of prothrombin activation, thrombin generation, and growth factors released from platelets might be related to the development of CSDH with congenital afibrinogenemia.

  6. Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.

    PubMed

    Dehghan, Abbas; Yang, Qiong; Peters, Annette; Basu, Saonli; Bis, Joshua C; Rudnicka, Alicja R; Kavousi, Maryam; Chen, Ming-Huei; Baumert, Jens; Lowe, Gordon D O; McKnight, Barbara; Tang, Weihong; de Maat, Moniek; Larson, Martin G; Eyhermendy, Susana; McArdle, Wendy L; Lumley, Thomas; Pankow, James S; Hofman, Albert; Massaro, Joseph M; Rivadeneira, Fernando; Kolz, Melanie; Taylor, Kent D; van Duijn, Cornelia M; Kathiresan, Sekar; Illig, Thomas; Aulchenko, Yurii S; Volcik, Kelly A; Johnson, Andrew D; Uitterlinden, Andre G; Tofler, Geoffrey H; Gieger, Christian; Psaty, Bruce M; Couper, David J; Boerwinkle, Eric; Koenig, Wolfgang; O'Donnell, Christopher J; Witteman, Jacqueline C; Strachan, David P; Smith, Nicholas L; Folsom, Aaron R

    2009-04-01

    Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels. We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg Study, and the British 1958 Birth Cohort Study, including 22 096 participants of European ancestry. Four loci were marked by 1 or more single-nucleotide polymorphisms that demonstrated genome-wide significance (P<5.0 x 10(-8)). These included a single-nucleotide polymorphism located in the fibrinogen beta chain (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of FGB (P=1.8 x 10(-30)), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3 x 10(-15)), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9 x 10(-10)), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04 x 10(-8)). Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.

  7. Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentrations: A systematic review and meta-analysis.

    PubMed

    Sahebkar, Amirhossein; Serban, Maria-Corina; Mikhailidis, Dimitri P; Toth, Peter P; Muntner, Paul; Ursoniu, Sorin; Mosterou, Svetlana; Glasser, Stephen; Martin, Seth S; Jones, Steven R; Rizzo, Manfredi; Rysz, Jacek; Sniderman, Allan D; Pencina, Michael J; Banach, Maciej

    2016-01-01

    Several studies suggest differences between fibrates and statins in lowering plasma fibrinogen (Fib) concentrations, but the evidence is not definitive. Therefore, the aim of this meta-analysis of head-to-head randomized trials was to compare the efficacy of statins and fibrates on plasma Fib concentrations. The literature search included Medline, Scopus, and Web of Science up to February 1st, 2015, to identify head-to-head comparative randomized trials investigating the efficacy of fibrates vs statins on plasma Fib concentrations. In total 22 trials with 2762 participants were included to the meta-analysis. Random-effect meta-analysis suggested a significantly greater effect of fibrates vs statins in lowering plasma Fib concentrations (weighted mean difference [WMD]: -40.7mg/dL, 95% confidence interval [CI]: -55.2, -26.3, p<0.001). When the analysis was stratified according to the type of fibrate administered, there were significant Fib-lowering effects with both bezafibrate (n=8 treatment arms; WMD: -23.7mg/dL, 95% CI: -41.8, -5.7, p=0.01) and fenofibrate (n=15 treatment arms; WMD: -43.7mg/dL, 95% CI: -61.3, -26.2, p<0.001). Overall, there was a numerically greater effect in the subgroup of trials with ≥12 weeks duration (n=17 treatment arms; WMD: -42.7mg/dL, 95% CI: -60.3, -25.1, p<0.001) compared with the subgroup of trials lasting <12 weeks (n=7 treatment arms; WMD: -36.7mg/dL, 95% CI: -52.0, -21.4, p<0.001). Monotherapy with either fibrates or statins suggested a significantly greater effect of fibrates in lowering plasma Fib concentrations. According to these findings, mechanisms associated with fibrinogen metabolism might be responsible for the distinct effects of statins and fibrates in reducing cardiovascular endpoints. Copyright © 2015. Published by Elsevier Ltd.

  8. Diagnosis of congenital fibrinogen disorders.

    PubMed

    Lebreton, Aurélien; Casini, Alessandro

    2016-08-01

    Congenital fibrinogen disorders comprise quantitative disorders defined by a complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia) of circulating fibrinogen and qualitative disorders characterized by a discrepancy between the activity and the antigenic levels of fibrinogen (dysfibrinogenemia and hypodysfibrinogenemia). The biological diagnosis is based on a standard haemostasis assessment. All the coagulation tests that depend on the formation of fibrin as the end point are affected; although in dysfibrinogenemia the specificity and sensitivity of routine test depend on reagent and techniques. A genetic exploration permits to confirm the diagnosis and may enhance the prediction of the patient's phenotype. Homozygous or composite heterozygous null mutations are most often responsible for afibrinogenemia while hypofibrinogenemic patients are mainly heterozygous carrier of an afibrinogenemic allele. Heterozygous missense mutations are prevalent in dysfibrinogenemia, with two hot spot localized in exon 2 of the FGA and in the exon 8 of the FGG. The correlation between phenotype and genotype has been identified in some fibrinogen variants, including six mutations clustered in exons 8 and 9 of the FGG leading to hypofibrinogenemia with hepatic inclusions of abnormal fibrinogen aggregates as well as a few mutations associated with an increase risk of thrombotic events. A familial screening and additional functional assays should be carried out when possible.

  9. The Effect of Reagents Mimicking Oxidative Stress on Fibrinogen Function

    PubMed Central

    Štikarová, Jana; Kotlín, Roman; Riedel, Tomáš; Suttnar, Jiří; Pimková, Kristýna; Chrastinová, Leona; Dyr, Jan E.

    2013-01-01

    Fibrinogen is one of the plasma proteins most susceptible to oxidative modification. It has been suggested that modification of fibrinogen may cause thrombotic/bleeding complications associated with many pathophysiological states of organism. We exposed fibrinogen molecules to three different modification reagents—malondialdehyde, sodium hypochlorite, and peroxynitrite—that are presented to various degrees in different stages of oxidative stress. We studied the changes in fibrin network formation and platelet interactions with modified fibrinogens under flow conditions. The fastest modification of fibrinogen was caused by hypochlorite. Fibers from fibrinogen modified with either reagent were thinner in comparison with control fibers. We found that platelet dynamic adhesion was significantly lower on fibrinogen modified with malondialdehyde and significantly higher on fibrinogen modified either with hypochlorite or peroxynitrite reflecting different prothrombotic/antithrombotic properties of oxidatively modified fibrinogens. It seems that, in the complex reactions ongoing in living organisms at conditions of oxidation stress, hypochlorite modifies proteins (e.g., fibrinogen) faster and more preferentially than malondialdehyde. It suggests that the prothrombotic effects of prior fibrinogen modifications may outweigh the antithrombotic effect of malondialdehyde-modified fibrinogen in real living systems. PMID:24235886

  10. The effect of reagents mimicking oxidative stress on fibrinogen function.

    PubMed

    Štikarová, Jana; Kotlín, Roman; Riedel, Tomáš; Suttnar, Jiří; Pimková, Kristýna; Chrastinová, Leona; Dyr, Jan E

    2013-01-01

    Fibrinogen is one of the plasma proteins most susceptible to oxidative modification. It has been suggested that modification of fibrinogen may cause thrombotic/bleeding complications associated with many pathophysiological states of organism. We exposed fibrinogen molecules to three different modification reagents-malondialdehyde, sodium hypochlorite, and peroxynitrite-that are presented to various degrees in different stages of oxidative stress. We studied the changes in fibrin network formation and platelet interactions with modified fibrinogens under flow conditions. The fastest modification of fibrinogen was caused by hypochlorite. Fibers from fibrinogen modified with either reagent were thinner in comparison with control fibers. We found that platelet dynamic adhesion was significantly lower on fibrinogen modified with malondialdehyde and significantly higher on fibrinogen modified either with hypochlorite or peroxynitrite reflecting different prothrombotic/antithrombotic properties of oxidatively modified fibrinogens. It seems that, in the complex reactions ongoing in living organisms at conditions of oxidation stress, hypochlorite modifies proteins (e.g., fibrinogen) faster and more preferentially than malondialdehyde. It suggests that the prothrombotic effects of prior fibrinogen modifications may outweigh the antithrombotic effect of malondialdehyde-modified fibrinogen in real living systems.

  11. The down-regulation of IL-6-stimulated fibrinogen steady state mRNA and protein levels by human recombinant IL-1 is not PGE2-dependent: effects of IL-1 receptor antagonist (IL-1RA).

    PubMed

    Conti, P; Bartle, L; Barbacane, R C; Reale, M; Sipe, J D

    1995-01-26

    Infections, trauma and inflammatory processes induce a host response with increases in a large group of structurally and functionally diverse plasma proteins. Parental administration of foreign proteins also induce an increase in plasma fibrinogen. Interleukin-6 (IL-6) is a monocyte-derived mediator and has regulatory effects on acute phase protein genes which result in the induction of fibrinogen synthesis in primary hepatocytes, while the addition of interleukin-1 (IL-1) exerts a negative modulating influence on the IL-6-stimulated fibrinogen. In order to understand the mechanisms by which IL-1 inhibits IL-6-stimulated fibrinogen transcription and translation, and since IL-1 is believed to act through PGE2 stimulation, we have studied the influence of PGE2 in IL-6 or IL-1, alone and in combination, on Fg mRNA expression (by Northern blot analysis) and the influence of PGE2, indomethacin, and arachidonic acid on Fg secretion. Moreover, since human recombinant interleukin-1 receptor antagonist (hrIL-1ra) is a strong inhibitor of IL-1 induced IL-1 transcription and translation and has an inhibitory effect on PGE2, we have studied the effects of IL-1ra on the down-regulation of IL-6 stimulated fibrinogen by IL-1, using an Fg ELISA method.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Platelet glycoproteins and fibrinogen in recovery from idiopathic sudden hearing loss.

    PubMed

    Weiss, Daniel; Neuner, Bruno; Gorzelniak, Kerstin; Bremer, Alexis; Rudack, Claudia; Walter, Michael

    2014-01-01

    The pathomechanism and location of idiopathic sudden sensorineural hearing loss (ISSHL) is unclear. In a previous case-control study, we found elevated fibrinogen concentrations and a higher prevalence of T allele carriers of the glycoprotein (Gp) Ia C807T polymorphism in ISSHL patients. 127 patients with ISSHL (mean age 53.3 years, 48.8% females), who underwent a standard therapy with high dose steroids, pentoxifyllin and sterofundine over 8 days were included. We examined the influence of GpIa genotype and fibrinogen (BclI-, A312-, HaeIII-) genotype and fibrinogen plasma levels on hearing recovery after 8 weeks (change from baseline: 0 dB  =  no recovery, >0 to 10 dB = moderate recovery, >10 dB = good recovery). In a subsample of 59 patients with ISSHL, we further studied the association of platelet glycoprotein GpIa, Ib and IIIa densities on hearing recovery as well as the possible effect-modification of platelet glycoproteins on hearing recovery by plasma fibrinogen. In univariate analysis, neither the GpIa genotype nor fibrinogen genotype (all p>0.1) but lower fibrinogen levels (p = 0.029), less vertigo (p = 0.002) and lower GpIIIa receptor density (p = 0.037, n = 59) were associated with hearing recovery. In multivariate analysis, fibrinogen significantly modified the effect of GPIa receptor density on good hearing recovery (effect-modification on multiplicative scale OR = 0.45 (95% confidence interval (0.21-0.94)), p = 0.03). GPIb receptor density below the mean was associated with a 2-fold increase in good hearing recovery both in patients with fibrinogen levels above (p = 0.04) as well as in patients with fibrinogen levels below the mean (p = 0.06). There was no indication for an effect-modification (p = 0.97). The findings suggest a vascular/rheological origin of ISSHL with unique features of thrombosis in the inner ear artery that may include complex interrelationships among platelet glycoproteins and

  13. Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

    PubMed Central

    Schlimp, Christoph J.; Solomon, Cristina; Keibl, Claudia; Zipperle, Johannes; Nürnberger, Sylvia; Öhlinger, Wolfgang; Redl, Heinz; Schöchl, Herbert

    2014-01-01

    BACKGROUND Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration. METHODS This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry. RESULTS All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site. CONCLUSION This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would

  14. A novel fibrinogen Bbeta chain frameshift mutation in a patient with severe congenital hypofibrinogenaemia.

    PubMed

    Xu, Xiucai; Wu, Jingsheng; Zhai, Zhimin; Zhou, Rongfu; Wang, Xuefeng; Wang, Hongli; Ding, Kaiyang; Sun, Zimin; Ni, Heyu

    2006-06-01

    Congenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients' plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aalpha chain. In this study, we identified a genetic defect in the fibrinogen Bbeta-chain (FGB) underlying severe hypofibrinogenemia. The propositus frequently displayed bleeding episodes with a prolonged blood-clotting time (thrombin time > 180 s, activated partial thromboplastin time > 300 s, prothrombin time > 120 s) and had a very low level of plasma fibrinogen (1.7-1.8 mg/dl). His parents had a consanguineous marriage, and their functional and immunological fibrinogen was approximately half of the normal level. The platelet fibrinogen level of the propositus could not be detected by western blotting, and his platelet aggregation was severely impaired. DNA screening of the whole fibrinogen gene revealed a homozygous GGGG-->GGG mutation at nucleotide 7,969-7,972 in his FGB gene. The propositus' parents are both heterozygous for this mutation. This mutation contributes to Gly419-->Val, and the 419-434 codons are frame shifted, and a stop codon is formed at codon 435. The predicted truncated Bbeta-chain is 27 amino acids shorter than the normal Bbeta-chain and a central beta-strand in the globular betaC domain is absent, which may lead to destabilization of the entire beta-domain. To the best of our knowledge, this is the first report of such a mutation which is associated with severe hypofibrinogenemia.

  15. Inverse correlation between fibrinogen and bone mineral density in women: Preliminary findings.

    PubMed

    Chen, Jui-Tung; Kotani, Kazuhiko

    2016-01-01

    Hemostatic factors may be involved in bone health. The present preliminary study investigated the association between plasma fibrinogen and bone mineral density (BMD) in perimenopausal women. A significant inverse correlation between fibrinogen and BMD was observed (correlation coefficient = -0.42, p < 0.01). This correlation appeared to be more clearly observed in the subgroup with a high level of high-sensitivity C-reactive protein than in that with a low level of high-sensitivity C-reactive protein, and in the subgroup with a high level of diacron reactive oxygen metabolites (an oxidative stress marker) than in that with a low level of diacron reactive oxygen metabolites. Thus, fibrinogen may be a possible marker of BMD in this population. More studies on the associations among hemostasis, inflammation, oxidative stress, and bone metabolism are warranted in the clinical setting.

  16. Optimized microturbidimetric assay for fibrinogen.

    PubMed

    Macart, M; Koffi, A; Henocque, G; Mathieu, J F; Guilbaud, J C

    1989-02-01

    In this assay we measure the turbidity produced by precipitation of plasma fibrinogen with a reagent composed of ammonium sulfate, EDTA, and guanidine hydrochloride. The two-step reagent addition, and use of fixed reaction times, eliminates interference from bilirubin, hemoglobin, and chylomicrons. We checked 135 monoclonal proteins for interference, finding the probability of encountering major interference in samples from adults to be very low, P = 0.0002. The method is calibrated with purified fibrinogen and the response is linear over the range 0-10 g/L. Within-run precision (CV) is less than 2% from 1 to 10 g/L. Correlations with the immunoturbidimetric (r = 0.99), chronometric (r = 0.99), and clotting (r = 0.97) methods were extremely high.

  17. Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes

    PubMed Central

    Kim, C.; Christophi, C. A.; Goldberg, R. B.; Perreault, L.; Dabelea, D.; Marcovina, S. M.; Pi-Sunyer, X.; Barrett-Connor, E.

    2015-01-01

    Aim To examine concentrations of biomarkers (adiponectin, C-reactive protein, fibrinogen and tissue plasminogen-activator antigen) associated with glucose homeostasis and diabetes risk by history of gestational diabetes. Methods We conducted a secondary analysis of the Diabetes Prevention Program, a randomized trial of lifestyle intervention or metformin for diabetes prevention. At baseline, participants were overweight and had impaired glucose tolerance. Biomarkers at baseline and 1 year after enrolment were compared between parous women with (n=350) and without a history of gestational diabetes (n=1466). Cox proportional hazard models evaluated whether history of gestational diabetes was associated with diabetes risk, after adjustment for baseline biomarker levels as well as for change in biomarker levels, demographic factors and anthropometrics. Results At baseline, women with histories of gestational diabetes had lower adiponectin (7.5 μg/ml vs. 8.7 μg/ml; p<0.0001) and greater log C-reactive protein (−0.90 mg/l vs. −0.78 mg/l, p=0.04) levels than women without histories of gestational diabetes, but these associations did not persist after adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator antigen were similar between women with and without histories of gestational diabetes. Women with and without histories of gestational diabetes had a similar pattern of changes in biomarkers within randomization arm. Adjustment for age, race/ethnicity, baseline weight, change in weight, baseline biomarker level and change in biomarker level did not significantly alter the association between history of gestational diabetes and diabetes risk. Conclusions Among women with impaired glucose tolerance, biomarkers in women with and without histories of gestational diabetes are similar and respond similarly to lifestyle changes and metformin. Adjustment for biomarker levels did not explain the higher risk of diabetes observed in women with

  18. A Multi-Ethnic Meta-Analysis of Genome-Wide Association Studies in Over 100,000 Subjects Identifies 23 Fibrinogen-Associated Loci but no Strong Evidence of a Causal Association between Circulating Fibrinogen and Cardiovascular Disease

    PubMed Central

    Sabater-Lleal, Maria; Huang, Jie; Chasman, Daniel; Naitza, Silvia; Dehghan, Abbas; Johnson, Andrew D; Teumer, Alexander; Reiner, Alex P; Folkersen, Lasse; Basu, Saonli; Rudnicka, Alicja R; Trompet, Stella; Mälarstig, Anders; Baumert, Jens; Bis, Joshua C.; Guo, Xiuqing; Hottenga, Jouke J; Shin, So-Youn; Lopez, Lorna M; Lahti, Jari; Tanaka, Toshiko; Yanek, Lisa R; Oudot-Mellakh, Tiphaine; Wilson, James F; Navarro, Pau; Huffman, Jennifer E; Zemunik, Tatijana; Redline, Susan; Mehra, Reena; Pulanic, Drazen; Rudan, Igor; Wright, Alan F; Kolcic, Ivana; Polasek, Ozren; Wild, Sarah H; Campbell, Harry; Curb, J David; Wallace, Robert; Liu, Simin; Eaton, Charles B.; Becker, Diane M.; Becker, Lewis C.; Bandinelli, Stefania; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Fornage, Myriam; Green, David; Gross, Myron; Davies, Gail; Harris, Sarah E; Liewald, David C; Starr, John M; Williams, Frances M.K.; Grant, P.J.; Spector, Timothy D.; Strawbridge, Rona J; Silveira, Angela; Sennblad, Bengt; Rivadeneira, Fernando; Uitterlinden, Andre G; Franco, Oscar H; Hofman, Albert; van Dongen, Jenny; Willemsen, G; Boomsma, Dorret I; Yao, Jie; Jenny, Nancy Swords; Haritunians, Talin; McKnight, Barbara; Lumley, Thomas; Taylor, Kent D; Rotter, Jerome I; Psaty, Bruce M; Peters, Annette; Gieger, Christian; Illig, Thomas; Grotevendt, Anne; Homuth, Georg; Völzke, Henry; Kocher, Thomas; Goel, Anuj; Franzosi, Maria Grazia; Seedorf, Udo; Clarke, Robert; Steri, Maristella; Tarasov, Kirill V; Sanna, Serena; Schlessinger, David; Stott, David J; Sattar, Naveed; Buckley, Brendan M; Rumley, Ann; Lowe, Gordon D; McArdle, Wendy L; Chen, Ming-Huei; Tofler, Geoffrey H; Song, Jaejoon; Boerwinkle, Eric; Folsom, Aaron R.; Rose, Lynda M.; Franco-Cereceda, Anders; Teichert, Martina; Ikram, M Arfan; Mosley, Thomas H; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M.; Sudlow, Cathie L M; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Kooner, Jaspal S.; Danesh, John; Nelson, Christopher P; Erdmann, Jeanette; Reilly, Muredach P.; Kathiresan, Sekar; Schunkert, Heribert; Morange, Pierre-Emmanuel; Ferrucci, Luigi; Eriksson, Johan G; Jacobs, David; Deary, Ian J; Soranzo, Nicole; Witteman, Jacqueline CM; de Geus, Eco JC; Tracy, Russell P.; Hayward, Caroline; Koenig, Wolfgang; Cucca, Francesco; Jukema, J Wouter; Eriksson, Per; Seshadri, Sudha; Markus, Hugh S.; Watkins, Hugh; Samani, Nilesh J; Wallaschofski, Henri; Smith, Nicholas L.; Tregouet, David; Ridker, Paul M.; Tang, Weihong; Strachan, David P.; Hamsten, Anders; O’Donnell, Christopher J.

    2013-01-01

    Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease (CVD), range from 34 to 50%. Genetic variants so far identified by genome-wide association (GWA) studies only explain a small proportion (< 2%) of its variation. Methods and Results We conducted a meta-analysis of 28 GWA studies, including more than 90,000 subjects of European ancestry, the first GWA meta-analysis of fibrinogen levels in 7 African Americans studies totaling 8,289 samples, and a GWA study in Hispanic-Americans totaling 1,366 samples. Evaluation for association of SNPs with clinical outcomes included a total of 40,695 cases and 85,582 controls for coronary artery disease (CAD), 4,752 cases and 24,030 controls for stroke, and 3,208 cases and 46,167 controls for venous thromboembolism (VTE). Overall, we identified 24 genome-wide significant (P<5×10−8) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the three structural fibrinogen genes and pathways related to inflammation, adipocytokines and thyrotrophin-releasing hormone signaling. Whereas lead SNPs in a few loci were significantly associated with CAD, the combined effect of all 24 fibrinogen-associated lead SNPs was not significant for CAD, stroke or VTE. Conclusion We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and CAD, stroke or VTE. PMID:23969696

  19. Antiadhesive effect of fibrinogen: a safeguard for thrombus stability

    PubMed Central

    Lishko, Valeryi K.; Burke, Timothy; Ugarova, Tatiana

    2007-01-01

    The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution. PMID:16849640

  20. Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase.

    PubMed Central

    Riipi, L; Carlson, E

    1990-01-01

    One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN. Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal. Blood taken during this period was negative for C. albicans. The role of tumor necrosis factor (TNF) in C. albicans infections was investigated by measuring the fibrinogen response after the administration of C. albicans or recombinant mouse TNF-alpha. Both challenges resulted in an elevated fibrinogen level. When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C. albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited. C. albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay). It was concluded that C. albicans induces TNF in the mouse. Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C. albicans. PMID:2201637

  1. Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase.

    PubMed

    Riipi, L; Carlson, E

    1990-09-01

    One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN. Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal. Blood taken during this period was negative for C. albicans. The role of tumor necrosis factor (TNF) in C. albicans infections was investigated by measuring the fibrinogen response after the administration of C. albicans or recombinant mouse TNF-alpha. Both challenges resulted in an elevated fibrinogen level. When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C. albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited. C. albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay). It was concluded that C. albicans induces TNF in the mouse. Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C. albicans.

  2. Metabolism of Fibrinogen in Cirrhosis of the Liver

    PubMed Central

    Tytgat, G. N.; Collen, D.; Verstraete, M.

    1971-01-01

    The metabolism of human fibrinogen labeled with radioactive iodine was studied in 50 patients with documented cirrhosis of the liver and in 35 healthy control subjects. Results in cirrhotic subjects were the following: plasma volume 47 ± 10 ml/kg; plasma fibrinogen concentration 250 ± 102 mg/100 ml; total plasma fibrinogen pool 118 ± 59 mg/kg, representing 0.73 ± 0.10 of the total body pool; fibrinogen half-life 2.99 ± 0.59 days; fractional catabolic rate 0.34 ± 0.09 of the plasma pool per day; absolute catabolic rate 39 ± 20 mg/kg per day; fractional transcapillary efflux rate 0.82 ± 0.30 of the plasma pool per day. Results in the control subjects were the following: plasma volume 42 ± 7 ml/kg; plasma fibrinogen concentration 284 ± 71 mg/100 ml; total plasma fibrinogen pool 119 ± 40 mg/kg, representing 0.72 ± 0.07 of the total body pool; fibrinogen half-life 4.14 ± 0.56 days; fractional catabolic rate 0.24 ± 0.04 of the plasma pool per day; absolute catabolic rate 28 ± 9 mg/kg per day; fractional transcapillary efflux rate 0.60 ± 0.26 of the plasma pool per day. A significant difference between cirrhotics and controls was observed for plasma volume, fibrinogen half-life, fractional and total catabolic rates, and transcapillary efflux rate. During heparinization of 10 cirrhotic patients the fibrinogen half-life was prolonged from 3.15 ± 0.69 to 4.59 ± 0.79 days. This was associated with a rise in plasma fibrinogen in six out of eight patients. Heparinization did not influence the fibrinogen half-life in five control subjects. Inhibition of the fibrinolytic system in 17 patients resulted in prolongation of the plasma radioactivity half-life of more than 1 day in only three patients, an incidence comparable with that in five control subjects. These results strongly support the concept of accelerated fibrinogen consumption by a process of disseminated intravascular coagulation in cirrhosis of the liver. PMID:5163179

  3. Effects of long-term developmental patterns of adiposity on levels of C-reactive protein and fibrinogen among North-American men and women: the Spokane Heart Study.

    PubMed

    Hoekstra, Trynke; Barbosa-Leiker, Celestina; Wright, Bruce R; Twisk, Jos W R

    2014-01-01

    This study examined the heterogeneity in BMI development by identifying distinct developmental trajectories. These trajectories were further investigated by relating them to markers of low-grade inflammation later in life. Data from approximately 400 healthy volunteers participating in the Spokane Heart Study were collected in 2-year intervals, and four waves of data were available for the current analyses. Body weight was measured by BMI and low-grade inflammation by high-sensitivity C-reactive protein (CRP) and fibrinogen. Up to date statistical techniques, i.e., latent class growth models, were used to analyse heterogeneity in body weight, and linear regressions were run to analyse possible associations between trajectories of body weight and CRP/fibrinogen levels. Six trajectories were identified (three stable, two increasing, and one decreasing) which differed significantly on CRP/fibrinogen levels, highlighting the importance of weight trajectories. The differences were only partly explained by variations in lifestyle habits.

  4. Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study.

    PubMed

    Nair, Shalini; Nair, Bijesh Ravindran; Vidyasagar, Ajay; Joseph, Mathew

    2016-08-01

    The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures.

  5. Iron modulates the alpha chain of fibrinogen.

    PubMed

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  6. Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen

    PubMed Central

    Burrell, Matthew; Henderson, Simon J.; Ravnefjord, Anna; Schweikart, Fritz; Fowler, Susan B.; Witt, Susanne; Hansson, Kenny M.; Webster, Carl I.

    2016-01-01

    Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer’s disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv) as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT) and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions. PMID:27437944

  7. Glycaemic control improves fibrin network characteristics in type 2 diabetes – A purified fibrinogen model

    PubMed Central

    Pieters, Marlien; Covic, Namukolo; van der Westhuizen, Francois H.; Nagaswami, Chandrasekaran; Baras, Yelena; Loots, Du Toit; Jerling, Johann C.; Elgar, Dale; Edmondson, Kathryn S.; van Zyl, Danie G.; Rheeder, Paul; Weisel, John W.

    2010-01-01

    Summary Diabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 × 10−8 cm2) and lysis rate (3.08 to 3.27 µm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model. PMID:18392327

  8. Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial.

    PubMed

    Bilecen, Süleyman; de Groot, Joris A H; Kalkman, Cor J; Spanjersberg, Alexander J; Brandon Bravo Bruinsma, George J; Moons, Karel G M; Nierich, Arno P

    2017-02-21

    Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding. To determine whether fibrinogen concentrate infusion dosed to achieve a plasma fibrinogen level of 2.5 g/L in high-risk cardiac surgery patients with intraoperative bleeding reduces intraoperative blood loss. A randomized, placebo-controlled, double-blind clinical trial conducted in Isala Zwolle, the Netherlands (February 2011-January 2015), involving patients undergoing elective, high-risk cardiac surgery (ie, combined coronary artery bypass graft [CABG] surgery and valve repair or replacement surgery, the replacement of multiple valves, aortic root reconstruction, or reconstruction of the ascending aorta or aortic arch) with intraoperative bleeding (blood volume between 60 and 250 mL suctioned from the thoracic cavity in a period of 5 minutes) were randomized to receive either fibrinogen concentrate or placebo. Intravenous, single-dose administration of fibrinogen concentrate (n = 60) or placebo (n = 60), targeted to achieve a postinfusion plasma fibrinogen level of 2.5 g/L. The primary outcome was blood loss in milliliters between intervention (ie, after removal of cardiopulmonary bypass) and closure of chest. Safety variables (within 30 days) included: in-hospital mortality, myocardial infarction, cerebrovascular accident or transient ischemic attack, renal insufficiency or failure, venous thromboembolism, pulmonary embolism, and operative complications. Among 120 patients (mean age; 71 [SD, 10] years, 37 women [31%]) included in the study, combined CABG and valve repair or replacement surgery comprised 72% of procedures and had a mean (SD) cardiopulmonary bypass time of 200 minutes (83) minutes. For the primary outcome, median blood loss in the fibrinogen group was 50 mL (interquartile range [IQR], 29-100 mL) compared with 70 mL (IQR, 33-145 mL) in the control group (P = .19), the absolute difference 20 mL (95% CI, -13 to 35 mL). There were 6 cases

  9. Fluoride absorption: independence from plasma fluoride levels

    SciTech Connect

    Whitford, G.M.; Williams, J.L.

    1986-04-01

    The concept that there are physiologic mechanisms to homeostatically regulate plasma fluoride concentrations has been supported by results in the literature suggesting an inverse relationship between plasma fluoride levels and the absorption of the ion from the gastrointestinal tract of the rat. The validity of the relationship was questioned because of possible problems in the experimental design. The present work used four different methods to evaluate the effect of plasma fluoride levels on the absorption of the ion in rats: (i) the percentage of the daily fluoride intake that was excreted in the urine; (ii) the concentration of fluoride in femur epiphyses; (iii) the net areas under the time-plasma fluoride concentration curves after intragastric fluoride doses; and (iv) the residual amounts or fluoride in the gastrointestinal tracts after the intragastric fluoride doses. None of these methods indicated that plasma fluoride levels influence the rate or the degree or fluoride absorption. It was concluded that, unless extremely high plasma fluoride levels are involved (pharmacologic or toxic doses), the absorption of the ion is independent of plasma levels. The results provide further evidence that plasma fluoride concentrations are not homeostatically regulated.

  10. Plasma Ammonia Levels in Newborns with Asphyxia.

    PubMed

    Khalessi, Nasrin; Khosravi, Nastaran; Mirjafari, Maryam; Afsharkhas, Ladan

    2016-01-01

    Perinatal asphyxia may result in hypoxic damage in various body organs, especially in the central nervous system. It could induce cascade of biochemical events leading to the cell death and metabolic changes, eventually may increase plasma ammonia levels. The purpose of this study was to determine the prevalence of hyperammonemia in neonates with asphyxia and to find the relationship between ammonia levels and severity of asphyxia. In this cross-sectional study, we included 100 neonates with perinatal asphyxia in the Neonatal Intensive Care Unit of Ali-Asghar Hospital, Iran University of Medical Science, Tehran, Iran in 2010-2011. All full term patients diagnosed of asphyxia were enrolled. The relationship between plasma ammonia levels and sex, gestational age, birth weight and severity of asphyxia were determined. Data were analyzed using SPSS software. Fifty six percent of neonates were male. The mean gestational age was 38.0± 1.2 wk. Mean plasma ammonia level was 222 ± 100 μg/dl and 20% of the neonates had hyperammonemia. It was not associated with gender, gestational age, birth weight, and asphyxia severity. Six patients died and mean plasma ammonia levels was 206±122 μg/dl. In this group, there was no significant relation between plasma ammonia levels and severity of asphyxia. No significant different was seen between plasma ammonia in dead and lived neonates. According to high prevalence of hyperammonemia in neonatal asphyxia, measurement of plasma ammonia levels, is suggested to improve management of asphyxia.

  11. Systematic review of the efficacy and safety of fibrinogen concentrate substitution in adults.

    PubMed

    Warmuth, M; Mad, P; Wild, C

    2012-05-01

    A sufficient plasma level of fibrinogen is critical for the formation of a fibrin clot and haemostasis in both the perioperative setting and in massive haemorrhage. We assessed the efficacy and safety of fibrinogen concentrate substitution in the perioperative setting and in massive haemorrhage. We conducted a systematic literature search for studies conducted on humans and published in either English or German in several databases from 1985 to 2010. In addition, we screened several web sites for assessments on fibrinogen concentrate substitution and conducted a hand search using Scopus. In terms of efficacy, we included all prospective, controlled studies. Concerning safety, we included all prospective studies. We identified two randomised controlled trials and two non-randomised controlled studies, which included a total of 74 patients. The studies indicate that the administration of fibrinogen concentrate is associated with improved clot firmness and reduction in the substitution of other blood products such as red blood cells, fresh frozen plasma and platelet concentrates, as well as decreased post-operative bleeding and drainage volume. In addition, fibrinogen concentrate administration has been reported to be safe with regard to thrombosis and thromboembolic complications, as well as mortality. However, the studies identified were of poor quality. In conclusion, the results of the available controlled trials suggest that the administration of fibrinogen concentrate was effective and safe. However, because all studies identified were of inadequate quality, these findings need to be confirmed by randomised controlled trials of sufficient size and long-term follow-up. © 2011 Ludwig Boltzmann Institute for Health Technology Assessment Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

  12. Plasma substance P levels in fibrositis.

    PubMed

    Reynolds, W J; Chiu, B; Inman, R D

    1988-12-01

    The mechanism of pain in the fibrositis syndrome is unknown. We measured plasma levels of substance P in 32 patients with fibrositis and 26 sex and age matched controls using a radioimmunoassay. The mean plasma level of substance P in the patients with fibrositis was 371 +/- 91 pg/ml and in controls 397 +/- 84 pg/ml (p = NS). We conclude that determination of plasma levels of substance P in fibrositis is of no diagnostic value. This does not exclude the possible role of substance P as a neurotransmitter in the fibrositis syndrome.

  13. [Plasma homocysteine levels in systemic lupus erythematosus].

    PubMed

    Martínez-Berriotxoa, Agustín; Ruiz-Irastorza, Guillermo; Egurbide Arberas, María Victoria; Rueda Gutiérrez, Miguel; Aguirre Errasti, Ciriaco

    2003-05-17

    Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). An association between hyperhomocysteinemia and increased cardiovascular risk has been reported. On the other hand, renal failure and deficiency of vitamin B12 and/or folic acid are common causes of hyperhomocysteinemia. The aims of this study were to determine plasma total homocystein (tHcy) concentrations in SLE patients and to analyze the association of plasma tHcy with age, sex, plasma creatinine, vitamin B12, folates and total cholesterol, as well as with other clinical conditions linked to atherothrombosis in SLE patients. Fasting plasma levels of tHcy, vitamin B12, folates, total cholesterol and creatinine were measured in 94 SLE patients (11 males, 83 females) and in a control group of 308 healthy volunteers (122 males, 186 females). A review of the medical records of SLE patients was performed. Plasma tHcy concentrations were higher in patients with SLE (median 10.54 (mol/L) than in controls (median 8.49 (mol/L, p < 0.001). Hyperhomocysteinemia (tHcy >=15 (mol/L) was found in 17.02% SLE patients. In a multivariate analysis, plasma creatinine (p < 0.001), total cholesterol (p = 0.038), male sex (p = 0.003) and smoking (p = 0.001) were associated with higher plasma tHcy concentrations. No associations were found between plasma tHcy and hypertension, SLE duration, prednisone therapy and antiphospholipid antibodies. Plasma tHcy concentrations are higher in SLE patients than in healthy controls. High concentrations of plasma creatinine and total plasma cholesterol, male sex and smoking are associated with a higher concentration of plasma tHcy in SLE. Since the clinical consequences of hyperhomocysteinemia are not well established, routine determination of plasmatic tHcy and supplemental therapy in patients with high levels of tHcy are not recommended.

  14. Specific assays of hemostasis proteins: fibrinogen.

    PubMed

    Palareti, G; Maccaferri, M

    1990-01-01

    Fibrinogen levels are considered a useful indicator in several pathological conditions and recent epidemiological studies have indicated a relationship between fibrinogen levels and increased risk of cardiovascular disease. An accurate measurement of this protein is therefore recommended and the Italian Committee for Standardization of Methods in Hematology and Laboratory has carried out a collaborative study to determine accuracy, precision and comparability of results obtained by six different methods, i.e., 1. Blombäck and Blombäck method, 2. clotting assay according to von Clauss, 3. radial immunodiffusion according to Mancini et al., 4. total amount of clottable fibrinogen by means of turbidimetric assay according to Ellis and Stransky, and 5. with ChromotimeSystem, 6. prothrombin time (PT)-derived fibrinogen assay on ACL coagulometer. The most accurate resulted the von Clauss method, but only if calibrated with an internal standard; in fact, when the manufacturer's tables are used, the method proved to be highly inaccurate. The best precision, both intra- and between-laboratory, was obtained by the PT-derived test on ACL. On the basis of this still incomplete evaluation of the CISMEL study data, we can conclude that: i. some methods used in clinical laboratories give accurate results only after adequate calibration; ii. a reference standard pool may be a valid tool for calibration and for a better between-laboratory comparability; iii. a predilution of the samples with high fibrinogen levels seems indicated; iv. automation markedly increases the precision of methods.

  15. Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease

    PubMed Central

    Lominadze, D.; Dean, W. L.; Tyagi, S. C.; Roberts, A. M.

    2009-01-01

    Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. PMID:19723026

  16. Recombinant γT305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'A' and calcium binding sites.

    PubMed

    Ikeda, Minami; Kobayashi, Tamaki; Arai, Shinpei; Mukai, Saki; Takezawa, Yuka; Terasawa, Fumiko; Okumura, Nobuo

    2014-08-01

    We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=0.295), suggesting hypodysfibrinogenemia. DNA sequence analysis was performed, and γT305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant γN308K fibrinogen. DNA sequence analysis revealed a heterozygous γT305A substitution (mature protein residue number). The γT305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1mM calcium ion compared with that of γN308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas γN308Kwas impaired at the latter two sites. Molecular modeling demonstrated that γT305 is localized at a shorter distance than γN308 from the high affinity calcium binding site and hole 'a'. Our findings suggest that γT305 might be important for construction of the overall structure of the γ module of fibrinogen. Substitution of γT305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant γT305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Functional evaluation of an inherited abnormal fibrinogen: fibrinogen “Baltimore”

    PubMed Central

    Beck, Eugene A.; Shainoff, John R.; Vogel, Alfred; Jackson, Dudley P.

    1971-01-01

    The rate of clotting and the rate of development and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concentrations of thrombin. Optimal coagulation and development of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approximately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demonstrated by a decreased amplitude on thromboelastography. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were similar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 Å. A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three functionally different ways: (a) the rate of release of fibrinopeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or complete release of the fibrinopeptides from the defective form in 0.3 M NaCl at pH 7.4; and (c) the defective component possessed a high proportion of phosphorylated, relative to nonphosphorylated, fibrinopeptide A, while the coagulable component contained very little of the phosphorylated peptide (AP). The high phosphate content of the defective component did not appear to be the cause of the abnormality, but may be the

  18. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1.

    PubMed

    Meltzer, Mirjam E; Lisman, Ton; de Groot, Philip G; Meijers, Joost C M; le Cessie, Saskia; Doggen, Carine J M; Rosendaal, Frits R

    2010-07-08

    Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and alpha2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for alpha2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors.

  19. Fibrin Fiber Stiffness Is Strongly Affected by Fiber Diameter, but Not by Fibrinogen Glycation.

    PubMed

    Li, Wei; Sigley, Justin; Pieters, Marlien; Helms, Christine Carlisle; Nagaswami, Chandrasekaran; Weisel, John W; Guthold, Martin

    2016-03-29

    The major structural component of a blood clot is a mesh of fibrin fibers. Our goal was to determine whether fibrinogen glycation and fibrin fiber diameter have an effect on the mechanical properties of single fibrin fibers. We used a combined atomic force microscopy/fluorescence microscopy technique to determine the mechanical properties of individual fibrin fibers formed from blood plasma. Blood samples were taken from uncontrolled diabetic patients as well as age-, gender-, and body-mass-index-matched healthy individuals. The patients then underwent treatment to control blood glucose levels before end blood samples were taken. The fibrinogen glycation of the diabetic patients was reduced from 8.8 to 5.0 mol glucose/mol fibrinogen, and the healthy individuals had a mean fibrinogen glycation of 4.0 mol glucose/mol fibrinogen. We found that fibrinogen glycation had no significant systematic effect on single-fiber modulus, extensibility, or stress relaxation times. However, we did find that the fiber modulus, Y, strongly decreases with increasing fiber diameter, D, as Y∝D(-1.6). Thin fibers can be 100 times stiffer than thick fibers. This is unusual because the modulus is a material constant and should not depend on the sample dimensions (diameter) for homogeneous materials. Our finding, therefore, implies that fibrin fibers do not have a homogeneous cross section of uniformly connected protofibrils, as is commonly thought. Instead, the density of protofibril connections, ρPb, strongly decreases with increasing diameter, as ρPb∝D(-1.6). Thin fibers are denser and/or have more strongly connected protofibrils than thick fibers. This implies that it is easier to dissolve clots that consist of fewer thick fibers than those that consist of many thin fibers, which is consistent with experimental and clinical observations.

  20. Ultrastructural localization of the fibrinogen-binding domain of streptococcal M protein.

    PubMed Central

    Rýc, M; Beachey, E H; Whitnack, E

    1989-01-01

    Binding of fibrinogen to the M protein located on the surface fibrillae of group A streptococci impedes deposition of complement and thus contributes to the virulence of these organisms. We investigated this binding by electron microscopy using postembedding immunogold labeling. Both fibrinogen and its D fragment formed a distinct dense layer in the surface fibrillae, separated by 10 nm from the compact part of the cell wall. Labeling the sections with anti-fibrinogen or anti-fragment D showed that the fibrinogen-binding region lay within a 25-nm segment of the fibrillae beginning approximately 30 nm from the inner surface of the cell wall. The outer surface of the fibrinogen layer could be labeled with antibody to the amino-terminal half of type 24 M protein, indicating that the fibrillar tips remained exposed after fibrinogen binding. The degree of labeling with anti-fibrinogen, determined by gold particle counting, was the same whether the bacterial cells had been incubated with purified fibrinogen or whole plasma. These results indicate that the fibrinogen-binding region lies in the distal (amino-terminal) half of the M protein molecule but excludes the most distal portion, which is the site of epitopes that interact with opsonic anti-M antibody, and that plasma proteins other than fibrinogen, a number of which are known to bind to group A streptococci, do not interfere with fibrinogen binding. Images PMID:2473035

  1. Fibrinogen Recovery in Two Methods of Cryoprecipitate Preparation

    DTIC Science & Technology

    1989-08-01

    volume of isoagglutinins and absence of red blood cells, cryoprecipitate can be transfused without regard for the ABO group or Rh type of the...intervention and support. Treatment for these patients is replacement therapy, supplying fibrinogen through transfusion . The first treatment for...represents the transfusable product. Conversely, loss refers to the fibrinogen or factor VIII that is "lost" into the supernatant plasma and therefore not

  2. Single-molecule surface studies of fibrinogen and DNA on semiconductors

    NASA Astrophysics Data System (ADS)

    Kong, Xianhua

    Understanding of protein adsorption onto non-biological substrates is of fundamental interest in science, but also has great potential technological applications in medical devices and biosensors. This study explores the non-specific interaction, at the single molecule level, of a blood protein and DNA with semiconductor surfaces through the use of a custom built, non rastering electron emission microscope and a scanning probe microscope. The specifics and history of electron emission are described as well as the equipment used in this study. The protein examined in this study is human plasma fibrinogen, which plays an important role in haemostatis and thrombosis, and deoxyribonucleic acid (DNA) is also studied. A novel technique for determining the photothreshold of biomolecules on single molecule level is developed and applied to fibrinogen molecules adsorbed on oxidized silicon surfaces, using photo-electron emission microscopy (PEEM). Three theoretical models are employed and compared to analyze the experimental photothreshold data. The non-specific adsorption of human plasma fibrinogen on oxidized p- and n- type silicon (100) surfaces is investigated to characterize both hydrophobic interactions and electrostatic forces. The experimental results indicate that hydrophobic interactions are one of the driving forces for protein adsorption and the electrostatic interactions also play a role in the height of the fibrinogen molecules adsorbed on the surface. PEEM images establish a photo threshold of 5.0 +/- 0.2 eV for fibrinogen on both n-type and p-type Si (100) surfaces. We suggest that the photothreshold results from surface state associated Fermi level (EF) pinning and there exists negative charge transfer from the adsorbed fibrinogen onto the p-type silicon substrates, while on n-type silicon substrates negative charge is transferred in the opposite direction. The adsorption of deoxyribonucleic acid (DNA) on mica and silicon is studied in liquid and ambient

  3. Comparison of the effects of pulmonary rehabilitation with chest physical therapy on the levels of fibrinogen and albumin in patients with lung cancer awaiting lung resection: a randomized clinical trial

    PubMed Central

    2014-01-01

    Background Systemic inflammation plays an important role in the initiation, promotion, and progression of lung carcinogenesis. In patients with non-small cell lung cancer (NSCLC), fibrinogen levels correlate with neoplasia. Here we compared the effects of pulmonary rehabilitation (PR) with chest physical therapy (CPT) on fibrinogen and albumin levels in patients with LC and previous inflammatory lung disease awaiting lung resection. Methods We conducted a randomized clinical trial with 24 patients who were randomly assigned to Pulmonary Rehabilitation (PR) and Chest Physical Therapy (CPT) groups. Each group underwent training 5 days weekly for 4 weeks. All patients were assessed before and after four weeks of training through clinical assessment, measurement of fibrinogen and albumin levels, spirometry, 6-minute Walk Test (6MWT), quality of life survey, and anxiety and depression scale. PR involved strength and endurance training, and CPT involved lung expansion techniques. Both groups attended educational classes. Results A mixed between-within subjects analysis of variance (ANOVA) revealed a significant interaction between time (before and after intervention) and group (PR vs. CPT) on fibrinogen levels (F(1, 22) = 0.57, p < 0.0001) and a significant main effect of time (F(1, 22) = 0.68, p = 0.004). Changes in albumin levels were not statistically significant relative to the interaction effect between time and group (F(1, 22) = 0.96, p = 0.37) nor the main effects of time (F(1, 22) = 1.00, p = 1.00) and group (F(1, 22 ) = 0.59, p = 0.45). A mixed between-within subjects ANOVA revealed significant interaction effects between time and group for the peak work rate of the unsupported upper limb exercise (F(1, 22) = 0.77, p = 0.02), endurance time (F(1, 22) = 0.60, p = 0.001), levels of anxiety (F(1, 22) = 0.60, p = 0.002) and depression (F(1, 22) = 0.74, p = 0.02), and the SF-36 physical

  4. Hereditary renal amyloidosis with a novel variant fibrinogen.

    PubMed Central

    Uemichi, T; Liepnieks, J J; Benson, M D

    1994-01-01

    Two families with hereditary renal amyloidosis were found to have a novel mutation in the fibrinogen A alpha chain gene. This form of amyloidosis is an autosomal dominant condition characterized by proteinuria, hypertension, and subsequent azotemia. DNAs of patients with amyloidosis were screened for a polymorphism in fibrinogen A alpha chain gene by single-strand conformation polymorphism analysis, and affected individuals from two kindreds were found to have a mutation. Both of these kindreds are American of Irish descent presenting with non-neuropathic, nephropathic amyloidosis in the fifth to the seventh decade of life. DNA sequencing showed a point mutation in the fibrinogen A alpha chain gene that is responsible for substitution of valine for glutamic acid at position 526. By restriction fragment length polymorphism analysis, 7 affected individuals and 14 asymptomatic individuals in these two kindreds were positive for the fibrinogen A alpha chain Val 526 gene. Fibrinogen was isolated from plasma of a heterozygous gene carrier and shown to contain approximately 50% variant fibrinogen. Discovery of this new mutation confirms the association between fibrinogen A alpha chain variant and hereditary renal amyloidosis and establishes a new biochemical subtype of amyloidosis. Images PMID:8113408

  5. Ultrastructural and biochemical analysis of fibrinogen receptors on activated thrombocytes

    SciTech Connect

    O'Toole, E.T.

    1989-01-01

    The present studies have been concerned with the role of fibrinogen and its receptor, GP IIb/IIIa, during the activation and early aggregation of pigeon thrombocytes. Thrombocytes were surface labeled with {sup 125}I then separated on SDS-PAGE. Analysis by gel autoradiography revealed major bands at MW 145 kd and 98 kd, which corresponded to human GPIIb and GPIIIa. Immunologic similarity of the pigeon and human receptor components was established by dot blot analysis using polyclonal antibodies directed against human GPIIb and GPIIIa. Pigeon fibrinogen, isolated by plasma precipitation with PEG-1000 and purified over Sepharose 4B, was used to study receptor-ligand interaction. Separation of pigeon fibrinogen on SDS-PAGE resulted in three peptides having apparent MW of 62kd, 55kd, and 47kd which are comparable to human fibrinogen. Further similarity of human and pigeon fibrinogen was verified by immonodiffusion against an antibody specific for the human protein. The role of fibrinogen and its receptor in thrombocyte function was established by turbidimetric aggregation using thrombin as an agonist under conditions requiring Ca++ and fibrinogen.

  6. Fibrinogen Metabolic Responses to Trauma

    DTIC Science & Technology

    2009-01-13

    intravascular coagulation (DIC), and thrombotic complications [8,10-12]. Based on the limited data avail- able at present, changes in fibrinogen...water at 4°C [48]. Temperature of 32°C was used based on the fact that 100% mortality was observed when the temperature in trauma patients dropped...study. The amount of fibrinogen transfused was calculated based on fibrinogen amount within each blood product, such as fresh whole blood

  7. Plasma level monitoring of antipsychotic drugs.

    PubMed

    Cooper, T B

    1978-01-01

    Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.

  8. Aronia melanocarpa as a protector against nitration of fibrinogen.

    PubMed

    Bijak, Michał; Saluk, Joanna; Antosik, Adam; Ponczek, Michał B; Żbikowska, Halina M; Borowiecka, Marta; Nowak, Paweł

    2013-04-01

    Fibrinogen (Fg) also known as coagulation factor I represents about 4% of the total human plasma proteins. The main function of Fg is its involvement in last phase of blood coagulation cascade, when thrombin-induced conversion of dissolved plasma fibrinogen into an insoluble fibrin clot occurs. The reaction of fibrinogen with peroxynitrite causes both structural modifications and changes of the biological properties of this plasma glycoprotein. Recently, there is an increased interest in the screening of natural products present in fruits, vegetables and herbs for their possible antioxidative activities. Therefore, the aim of our study was to estimate the effect of extract from berries of Aronia melanocarpa against nitrative and oxidative damage induced by peroxynitrite. The extract from A. melanocarpa (0.5-50 μg/ml) added to Fg 10 min before peroxynitrite (100 μM) significantly inhibited both the formation of the high molecular weight protein aggregates and nitration of Fg molecule. The extract also abolished peroxynitrite-induced inhibition of fibrinogen polymerization (by 95% at 50 μg/ml). The obtained results indicate that natural extract from berries of A. melanocarpa has protective effects against peroxynitrite-induced nitrative damage of plasma fibrinogen, and therefore may contribute in the prevention of peroxynitrite-related cardiovascular or inflammatory diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Sensitive Immunoassays of Nitrated Fibrinogen in Human Biofluids

    SciTech Connect

    Tang, Zhiwen; Wu, Hong; Du, Dan; Wang, Jun; Wang, Hua; Qian, Weijun; Bigelow, Diana J.; Pounds, Joel G.; Smith, Richard D.; Lin, Yuehe

    2010-05-05

    Three new sandwich immunoassays for detection of nitrated biomarker have been established with potential applications in biomedical studies and clinical practice. In this study, nitrated human fibrinogen, a potential oxidative stress biomarker for several pathologies, was chosen as the target. To improve the sensitivity and overcome the interference caused by the complexity of human biofluids, we developed three sandwich strategies using various combinations of primary antibody and secondary antibody. All three strategies demonstrated high sensitivity and selectivity towards nitrated forms of fibrinogen in buffer, but their performances were dramatically reduced when tested with human plasma and serum samples. Systematically optimizations were carried out to investigate the effects of numerous factors, including sampling, coating, blocking, and immunoreactions. Our final optimization results indicate that two of these strategies retain sufficient sensitivity and selectivity for use as assays in human physiological samples. Specifically, detection limits reached the pM level and the linear response ranges were up to nM level with a correlation coefficient > 0.99. To our best knowledge, this is the first example of using an electrochemical immunoassay for a nitrated biomarker in a physiological fluid. This novel approach provides a rapid, sensitive, selective, cost efficient and robust bioassay for detection of oxidative stress in pathology and for clinical applications. Moreover, the sandwich strategies developed in this paper can be readily used to establish effective methods targeting other nitration biomarkers.

  10. The interactions of fibrinogen and dextrans with erythrocytes

    PubMed Central

    Rampling, M.; Sirs, John A.

    1972-01-01

    1. The rate of packing of erythrocytes in whole blood, under a centrifugal field of 200 g, has been studied using an automatic recording centrifuge. 2. Reduction of the supernatant fibrinogen concentration, by repeatedly washing the cells, lowers the rate of packing and reduces the cell flexibility. 3. Resuspending the cells in their own plasma or in isotonic solutions containing fibrinogen restores their flexibility. 4. Rouleaux formation has been shown to have no effect on the rate of packing by comparison of blood diluted with plasma, isotonic NaCl or Ringer—Locke solutions. While the degree of rouleaux formation varied with the diluent used, the rate of packing and packed cell haematocrit were the same, for the same dilution. 5. Both formalin and dextran altered the degree of rouleaux formation and reduced erythrocyte flexibility. Dextran was found to act indirectly on the erythrocyte flexibility by reducing the plasma fibrinogen concentration. PMID:5046146

  11. Plasma adropin level in patients with pseudoexfoliation.

    PubMed

    Oğurel, Tevfik; Oğurel, Reyhan; Topuz, Mustafa; Örnek, Nurgül; Örnek, Kemal

    2016-10-01

    The aim of this study was to evaluate plasma adropin levels in patients with pseudoexfoliation (PEX). This retrospective case-control study included 35 patients with PEX and 35 individuals without PEX who served as controls. Plasma adropin levels with triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and haemoglobin A1c (HGBA1C) concentrations were measured in both groups. The mean serum adropin levels were 3.24 ± 0.95 ng/mL (range, 1.90-7.88 ng/mL) in patients with PEX syndrome and 5.78 ± 2.85 ng/mL (range, 2.08-5.41 ng/mL) in PEX glaucoma patients. There was no statistically significant difference in mean adropin levels between PEX syndrome and PEX glaucoma patients. However, similar adropin levels were found in the PEX glaucoma patients and the control group (P > 0.05). The mean serum adropin levels were 3.34 ± 0.89 ng/mL (range, 1.90-5.39 ng/mL) in the PEX group and 5.78 ± 2.85 ng/mL (range, 3.08-11.06 ng/mL) in the control group. The mean serum adropin level of the PEX group was significantly lower than that of the control group (P < 0.001). There were no significant differences between the two groups in terms of serum glucose, total cholesterol, LDL, HDL, HGBA1C, triglycerides levels, or body mass index (all P > 0.05). Adropin level is lower in patients with PEX.

  12. Differential contributions of platelets and fibrinogen to early coagulopathy in a rat model of hemorrhagic shock.

    PubMed

    Letson, Hayley L; Dobson, Geoffrey P

    2016-05-01

    The mechanisms of early traumatic-induced coagulopathy are not well understood. Our aim was to examine the role of platelets and fibrinogen to early coagulopathy in the rat after hemorrhagic shock. Adult Sprague-Dawley rats were anesthetized and randomly assigned to: 1) Baseline, 2) Hemorrhage or 3) Shock (n=10 each). Controlled phlebotomy occurred over 20min and animals were left in shock 60min. Coagulation was assessed using PT, aPTT, ROTEM and ELISAs. PT and aPTT increased 5 to 7 times following hemorrhage and shock. Prolongation of EXTEM and INTEM clotting times, lower clot elasticity and increased EXTEM lysis index (LI) indicated a hypocoagulopathy. After 20min hemorrhage, LI(30-60) in FIBTEM was ~100%, EXTEM 83-87% and APTEM 80-82% indicating a platelet contribution to the coagulopathy with no hyperfibrinolysis. After 60min shock, the situation was reversed with fibrinogen loss being a contributor. This apparent switch from a platelet- to a fibrinogen-based coagulopathy, with fibrinolysis, was supported by ≥15% in maximum lysis (ML), a threefold increase in plasma PAI-1 after hemorrhage, and undetectable levels after shock. Curiously, the relative contribution of fibrinogen/platelet ratio to clot amplitude, determined from FIBTEM/EXTEM A10 ratio (and MCF), remained unchanged at ~1:5 for baseline, hemorrhage and shock despite a progressive hypocoagulopathy. Significant increases in P-selectin, acidosis and lactate indicated systemic endothelial damage and tissue hypoperfusion. Hypocoagulopathy following severe hemorrhage and shock in the rat appeared to involve a two-step process of platelet dysfunction followed by fibrinogen impairment, possibly linked to progressive endothelial dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Investigation of the mechanism(s) involved in decreasing increased fibrinogen activity in hyperglycemic conditions using L-lysine supplementation.

    PubMed

    Mirmiranpour, Hossein; Bathaie, S Zahra; Khaghani, Shahnaz; Nakhjavani, Manouchehr; Kebriaeezadeh, Abbas

    2012-09-01

    Fibrinogen is a plasma glycoprotein that participates in the hemostasis system. Its malfunction has been reported as a consequence of diabetic complications. In this study, the inhibitory effect of L-Lysine (Lys) on the nonenzymatic glycation of fibrinogen was investigated in both in vitro and in vivo conditions. Fibrinogen was incubated with glucose in the presence or absence of Lys. Then, its structure was studied by fluorescence spectroscopy, circular dichroism, and electrophoresis. The Clauss method was used to determine fibrinogen activity. In addition, one of the two groups of type 2 diabetic patients receiving ordinary treatment was additionally treated with Lys for 3 months. Fibrinogen activity and some other parameters were evaluated in their plasma. The results indicated increases in the activity of glycated fibrinogen in both of the in vivo and in vitro experiments. Advanced glycation end products were increased by time, as shown using fluorometry in both the plasma of the diabetic patients and the incubation medium of protein with glucose. The circular dichroism spectra showed some changes in the fibrinogen secondary and tertiary structures after glycation. The electrophoretic mobility of the glycated fibrinogen changed and the cross-link formation between the fibrinogen subunits due to glycation was observed. Lys inhibited all of the mentioned fibrinogen changes both in the in vitro experiments and after its administration to the diabetic patients. Lys, as an inhibitor of protein glycation, improved fibrinogen's structure and function, both in vitro and in vivo. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Fibrin(ogen) mediates acute inflammatory responses to biomaterials

    PubMed Central

    1993-01-01

    Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787

  15. Retrochorionic hematoma in congenital afibrinogenemia: resolution with fibrinogen concentrate infusions.

    PubMed

    Aygören-Pürsün, E; Martinez Saguer, I; Rusicke, E; Louwen, F; Geka, F; Ivaskevicius, V; Oldenburg, J; Klingebiel, T; Kreuz, W

    2007-04-01

    Without treatment, pregnancies in patients with congenital afibrinogenemia terminate in miscarriage at 5-6 weeks of gestation. Animal model studies have suggested that implantation site bleeding contributes to miscarriage in afibrinogenemia; however, retrochorionic hematoma in human congenital afibrinogenemia has not been previously observed. A patient with congenital afibrinogenemia receiving fibrinogen prophylaxis developed a retrochorionic hematoma in the first trimester. With continuous intensified fibrinogen concentrate replacement the hematoma resolved over 6 weeks, and the patient delivered a healthy infant. Median fibrinogen levels in the first trimester were 48 mg/dL and in second and third trimester 44 mg/dL. Median fibrinogen levels under 60 mg/dL may be adequate to maintain pregnancy in patients with congenital afibrinogenemia, although it is possible that higher levels might reduce the risk of hemorrhagic events.

  16. The role of fibrinogen and haemostatic assessment in postpartum haemorrhage: preparations for a randomised controlled trial.

    PubMed

    Wikkelsø, Anne Juul

    2015-04-01

    Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH) and subsequent severity of bleeding. Fibrinogen concentrate may be prescribed to correct acquired hypofibrinogenaemia, but evidence is lacking regarding the treatment efficacy. This thesis assesses the current evidence for the use of fibrinogen concentrate and haemostatic assessment in bleeding patients with special attention to the obstetrical population. It includes five papers: In Paper I the benefits or harms of fibrinogen concentrate in bleeding patients in general was evaluated using a systematic Cochrane review methodology with metaanalysis of all published randomized controlled trials (RCTs). Six trials with high risk of bias were included (248 patients). Fibrinogen appeared to reduce the need of allogenic transfusions by 53%. However, the included trials were conducted only in an elective surgical setting with a population of mainly cardiac surgical patients. Paper II was also a systematic review based on Cochrane methodology evaluating the use of viscoelastic haemostatic assays to guide haemostatic transfusion in bleeding patients. Nine RCTs (776 patients) with high risk of bias were included primarily in elective cardiac surgical patients and none were specific for the obstetric subpopulation. Viscoelastic haemostatic assay guided transfusion algorithm reduced blood loss and the proportion of patients exposed to fresh frozen plasma (FFP) or platelets. In both studies, we were unable to make firm conclusion on our primary outcome, "all cause mortality" due to lack of adequate data. Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed

  17. Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death.

    PubMed

    Ill-Raga, Gerard; Palomer, Ernest; Ramos-Fernández, Eva; Guix, Francesc X; Bosch-Morató, Mònica; Guivernau, Biuse; Tajes, Marta; Valls-Comamala, Victòria; Jiménez-Conde, Jordi; Ois, Angel; Pérez-Asensio, Fernando; Reyes-Navarro, Mario; Caballo, Carolina; Gil-Gómez, Gabriel; Lopez-Vilchez, Irene; Galan, Ana M; Alameda, Francesc; Escolar, Gines; Opazo, Carlos; Planas, Anna M; Roquer, Jaume; Valverde, Miguel A; Muñoz, Francisco J

    2015-03-01

    Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parenchyma after ischemic stroke. Therefore, we assayed the toxicity of fibrinogen and nitrotyrosinated fibrinogen in a human neuroblastoma cell line. For that purpose we measured the activity of caspase-3, a key enzyme in the apoptotic pathway, and cell survival. We found that nitrotyrosinated fibrinogen induced higher activation of caspase 3. Accordingly, cell survival assays showed a more neurotoxic effect of nitrotyrosinated fibrinogen at all concentrations tested. In summary, nitrotyrosinated fibrinogen would be of pathophysiological interest in ischemic stroke due to both its impact on hemostasis - it impairs thrombolysis, the main target in stroke treatments - and its neurotoxicity that would contribute to the death of the brain tissue surrounding the infarcted area.

  18. Formation and cell translocation of carbon nanotube-fibrinogen protein corona

    NASA Astrophysics Data System (ADS)

    Chen, Ran; Radic, Slaven; Choudhary, Poonam; Ledwell, Kimberley G.; Huang, George; Brown, Jared M.; Chun Ke, Pu

    2012-09-01

    The binding of plasma fibrinogen with both single-walled and multi-walled carbon nanotubes (SWNTs and MWNTs) has been examined. Specifically, our absorbance study indicated that MWNTs were coated with multi-layers of fibrinogen to render a "hard protein corona," while SWNTs were adsorbed with thin layers of the protein to precipitate out of the aqueous phase. In addition, static quenching as a result of energy transfer from fluorescently labeled fibrinogen to their nanotube substrates was revealed by Stern-Volmer analysis. When exposed to HT-29 cells, the nanotubes and fibrinogen could readily dissociate, possibly stemming from their differential affinities for the amphiphilic membrane bilayer.

  19. Fibrinogen and the Severity of Coronary Atherosclerosis among Adults with and without Statin Treatment: Lipid as a mediator.

    PubMed

    Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Li, Sha; Xu, Rui-Xia; Dong, Qian; Li, Jian-Jun

    2016-06-01

    It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators. We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated. Fibrinogen was positively associated with GS after adjustment (β=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450-3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status. The increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All

  20. Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease

    PubMed Central

    Duvoix, Annelyse; Dickens, Jenny; Haq, Imran; Mannino, David; Miller, Bruce; Tal-Singer, Ruth

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV1. However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker. Methods Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality. Results There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. Conclusions Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. PMID:22744884

  1. Fibrinogen stability under surfactant interaction.

    PubMed

    Hassan, Natalia; Barbosa, Leandro R S; Itri, Rosangela; Ruso, Juan M

    2011-10-01

    Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen's secondary structure is affected by all three studied surfactants (decrease in α-helix and an increase in β-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Fibrinogen and platelet contributions to clot formation: implications for trauma resuscitation and thromboprophylaxis.

    PubMed

    Kornblith, Lucy Z; Kutcher, Matthew E; Redick, Brittney J; Calfee, Carolyn S; Vilardi, Ryan F; Cohen, Mitchell Jay

    2014-02-01

    Thromboelastography (TEG) is used to diagnose perturbations in clot formation and lysis that are characteristic of acute traumatic coagulopathy. With novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to clot formation can be elucidated to tailor resuscitation and thromboprophylaxis. We sought to describe the longitudinal contributions of fibrinogen and platelets to clot strength after injury, hypothesizing that low levels of FF and a low contribution of fibrinogen to clot strength on admission would be associated with coagulopathy, increased transfusion requirements, and worse outcomes. A total of 603 longitudinal plasma samples were prospectively collected from 251 critically injured patients at a single Level 1 trauma center from 0 hour to 120 hours. TEG maximal amplitude (MA), FF MA, FF levels, von Clauss fibrinogen, and standard coagulation measures were performed in parallel. Percentage contributions of FF (%MA(FF)) and platelets (%MA(platelets)) were calculated as each MA divided by overall kaolin TEG MA. Coagulopathic patients (international normalized ratio ≥ 1.3) had significantly lower admission %MA(FF) than noncoagulopathic patients (24.7% vs. 31.2%, p < 0.05). Patients requiring plasma transfusion had a significantly lower admission %MA(FF) (26.6% vs. 30.6%, p < 0.05). Higher admission %MA(FF) was predictive of reduced mortality (hazard ratio, 0.815, p < 0.001). %MA(platelets) was higher than %MA(FF) at all time points, decreased over time, and stabilized at 72 hours (69.4% at 0 hour, 56.2% at 72 hours). In contrast, %MA(FF) increased over time and stabilized at 72 hours (30.6% at 0 hour, 43.8% at 72 hours). FF TEG affords differentiation of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma transfusion were associated with a lower %MA(FF). Despite this importance of fibrinogen, platelets had a greater contribution to clot strength at all time points after injury. This suggests that attention to these

  3. An efficient system for secretory production of fibrinogen using a hepatocellular carcinoma cell line.

    PubMed

    Matsumoto, Michinori; Matsuura, Tomokazu; Aoki, Katsuhiko; Maehashi, Haruka; Iwamoto, Takeo; Ohkawa, Kiyoshi; Yoshida, Kiyotsugu; Yanaga, Katsuhiko; Takada, Koji

    2015-03-01

    Despite an increasing demand, blood products are not always safe because most are derived from blood donations. One possible solution is the development and commercialization of recombinant fibrinogen, but this process remains poorly developed. This study aimed to develop an effective production system for producing risk-free fibrinogen using human hepatocellular cell lines and serum-free media. Three human liver cancer cell lines (HepG2, FLC-4 and FLC-7) were cultivated in a serum-supplemented medium or two serum-free media (ASF104N and IS-RPMI) to compare their fibrinogen secretion abilities. Fibrinogen subunit gene expression was estimated by quantitative polymerase chain reaction. Massive fibrinogen production was induced using a 5-mL radial flow bioreactor (RFB) while monitoring glucose metabolism. Subsequently, fibrinogen's biochemical characteristics derived from these cells were analyzed. FLC-7 cell culture combined with IS-RPMI resulted in significantly better fibrinogen production (21.6 μg/10(7) cells per day). ASF104N had more positive effects on cell growth compared with IS-RPMI, whereas fibrinogen production was more efficient with IS-RPMI than with ASF104N. Changing the medium from ASF104N to IS-RPMI led to significantly increased fibrinogen gene expression and glucose consumption. In the RFB culture, the fibrinogen secretion rate of FLC-7 cells reached 0.73 μg/mL per day during a 42-day cultivation period. The subunit composition and clot formation activity of FLC-7 cell-derived fibrinogen corresponded to those of plasma fibrinogen. The FLC-7 cell culture system is suitable for large-scale fibrinogen preparation production. © 2014 The Japan Society of Hepatology.

  4. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    PubMed

    Yamashita, Karine M; Alves, André F; Barbaro, Katia C; Santoro, Marcelo L

    2014-05-01

    Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering bleeding manifestations in severely-envenomed patients.

  5. Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

    PubMed Central

    Yamashita, Karine M.; Alves, André F.; Barbaro, Katia C.; Santoro, Marcelo L.

    2014-01-01

    Background/Aims Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Methods/Principal Findings Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. Conclusions SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering

  6. Fibrinogen: a journey into biotechnology.

    PubMed

    Bratek-Skicki, Anna; Żeliszewska, Paulina; Ruso, Juan M

    2016-10-26

    Fibrinogen has been known since the mid-nineteenth century. Although initially its interest had been within the field of physiology over time its study has spread to new disciplines such as biochemistry, colloids and interfaces or biotechnology. First, we will describe the bulk properties of the molecule as well as its supramolecular assembly with different ligands by using different techniques and theoretical models. In the next step we will analyze the interfacial properties, an important topic because fibrinogen is considered to be a major inhibitor of lung surfactants' function at the lining layer of alveoli. The final step will be devoted to its main application in biotechnology. Thus, the adsorption of fibrinogen at solid/electrolyte interfaces and at carrier particles will be discussed. The reversibility of adsorption, fibrinogen molecule orientation, and maximum coverage will be thoroughly discussed. The stability of fibrinogen monolayers formed at these surfaces with respect to pH and ionic strength cyclic changes will also be presented. Based on the physicochemical data, adsorption kinetics and colloid particle deposition measurements, probable adsorption mechanisms of fibrinogen on solid/electrolyte interfaces will be defined.

  7. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy

    PubMed Central

    2013-01-01

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage. PMID:24063404

  8. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy.

    PubMed

    Davenport, Ross; Brohi, Karim

    2013-09-24

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage.

  9. Management of congenital quantitative fibrinogen disorders: a Delphi consensus.

    PubMed

    Casini, A; de Moerloose, P

    2016-11-01

    No evidence-based guidelines for the management of patients suffering from afibrinogenaemia and hypofibrinogenaemia are available. The aim of this study was to harmonize patient's care among invited haemophilia experts from Belgium, France and Switzerland. A Delphi-like methodology was used to reach a consensus on: prophylaxis, bleeding, surgery, pregnancy and thrombosis management. The main final statements are as follows: (i) a secondary fibrinogen prophylaxis should be started after a first life-threatening bleeding in patients with afibrinogenaemia; (ii) during prophylaxis the target trough fibrinogen level should be 0.5 g L(-1) ; (iii) if an adaptation of dosage is required, the frequency of infusions rather than the fibrinogen amount should be modified; (iv) afibrinogenaemic patients undergoing a surgery at high bleeding risk should receive fibrinogen concentrates regardless of the personal or family history of bleeding; (v) moderate hypofibrinogenaemic patients (i.e. ≥0.5 g L(-1) ) without previous bleeding (despite haemostatic challenges) undergoing a surgery at low bleeding risk may not receive fibrinogen concentrates as prophylaxis; (vi) monitoring the trough fibrinogen levels should be performed at least once a month throughout the pregnancy and a foetal growth and placenta development close monitoring by ultrasound is recommended; (vii) fibrinogen replacement should be started concomitantly to the introduction of anticoagulation in afibrinogenaemic patients suffering from a venous thromboembolic event; and (viii) low-molecular-weight heparin is the anticoagulant of choice in case of venous thromboembolism. The results of this initiative should help clinicians in the difficult management of patients with congenital fibrinogen disorders. © 2016 John Wiley & Sons Ltd.

  10. Rapid extraction, radioiodination, and in vivo catabolism of 125I-labeled fibrinogen in the horse

    SciTech Connect

    Coyne, C.P.; Hornof, W.J.; Kelly, A.B.; O'Brien, T.R.; DeNardo, S.J.

    1985-12-01

    Two methods were analyzed for the rapid extraction of equine fibrinogen from fresh plasma, using ammonium sulfate-sodium phosphate buffer. Fibrinogen from each of these 2 methods was then radiolabeled with 125I (half-life = 60.2 days, gamma = 35 keV), using monochloroiodine reagent. Mean protein-bound activity was 98.5% and mean clottable radioactivity was 94.1%. Radiolabeled fibrinogen administered IV to 15 horses had an overall mean (+/- SD) plasma half-life of 4.95 +/- 0.44 days.

  11. Clinical Features and Management of Congenital Fibrinogen Deficiencies.

    PubMed

    Casini, Alessandro; de Moerloose, Philippe; Neerman-Arbez, Marguerite

    2016-06-01

    Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) or both (hypodysfibrinogenemia) of plasmatic fibrinogen. Afibrinogenemia is often diagnosed at birth following prolonged umbilical cord bleeding and is characterized by spontaneous bleeding in all tissues, while hypofibrinogenemic patients are more often asymptomatic. Spontaneous spleen ruptures, painful bone cysts, cardiovascular events, and intrahepatic inclusions can complicate the clinical course of patients with quantitative fibrinogen disorders. Clinical manifestations of dysfibrinogenemia are very heterogeneous, from absence of symptoms to major bleeding or thrombosis, chronic thromboembolic pulmonary hypertension, and renal amyloidosis. Hypodysfibrinogenemic patients can suffer from both major bleeding and recurrent thrombosis. Pregnancy of women with congenital fibrinogen disorders is a high-risk situation. Owing to the absence of controlled randomized studies, clinical management is mainly based on expert consensus. For the treatment and/or the prevention of bleeding, plasma-derived fibrinogen concentrates are the optimal choice. Treatment of thrombosis may be challenging. More specifically, management strategies should be tailored to each patient, taking the personal and familial history of bleeding and thrombosis, the genotype, and the specific clinical situation into account. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Concentration-dependent effect of fibrinogen on IgG-specific antigen binding and phagocytosis.

    PubMed

    Boehm, Tobias Konrad; Sojar, Hakimuddin; Denardin, Ernesto

    2010-01-01

    In this paper, we aim to characterize fibrinogen-IgG interactions, and explore how fibrinogen alters IgG-mediated phagocytosis. Using enzyme-linked binding assays, we found that fibrinogen binding to IgG is optimized for surfaces coated with high levels of IgG. Using a similar method, we have shown that for an antigen unable to specifically bind fibrinogen, fibrinogen enhances binding of antibodies towards that antigen. For binding of IgG antibodies to cells expressing Fc receptors, we found a bimodal binding response, where low levels of fibrinogen enhance binding of antibody to Fc receptors and high levels reduce it. This corresponds to a bimodal effect on phagocytosis of IgG-coated particles, which is inhibited in the presence of excess IgG during coating of the particles with antibodies and fibrinogen. We conclude that fibrinogen can modulate phagocytosis of IgG-coated particles in vitro by changing IgG binding behavior, and that high fibrinogen levels could negatively affect phagocytosis.

  13. Optimized preparation method of platelet-concentrated plasma and noncoagulating platelet-derived factor concentrates: maximization of platelet concentration and removal of fibrinogen.

    PubMed

    Araki, Jun; Jona, Masahiro; Eto, Hitomi; Aoi, Noriyuki; Kato, Harunosuke; Suga, Hirotaka; Doi, Kentaro; Yatomi, Yutaka; Yoshimura, Kotaro

    2012-03-01

    Platelet-rich plasma (PRP) has been clinically used as an easily prepared growth factor cocktail that can promote wound healing, angiogenesis, and tissue remodeling. However, the therapeutic effects of PRP are still controversial, due partly to the lack of optimized and standardized preparation protocols. We used whole blood (WB) samples to optimize the preparation protocols for PRP, white blood cell-containing (W-PRP), platelet-concentrated plasma (PCP), and noncoagulating platelet-derived factor concentrate (PFC). PRP and W-PRP were most efficiently collected by 10 min centrifugation in a 15-mL conical tube at 230-270 g and 70 g, respectively. To prepare PCP, platelets were precipitated by centrifugation of PRP at >2300 g, 90% of supernatant plasma was removed, and the platelets were resuspended. For preparation of noncoagulating PFC, the supernatant was replaced with one-tenth volume of saline, followed by platelet activation with thrombin. Platelet (before activation) and platelet-derived growth factor (PDGF)-BB (after activation) concentrations in PCP were approximately 20 times greater than those in WB, whereas PFC contained a 20-times greater concentration of platelets before platelet activation and a 50-times greater concentration of PDGF-BB without formation of a fibrin gel after platelet activation than WB. Surprisingly, total PDGF-BB content in the PFC was twice that of activated WB, which suggested that a substantial portion of the PDGF-BB became trapped in the fibrin glue, and replacement of plasma with saline is crucial for maximization of platelet-derived factors. As an anticoagulant, ethylene di-amine tetra-acetic acid disodium inhibited platelet aggregation more efficiently than acid citrate dextrose solution, resulting in higher nonaggregated platelet yield and final PDGF-BB content. These results increase our understanding of how to optimize and standardize preparation of platelet-derived factors at maximum concentrations.

  14. Optimized Preparation Method of Platelet-Concentrated Plasma and Noncoagulating Platelet-Derived Factor Concentrates: Maximization of Platelet Concentration and Removal of Fibrinogen

    PubMed Central

    Araki, Jun; Jona, Masahiro; Eto, Hitomi; Aoi, Noriyuki; Kato, Harunosuke; Suga, Hirotaka; Doi, Kentaro; Yatomi, Yutaka

    2012-01-01

    Abstract Platelet-rich plasma (PRP) has been clinically used as an easily prepared growth factor cocktail that can promote wound healing, angiogenesis, and tissue remodeling. However, the therapeutic effects of PRP are still controversial, due partly to the lack of optimized and standardized preparation protocols. We used whole blood (WB) samples to optimize the preparation protocols for PRP, white blood cell-containing (W-PRP), platelet-concentrated plasma (PCP), and noncoagulating platelet-derived factor concentrate (PFC). PRP and W-PRP were most efficiently collected by 10 min centrifugation in a 15-mL conical tube at 230–270 g and 70 g, respectively. To prepare PCP, platelets were precipitated by centrifugation of PRP at >2300 g, 90% of supernatant plasma was removed, and the platelets were resuspended. For preparation of noncoagulating PFC, the supernatant was replaced with one-tenth volume of saline, followed by platelet activation with thrombin. Platelet (before activation) and platelet-derived growth factor (PDGF)-BB (after activation) concentrations in PCP were approximately 20 times greater than those in WB, whereas PFC contained a 20-times greater concentration of platelets before platelet activation and a 50-times greater concentration of PDGF-BB without formation of a fibrin gel after platelet activation than WB. Surprisingly, total PDGF-BB content in the PFC was twice that of activated WB, which suggested that a substantial portion of the PDGF-BB became trapped in the fibrin glue, and replacement of plasma with saline is crucial for maximization of platelet-derived factors. As an anticoagulant, ethylene di-amine tetra-acetic acid disodium inhibited platelet aggregation more efficiently than acid citrate dextrose solution, resulting in higher nonaggregated platelet yield and final PDGF-BB content. These results increase our understanding of how to optimize and standardize preparation of platelet-derived factors at maximum concentrations. PMID

  15. Evaluation of serum fibrinogen, plasminogen, α2-anti-plasmin, and plasminogen activator inhibitor levels (PAI) and their correlation with presence of retinopathy in patients with type 1 DM.

    PubMed

    Polat, Sefika Burcak; Ugurlu, Nagihan; Yulek, Fatma; Simavli, Huseyin; Ersoy, Reyhan; Cakir, Bekir; Erel, Ozcan

    2014-01-01

    BACKGROUND. Diabetic retinopathy (DR) is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative) were associated with abnormally modulated hemostatic parameters in patients with T1DM. METHOD. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP. We compared these subgroups with each other and the control group (Group IV) according to the serum fibrinogen, plasminogen, alpha2-anti-plasmin ( α2-anti-plasmin), and PAI. RESULTS. We detected that PAI-1, serum fibrinogen, and plasminogen levels were similar between the diabetic and control groups (P = 0.209, P = 0.224, and P = 0.244, resp.), whereas α2-anti-plasmin was higher in Groups I, II, and III compared to the control group (P < 0.01, P < 0.05, and P < 0.001, resp.). There was a positive correlation between serum α2-anti-plasmin and HbA1c levels (r = 0,268, P = 0.031). CONCLUSION. To our knowledge there is scarce data in the literature about α2-anti-plasmin levels in type 1 diabetes. A positive correlation between α2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control.

  16. Prognostic significance of preoperative fibrinogen in patients with colon cancer

    PubMed Central

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-01-01

    AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and

  17. Prognostic significance of preoperative fibrinogen in patients with colon cancer.

    PubMed

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-07-14

    To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1(st) 2005 to June 1(st) 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and AFP levels correlated

  18. Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts.

    PubMed

    Valvi, Deepa; Mannino, David M; Müllerova, Hana; Tal-Singer, Ruth

    2012-01-01

    Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations. Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95). In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74). Similar findings were seen with continuous fibrinogen levels. In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD.

  19. Fibrinogen, chronic obstructive pulmonary disease (COPD) and outcomes in two United States cohorts

    PubMed Central

    Valvi, Deepa; Mannino, David M; Müllerova, Hana; Tal-Singer, Ruth

    2012-01-01

    Background Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Methods We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations. Results Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79–2.95). In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39–1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27–1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07–1.74). Similar findings were seen with continuous fibrinogen levels. Conclusion In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD. PMID:22419864

  20. The influence of surface chemistry on adsorbed fibrinogen conformation, orientation, fiber formation and platelet adhesion.

    PubMed

    Zhang, Liudi; Casey, Brendan; Galanakis, Dennis K; Marmorat, Clement; Skoog, Shelby; Vorvolakos, Katherine; Simon, Marcia; Rafailovich, Miriam H

    2017-03-02

    Thrombosis is a clear risk when any foreign material is in contact with the bloodstream. Here we propose an immunohistological stain-based model for non-enzymatic clot formation that enables a facile screen for the thrombogenicity of blood-contacting materials. We exposed polymers with different surface chemistries to protease-free human fibrinogen. We observed that on hydrophilic surfaces, fibrinogen is adsorbed via αC regions, while the γ400-411 platelet-binding dodecapeptide on the D region becomes exposed, and fibrinogen fibers do not form. In contrast, fibrinogen is adsorbed on hydrophobic surfaces via the relatively hydrophobic D and E regions, exposing the αC regions while rendering the γ400-411 inaccessible. Fibrinogen adsorbed on hydrophobic surfaces is thus able to recruit other fibrinogen molecules through αC regions and polymerize into large fibrinogen fibers, similar to those formed in vivo in the presence of thrombin. Moreover, the γ400-411 is available only on the large fibers not elsewhere throughout the hydrophobic surface after fibrinogen fiber formation. When these surfaces were exposed to gel-sieved platelets or platelet rich plasma, a uniform monolayer of platelets, which appeared to be activated, was observed on the hydrophilic surfaces. In contrast, large agglomerates of platelets were clustered on fibers on the hydrophobic surfaces, resembling small nucleating thrombi. Endothelial cells were also able to adhere to the monomeric coating of fibrinogen on hydrophobic surfaces. These observations reveal that the extent and type of fibrinogen adsorption, as well as the propensity of adsorbed fibrinogen to bind platelets, may be modulated by careful selection of surface chemistry.

  1. Fibrinogen: A Marker in Predicting Diabetic Foot Ulcer Severity

    PubMed Central

    Li, X. H.; Guan, L. Y.; Lin, H. Y.; Wang, S. H.; Cao, Y. Q.; Jiang, X. Y.

    2016-01-01

    Aims. To examine whether fibrinogen levels are a valuable biomarker for assessing disease severity and monitoring disease progression in patients with diabetic foot ulcer (DFU). Methods. A retrospective study was designed to examine the utility of fibrinogen in estimating disease severity in patients with DFU admitted to our hospital between January 2015 and January 2016. In total, 152 patients with DFU were enrolled in the study group, and 52 age and gender matched people with diabetes but no DFU were included as the control group. DFU severity was assessed using Wagner criteria. Results. Patients with DFU were divided into 2 subgroups based on the Wagner criteria. Mean fibrinogen values were significantly higher in patients with DFU grade ≧ 3 compared to those with DFU grades 1-2 (5.23 ± 1.37 g/L versus 3.61 ± 1.04 g/L). Using ROC statistic, a cut-off value of 5.13 g/L indicated the possible amputation with a sensitivity of 81.8% and a specificity of 78.9% (positive predictive value [PPV] 78.6%, negative predictive value [89.0%]). Fibrinogen values were found to be correlated with CRP levels, neutrophil, and WBC count. Conclusions. Fibrinogen levels might be a valuable tool for assessing the disease severity and monitoring the disease progression in patients with DFU. PMID:28044140

  2. [Molecular biology of haemostasis: fibrinogen, factor XIII].

    PubMed

    Meyer, M

    2004-05-01

    Genetic defects of fibrinogen are caused by a broad spectrum of mutations in one of the three structural genes FGA, FGB and FGG. They result in complete or partial lack of plasma fibrinogen (a- or hypofibrinogenaemia) or in structural abnormalities affecting protein function (dysfibrinogenaemia). In contrast to afibrinogenaemia mainly caused by nonsense, frameshift, and splice site mutations resulting in substantially truncated polypeptide chains (mainly Aalpha), in hypo- and dysfibrinogenaemias missense mutations lead to the exchange of single amino acids as dominating underlying defect. In the cases with quantitative disorders, bleeding with various degrees of severity is generally observed. Dysfibrinogenaemia is associated with both bleeding or thrombosis or even a combination of haemorrhagic and thromboembolic symptoms. About one half of the dysfibrinogenaemic cases is clinically asymptomatic. The plasmatic factor XIII (FXIII) is a heterotetramer composed of two A and two B subunits encoded by two different genes. FXIII deficiency is associated with bleeding, wound dehiscence and recurrent spontaneous abortions. The most frequent form is caused by defects in the A subunit with a broad spectrum of underlying mutations. Defects of the B subunit are very rare and were molecularly elucidated in only a few cases.

  3. Low arginine plasma levels in patients after thoracoabdominal aortic surgery.

    PubMed

    Nijveldt, R J; Prins, H A; Siroen, M P; Rauwerda, J A; Teerlink, T; van Leeuwen, P A

    2000-08-01

    Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. Six patients with thoracoabdominal aortic aneurysm were included in this study. University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. Six patients undergoing thoracoabdominal aortic surgery. Plasma levels of arginine were measured by high-performance liquid chromatography. Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.

  4. Venous ulceration, fibrinogen and fibrinolysis.

    PubMed Central

    Leach, R. D.

    1984-01-01

    The effect of long and short-term venous hypertension upon lymph fibrinogen concentrations was studied in an attempt to explain the peri-capillary deposition of fibrin reported in patients with post-phlebitic syndromes. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of rats and human volunteers was also studied. Both long- and short-term venous hypertension were found to increase fibrinogen transport across the interstitial space by more than 600%. Not only was there evidence of fibrinolytic activity in the lymph but after long-term venous hypertension alpha 2 antiplasmin activity was also detectable. Skin biopsies from the venous hypertensive ankles showed deposition of interstitial fibrin. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of the rat was found to be delayed if the rats were given epsilon amino caproic acid but it could not be increased with stanozolol. In human subjects it was found that patients with lipodermatosclerosis had delayed clot clearance and retarded blood fibrinolytic activity when compared with normal volunteers and patients with uncomplicated varicose veins. The principle cause why tall men are more subject to ulcers than short men, Dr Young conceived to be then length of the column of blood in their veins; which by its pressure, renders the legs less able to recover when hurt by any violence. Images Fig. 1 Fig. 2 Fig. 5 PMID:6742738

  5. Changes in the fibrinogen-fibrin system following a 20-hour exposure of rabbits to a magnetic field

    NASA Technical Reports Server (NTRS)

    Matskevichene, V. B.; Vitenson, T. M.

    1974-01-01

    Prolonged exposure of animals to a constant magnetic field resulted in a sharp increase in the amount of fibrinogen. The addition of EACA to the plasma of experimental rabbits as well as protamine sulfate caused an additional increase in the amount of fibrinogen. A 20-hour exposure was accompanied by phenomena of paralysis of the pelvic limbs and death of some of the animals.

  6. Changes in the fibrinogen-fibrin system following a 20-hour exposure of rabbits to a magnetic field

    NASA Technical Reports Server (NTRS)

    Matskevichene, V. B.; Vitenson, T. M.

    1974-01-01

    Prolonged exposure of animals to a constant magnetic field resulted in a sharp increase in the amount of fibrinogen. The addition of EACA to the plasma of experimental rabbits as well as protamine sulfate caused an additional increase in the amount of fibrinogen. A 20-hour exposure was accompanied by phenomena of paralysis of the pelvic limbs and death of some of the animals.

  7. The relationship between levels of plasma-soluble urokinase plasminogen activator receptor (suPAR) and presence of migraine attack and aura.

    PubMed

    Yılmaz, Nigar; Yılmaz, Mustafa; Sirin, Burcu; Yılmaztekin, Sureyya; Kutlu, Gülnihal

    2017-10-01

    Migraine is one of the most common types of pain associated with sterile inflammatory conditions. Soluble urokinase plasminogen activator receptor (suPAR) is a potential novel inflammatory marker. We aim to determine the association between serum values of suPAR, procalcitonin, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) and migraine disease characteristics. The study involved a total of 60 migraine patients (33 patients in the interictal period, 27 patients in the attack period) and 30 healthy individuals. The serum values of suPAR were found to be significantly higher in migraine patients in the attack period than in migraine patients in the interictal period, and in healthy individuals (p < .01 for both). In addition, levels of suPAR were determined to be higher in migraine with aura patients than in migraine without aura patients. When we subdivided migraine patients according to frequency of attack (attacks/month), significant differences were found between the suPAR and procalcitonin levels (measured during the attack period) of those in the frequent-attack group (4-5 or more) versus those in the less frequent attack group (less than 4). Serum levels of procalcitonin were shown to be significantly higher in migraine patients during the attack period compared with migraine patients in the interictal period and in control subjects (p = .001 for both). Significant differences were found between plasma levels of fibrinogen in migraine patients versus control subjects (p < .01). No statistically significant difference was found between levels of hs-CRP in migraine patients versus the control group. These findings may show that presenting a high level of suPAR in migraine patients with attack and aura results to predisposition to occurring on the symptoms and that high levels of suPAR, procalcitonin and fibrinogen in patients with migraine result in neurogenic inflammation during migraine headaches.

  8. Plasma levels of acylated ghrelin in patients with functional dyspepsia

    PubMed Central

    Kim, Yeon Soo; Lee, Joon Seong; Lee, Tae Hee; Cho, Joo Young; Kim, Jin Oh; Kim, Wan Jung; Kim, Hyun Gun; Jeon, Seong Ran; Jeong, Hoe Su

    2012-01-01

    AIM: To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia. METHODS: Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study. The functional dyspepsia patients were each diagnosed based on the Rome III criteria. Eligible patients completed a questionnaire concerning the severity of 10 symptoms. Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal. RESULTS: There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia. However, in patients with functional dyspepsia, there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r = -0.427, P = 0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r = 0.428, P =0.047). Additionally, there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r = -0.522, P = 0.013). Interestingly, two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal. CONCLUSION: Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia. PMID:22611317

  9. Quantitative determination of fibrinogen of patients with coronary heart diseases through piezoelectric agglutination sensor.

    PubMed

    Chen, Qinghai; Hua, Xing; Fu, Weiling; Liu, Dongbo; Chen, Ming; Cai, Guoru

    2010-01-01

    Fibrinogen can transform fibrin through an agglutination reaction, finally forming fibrin polymer with grid structure. The density and viscosity of the reaction system changes drastically during the course of agglutination. In this research, we apply an independently-developed piezoelectric agglutination sensor to detect the fibrinogen agglutination reaction in patients with coronary heart diseases. The terminal judgment method of determining plasma agglutination reaction through piezoelectric agglutination sensor was established. In addition, the standard curve between plasma agglutination time and fibrinogen concentration was established to determinate fibrinogen content quantitatively. The results indicate the close correlation between the STAGO paramagnetic particle method and the method of piezoelectric agglutination sensor for the detection of Fibrinogen. The correlation coefficient was 0.91 (γ = 0.91). The determination can be completed within 10 minutes. The fibrinogen concentration in the coronary heart disease group was significantly higher than that of the healthy control group (P < 0.05). The results reveal that high fibrinogen concentration is closely correlated to the incurrence, development and prognosis of coronary heart diseases. Compared with other traditional methods, the method of piezoelectric agglutination sensor has some merits such as operation convenience, small size, low cost, quick detecting, good precision and the common reacting agents with paramagnetic particle method.

  10. Molecular basis for fibrinogen Dusart (A alpha 554 Arg-->Cys) and its association with abnormal fibrin polymerization and thrombophilia.

    PubMed Central

    Koopman, J; Haverkate, F; Grimbergen, J; Lord, S T; Mosesson, M W; DiOrio, J P; Siebenlist, K S; Legrand, C; Soria, J; Soria, C

    1993-01-01

    The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals. Images PMID:8473507

  11. Novel fibrinogen mutation (gamma 313 Ser-->Asn) associated with hypofibrinogenemia in two unrelated families.

    PubMed

    Meyer, Michael; Bergmann, Frauke; Brennan, Stephen O

    2006-01-01

    Congenital hypofibrinogenemia is a rare disorder caused by a number of different mutations in the fibrinogen genes. The aim of the study was the elucidation of molecular defects in two unrelated families with hypofibrinogenemia. DNA samples from the patients were screened for mutations in the fibrinogen genes by direct sequencing of polymerase chain reaction-amplified gene segments. Isolated plasma fibrinogen was studied by sodium dodecyl sulfate electrophoresis and electrospray ionization mass spectrometry in order to detect variant polypeptides. Fibrin polymerization was analyzed both in plasma and using purified fibrinogen samples. A novel mutation in the FGG gene (G7590A) was found in all patients from the two families with hypofibrinogenemia. This mutation causes the amino acid exchange 313 Ser-->Asn in the gamma chain. When plasma fibrinogen from a heterozygous individual was analyzed for the presence of variant gamma chains by reverse-phase high-performance liquid chromatography and electrospray ionization mass spectrometry, only normal gamma chains could be detected. The molecular defect affecting an evolutionary highly conserved amino acid residue in human fibrinogen interferes with plasma expression of the variant molecules and is causative for the observed hypofibrinogenemic phenotype.

  12. Recombinant human fibrinogen and sulfation of the. gamma. prime chain

    SciTech Connect

    Farrell, D.H.; Huang, S.; Chung, D.W.; Davie, E.W. ); Mulvihill, E.R. )

    1991-10-01

    Human fibrinogen and the homodimeric {gamma}{prime}-chain-containing variant have been expressed in BHK cells using cDNAs coding for the {alpha},{beta}, and {gamma} (or {gamma}{prime}) chains. The fibrinogens were secreted at levels greater than 4 {mu}g (mg of total cell protein){sup {minus}1}day{sup {minus}1} and were biologically active in clotting assays. Recombinant fibrinogen containing the {gamma}' chain incorporated {sup 35}SO{sub 4} into its chains during biosynthesis, while no incorporation occurred in the protein containing the {gamma} chain. The identity of the sulfated {gamma}{prime} chain was verified by its ability to form dimers during clotting. In addition, carboxypeptidase {Upsilon} digestion of the recombinant fibrinogen containing the {gamma}{prime} chain released 96% of the {sup 35}S label from the sulfated chain, and the radioactive material was identified as tyrosine O-sulfate. These results clarify previous findings of the sulfation of tyrosine in human fibrinogen.

  13. Recombinant fibrinogen reveals the differential roles of α- and γ-chain cross-linking and molecular heterogeneity in fibrin clot strain-stiffening.

    PubMed

    Piechocka, I K; Kurniawan, N A; Grimbergen, J; Koopman, J; Koenderink, G H

    2017-05-01

    Essentials Fibrinogen circulates in human plasma as a complex mixture of heterogeneous molecular variants. We measured strain-stiffening of recombinantly produced fibrinogen upon clotting. Factor XIII and molecular heterogeneity alter clot elasticity at the protofibril and fiber level. This highlights the hitherto unknown role of molecular composition in fibrin clot mechanics. Background Fibrin plays a crucial role in haemostasis and wound healing by forming strain-stiffening fibrous networks that reinforce blood clots. The molecular origin of fibrin's strain-stiffening behavior remains poorly understood, primarily because plasma fibrinogen is a complex mixture of heterogeneous molecular variants and is often contaminated by plasma factors that affect clot properties. Objectives and methods To facilitate mechanistic dissection of fibrin nonlinear elasticity, we produced a homogeneous recombinant fibrinogen corresponding to the main variant in human plasma, termed rFib610. We characterized the structure of rFib610 clots using turbidimetry, microscopy and X-ray scattering. We used rheology to measure the strain-stiffening behavior of the clots and determined the fiber properties by modeling the clots as semi-flexible polymer networks. Results We show that addition of FXIII to rFib610 clots causes a dose-dependent stiffness increase at small deformations and renders the strain-stiffening response reversible. We find that γ-chain cross-linking contributes to clot elasticity by changing the force-extension behavior of the protofibrils, whereas α-chain cross-linking stiffens the fibers, as a consequence of tighter coupling between the constituent protofibrils. Interestingly, rFib610 protofibrils have a 25% larger bending rigidity than plasma-purified fibrin protofibrils and a delayed strain-stiffening, indicating that molecular heterogeneity influences clot mechanics at the protofibril scale. Conclusions Fibrinogen molecular heterogeneity and FXIII affect the

  14. Plasma vasopressin levels in induced migraine attacks.

    PubMed

    Peatfield, R C; Hampton, K K; Grant, P J

    1988-03-01

    Vasopressin (aVP) at low concentrations functions as an antidiuretic hormone and has vasoconstrictive effects. To investigate the possible role of aVP in the pathogenesis of migraine, six patients with a history of induced migraine were given 100 g chocolate, and blood samples for plasma aVP were taken before ingestion and every hour for 4 h. In one patient who presented with severe headache and nausea the base-line plasma aVP concentration was 15.2 pg/ml; it fell to 3.2 pg/ml at 2 h before rising to 10 pg/ml at 3 h and 4 h as the symptoms worsened. In the five patients with moderate or no headache plasma aVP concentrations remained in the normal range (less than 3 pg/ml) throughout. The results suggest that aVP does not have a role in the aetiology of migraine. The possibility exists that during severe attacks of nausea there is release of aVP, which may be responsible for the facial pallor, antidiuresis, and coagulation abnormalities occasionally observed in migraine.

  15. Fibrinogen and prothrombin complex concentrate in trauma coagulopathy.

    PubMed

    Hannon, Matthew; Quail, Jacob; Johnson, Matthew; Pugliese, Cara; Chen, Kejian; Shorter, Heidi; Riffenburgh, Robert; Jackson, Ronald

    2015-06-15

    Coagulopathy after injury contributes to hemorrhage and death. Treatment with specific coagulation factors could decrease hemorrhage and mortality. Our aim was to compare fibrinogen and prothrombin complex concentrate (PCC) in a rabbit model of hemorrhagic shock. New Zealand white rabbits were anesthetized. Blood was withdrawn to a mean arterial pressure (MAP) of 30-40 mm Hg for 30 min. Animals were resuscitated with lactated Ringer to a MAP of 50-60 mm Hg and randomized to receive 100 mg/kg of fibrinogen, PCC 25 IU/kg, or lactated Ringer. A liver injury was created. A MAP of 50-60 mm Hg was maintained for 60 min. The primary outcome was blood loss, and secondary outcomes were fluid administered and coagulopathy as measured by plasma-based tests. There were eight animals in each group. Median blood loss was significantly higher in the fibrinogen group, at 122 mL (95% confidence interval [CI], 75-194), when compared with that in the control group, 35 mL (95% CI, 23-46; P value = 0.001), and the PCC group, 26 mL (95% CI, 4-54; P value = 0.002). Resuscitation fluid requirement was highest in the fibrinogen group, at 374 mL (95% CI, 274-519), and lowest in the PCC group, at 238 mL (95% CI, 212-309) (P = 0.01). Plasma-based coagulation tests were not different among groups. In a rabbit model, PCC did not have a significant effect on blood loss. Fibrinogen increased blood loss and fluid requirements. Published by Elsevier Inc.

  16. Purification of fibrinogen and virus removal using preparative electrophoresis.

    PubMed

    Gilbert, A; Evtushenko, M; Nair, H

    2001-01-01

    The Gradiflow is a novel, scalable preparative electrophoresis technique that uses the dual characteristics of size and charge to isolate target macro- and micromolecules from complex biological solutions. It does this with high resolution and in rapid time. The mild buffers are used to assist in retaining biological activity of the isolated protein. Gradiflow technology employs a sandwich of three polyacrylamide membranes configured to allow passage of macromolecules ranging in size from 10 kDa to 1,500 kDa. Fibrinogen was isolated from cryoprecipitate 1 using a single phase process. This separation was achieved within three hours with yields of 85%. Purified fibrinogen was then characterized using biophysical characterization of fibrin clot structure and compared with clots derived from a commercially available product and human plasma. Significantly, clots developed from Gradiflow fibrinogen had characteristics closer to human plasma. Viral removal characteristics of the Gradiflow were investigated by spiking the source material (cryoprecipitate 1) with canine parvovirus and testing for its presence in the isolated fibrinogen using PCR. Parvo removal was found to be greater than 4 logs and was achieved during the purification process. The Gradiflow offers the advantage of large-scale separation of macromolecules and provides a new approach to fibrinogen separation that is quite distinct from other present-day technologies. The technology is capable of isolating protein with high purity, recovery, and functionality in combination with the removal of viruses during the purification. Furthermore, it is capable of integrating into present production systems, significantly improving yield and functionality of target molecules.

  17. Low plasma progranulin levels in children with autism.

    PubMed

    Al-Ayadhi, Laila Y; Mostafa, Gehan A

    2011-09-05

    Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

  18. Elevated plasma interleukin-37 levels in systemic lupus erythematosus patients.

    PubMed

    Wu, G-C; Li, H-M; Wang, J-B; Leng, R-X; Wang, D-G; Ye, D-Q

    2016-10-01

    This study aims to evaluate the plasma interleukin (IL)-37 levels in systemic lupus erythematosus (SLE) patients, as well as its association with major clinical and laboratory features. Ninety consecutively selected SLE patients and 78 community-based healthy controls were recruited. Plasma IL-37 levels were detected by enzyme-linked immunosorbent assay (ELISA). The major clinical and laboratory data of SLE patients were also recorded. The results showed that IL-37 level was significantly higher in the plasma of patients with SLE compared with controls (p = 0.028). The correlation of plasma IL-37 levels with major clinical and laboratory data of SLE patients was also analyzed, and the results showed that anti-Sm and anti-RNP were negatively associated with plasma IL-37 levels of SLE patients, while C3 was positively associated with plasma IL-37 levels of SLE patients. No significant associations of IL-37 with other clinical and laboratory parameters were observed (all p > 0.05). In conclusion, elevated plasma IL-37 level and its associations with anti-Sm, anti-RNP and C3 in SLE patients suggest that IL-37 may be implicated in this disease. © The Author(s) 2016.

  19. Adsorption and functionality of fibrinogen on triblock copolymer-coated surfaces

    NASA Astrophysics Data System (ADS)

    O'Connor, Stephen Moss

    To assess the influence of the surface microenvironment on the adsorption and biologic activity of fibrinogen, a series of poly(ethylene oxide)/poly(propylene oxide) triblock copolymers were adsorbed to solid, hydrophobic polystyrene-divinylbenzene beads. The copolymers, which were of the form PEOsb{b}PPOsb{a}PEOsb{b}, varied in their hydrophile/lipophile balances (HLB) due only to differences in their PEO chain length (5 to 129 EO units) as the hydrophobic PPO core segment was of fixed length (56 or 69 PO units). The surface coverage of copolymers was determined first and after exposing the beads to fibrinogen or to human plasma, the total amount of protein adsorbed to their surface was measured. The functionality of fibrinogen bound to copolymer-modified beads was assessed in terms of fibrin clot formation and by the adherence of macrophages (THP-1 tumor cells). Enzymatic processing was used to probe the surface orientation of fibrinogen. The copolymers appear to adsorb in an expanded fashion, a conclusion supported by surface pressure-area isotherms of the copolymers spread at the air-water interface. As compared to copolymer-free surfaces, protein adsorption decreases by up to 90% as the PEO chain length of the copolymers increases. The copolymer coatings appear to lower fibrinogen adsorption by limiting the available surface area. On surfaces coated with the hydrophobic versions of the copolymers, the biologic assays demonstrate that fibrinogen is as reactive/coagulable as for surfaces with saturated coverages of fibrin despite that these copolymer-coated surfaces have 60% less fibrinogen adsorbed to them. When adsorbed at the same low surface concentration in the absence of copolymer, fibrinogen is not active. Enzymatic processing of bound fibrinogen suggests that the presence of the copolymers promote the adsorption of the protein in end-on fashion. It is proposed here, that when adsorbed end-on, fibrinogen is functional because its reactive sites are

  20. Effect of potato ethanol residue on rat plasma cholesterol levels.

    PubMed

    Hashimoto, Naoto; Shinomiya, Noriyuki; Saito, Katsuichi; Noda, Takahiro; Han, Kyu-Ho; Fukushima, Michihiro

    2013-01-01

    We investigated the cholesterol-lowering effect of a potato ethanol residue (PER). The plasma cholesterol levels excluding high-density lipoprotein cholesterol were lower in the rats given a PER-containing diet for 6 weeks than in the control group, whereas the fecal cholesterol levels were higher. These results suggest that PER partially reduced plasma cholesterol levels via excretion of cholesterol into the feces.

  1. Fibrinogen and red blood cells in venous thrombosis.

    PubMed

    Aleman, Maria M; Walton, Bethany L; Byrnes, James R; Wolberg, Alisa S

    2014-05-01

    Deep vein thrombosis and pulmonary embolism, collectively termed venous thromboembolism (VTE), affect over 1 million Americans each year. VTE is triggered by inflammation and blood stasis leading to the formation of thrombi rich in fibrin and red blood cells (RBCs). However, little is known about mechanisms regulating fibrin and RBC incorporation into venous thrombi, or how these components mediate thrombus size or resolution. Both elevated circulating fibrinogen (hyperfibrinogenemia) and abnormal fibrin(ogen) structure and function, including increased fibrin network density and resistance to fibrinolysis, have been observed in plasmas from patients with VTE. Abnormalities in RBC number and/or function have also been associated with VTE risk. RBC contributions to VTE are thought to stem from their effects on blood viscosity and margination of platelets to the vessel wall. More recent studies suggest RBCs also express phosphatidylserine, support thrombin generation, and decrease fibrinolysis. RBC interactions with fibrin(ogen) and cells, including platelets and endothelial cells, may also promote thrombus formation. The contributions of fibrin(ogen) and RBCs to the pathophysiology of VTE warrants further investigation.

  2. Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study.

    PubMed

    Woodward, Mark; Tunstall-Pedoe, Hugh; Rumley, Ann; Lowe, Gordon D O

    2009-08-01

    Plasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30-74 years, initially free of CVD. After follow-up for a median of 19.2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio-economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1.09 (1.02, 1.16) for men and 1.10 (1.02, 1.19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1.3% and 3.2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost-effective.

  3. Thrombosis in Inherited Fibrinogen Disorders

    PubMed Central

    Korte, Wolfgang; Poon, Man-Chiu; Iorio, Alfonso; Makris, Michael

    2017-01-01

    Although inherited fibrinogen disorders (IFD) are primarily considered to be bleeding disorders, they are associated with a higher thrombotic complication risk than defects in other clotting factors. Managing IFD patients with thrombosis is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk which can be life-threatening. Due to the low prevalence of IFD, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. We searched the literature for cases of thrombosis among IFD patients and identified a total of 128 patient reports. In approximately half of the cases, thromboses were spontaneous, while in the others trauma, surgery, and parturition contributed to the risk. The true mechanism(s) of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant treatments have been used in the treatment or prevention of thrombosis, sometimes with concurrent fibrinogen replacement therapy. There is no definite evidence that fibrinogen supplementation increases the risk of thrombosis, and it may potentially be effective in the treatment and prevention of both thrombosis and hemorrhage in IFD patients. PMID:28503122

  4. A study on human serum albumin influence on glycation of fibrinogen

    SciTech Connect

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr

    2013-09-13

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

  5. Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in pre-eclamptic patients.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    2014-06-01

    Pre-eclampsia (PE) remains the leading cause of pregnancy-associated mortality and morbidity, urging the need for a better understanding of its aetiology and pathophysiological progression. A key characteristic of PE is a systemic, exaggerated, inflammatory condition involving abnormal cytokine levels in serum, altered immune cell phenotype and Th1/Th2-type immunological imbalance. However, it is unknown how this heightened inflammatory condition manifests. We previously reported increased expression of the lipopolysaccharide receptor, Toll-like receptor 4 (TLR4), on monocytes from PE patients compared with normotensive, pregnant patients (NP). This upregulation of TLR4 on PE monocytes was accompanied by a hyper-responsiveness to bacterial TLR4 ligands. To determine whether non-microbial, endogenous TLR4 ligands also activate monocytes from PE patients, we investigated the expression of host-derived TLR4 ligands and the response of monocytes to these endogenous ligands. Plasma levels of fibrinogen - but not fibronectin or heparan sulphate - were higher in PE patients than in NP. Exposure to fibrinogen was associated with significantly increased production of inflammatory cytokines by monocytes from PE patients. Interestingly, this effect was not observed with NP monocytes. Our findings suggest that the fibrinogen-TLR4 axis might play an important role in the atypical activation of monocytes observed in PE patients that may contribute to the exaggerated inflammatory condition.

  6. Novel Aalpha chain truncation (fibrinogen Perth) resulting in low expression and impaired fibrinogen polymerization.

    PubMed

    Homer, V M; Mullin, J L; Brennan, S O; Barr, A; George, P M

    2003-06-01

    A young woman with a history of menorrhagia and easy bruising presented with a functional fibrinogen concentration of 1.8 mg mL(-1), a gravimetric concentration of 3.3 mg mL(-1) and a prolonged thrombin clotting time of 32 s. Both reverse phase analysis and reducing SDS-PAGE revealed a normal profile of Aalpha, Bbeta, and gamma chains. However, non-reducing gels revealed a broadened 340-kDa band, while the 305-kDa band was normal, suggesting a C-terminal truncation of the Aalpha chain. DNA sequencing of all exons and intron boundaries revealed a single heterozygous cytosine deletion at nucleotide 4841 of the Aalpha gene predicting a frameshift and the incorporation of 23 new residues (LMKLPSSTLPQLEKHSQVSSHLC) before termination after residue 517. In agreement with a predicted mass decrease of 9953 Da, the measured mass of the Aalpha(Perth) chain was 56 242 Da, while that of the normal Aalpha(A) chain was 66 189 Da. Tryptic mapping of isolated Aalpha chains revealed a new [M + 2H] ion at 607 m z(-1), corresponding to the predicted penultimate peptide LPSSTLPQLEK. The variant chain was poorly incorporated into plasma fibrinogen at a ratio of Aalpha(Perth)/Aalpha(A) of 0.15 : 1, suggesting the Aalpha(Perth) chain might be out-competed by normal chains during molecular assembly in the hepatocyte. Despite the low expression, polymerization curves showed a decreased V(max) and final turbidity, suggesting the fibrinogen Perth clots are composed of thinner fibers. However, the fibrinolytic rate was very similar to that of the control.

  7. Zeolite Nanoparticles Inhibit Aβ-Fibrinogen Interaction and Formation of a Consequent Abnormal Structural Clot.

    PubMed

    Derakhshankhah, Hossein; Hajipour, Mohammad Javad; Barzegari, Ebrahim; Lotfabadi, Alireza; Ferdousi, Maryam; Saboury, Ali Akbar; Ng, Eng Poh; Raoufi, Mohammad; Awala, Hussein; Mintova, Svetlana; Dinarvand, Rassoul; Mahmoudi, Morteza

    2016-11-16

    EMT-type zeolite nanoparticles (EMT NPs) with particle size of 10-20 nm and external surface area of 200 m(2)/g have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD). To evaluate this hypothesis, the clot formation and degradation of Aβ-fibrinogen in the presence and absence of the EMT zeolite NPs were assessed. The results clearly showed that the delay in clot dissolution was significantly reduced in the presence of zeolite NPs. By formation of protein corona, the EMT NPs showed a negligible reduction in their inhibitory strength. Docking of small molecules (Aβ-fibrinogen) introduced a novel potential inhibitory candidate. The zeolite NPs showed similar inhibitory effects on binding of fibrinogen to both Aβ(25-35) and/or Aβ(1-42). This indicates that the inhibitory strength of these NPs is independent of Aβ sequence, and it is suggested that the zeolite NPs adsorb fibrinogen and specifically obstruct their Aβ binding sites. Therefore, the zeolite NPs can be the safe and effective inhibitors in preventing Aβ-fibrinogen interaction and consequent cognitive damage.

  8. Recurrence of the 'deep-intronic' FGG IVS6-320A>T mutation causing quantitative fibrinogen deficiency in the Italian population of Veneto.

    PubMed

    Platè, Manuela; Duga, Stefano; Castaman, Giancarlo; Rodeghiero, Francesco; Asselta, Rosanna

    2009-07-01

    Quantitative fibrinogen deficiency is a rare bleeding disorder characterized by abnormally low levels of fibrinogen in plasma, generally due to mutations in one of the three fibrinogen genes: FGA, FGB, and FGG, coding for A alpha, B beta, and gamma chain, respectively. Although the partial defect (hypofibrinogenemia) is due to mutations occurring in the heterozygous state, homozygosity or compound heterozygosity for the same genetic defects give rise to the more severe afibrinogenemia. Mutations responsible for these conditions are scattered throughout the three fibrinogen genes, with only few sites representing relative mutational hot spots. In this study, we report the identification of the FGG IVS6-320A>T mutation in an Italian hypofibrinogenemic patient from Veneto (a region of North-Eastern Italy). This 'deep-intronic' mutation, which would go unnoticed by using conventional mutational screening strategies was previously reported in an afibrinogenemic family from Vicenza (a province of Veneto). The geographic clustering of patients carrying the FGG IVS6-320A>T mutation and the results of haplotype analysis suggest the existence of a common founder. This information will be useful to direct future genetic screenings in patients coming from the same geographic area.

  9. Loss of Fibrinogen in Zebrafish Results in Symptoms Consistent with Human Hypofibrinogenemia

    PubMed Central

    Liu, Yang; Norris, Zachary G.; Shavit, Jordan A.

    2013-01-01

    Cessation of bleeding after trauma is a necessary evolutionary vertebrate adaption for survival. One of the major pathways regulating response to hemorrhage is the coagulation cascade, which ends with the cleavage of fibrinogen to form a stable clot. Patients with low or absent fibrinogen are at risk for bleeding. While much detailed information is known about fibrinogen regulation and function through studies of humans and mammalian models, bleeding risk in patients cannot always be accurately predicted purely based on fibrinogen levels, suggesting an influence of modifying factors and a need for additional genetic models. The zebrafish has orthologs to the three components of fibrinogen (fga, fgb, and fgg), but it hasn’t yet been shown that zebrafish fibrinogen functions to prevent bleeding in vivo. Here we show that zebrafish fibrinogen is incorporated into an induced thrombus, and deficiency results in hemorrhage. An Fgb-eGFP fusion protein is incorporated into a developing thrombus induced by laser injury, but causes bleeding in adult transgenic fish. Antisense morpholino knockdown results in intracranial and intramuscular hemorrhage at 3 days post fertilization. The observed phenotypes are consistent with symptoms exhibited by patients with hypo- and afibrinogenemia. These data demonstrate that zebrafish possess highly conserved orthologs of the fibrinogen chains, which function similarly to mammals through the formation of a fibrin clot. PMID:24098662

  10. Conformational dynamic of fibrinogen by dielectric spectroscopy

    NASA Astrophysics Data System (ADS)

    Berest, Vladimir P.; Gatash, Sergiy V.

    1999-12-01

    The information concerning the structural changes of fibrinogen molecule at temperatures form 4 to 52 degrees C has ben obtained by means of dielectric-spectroscopy method. Besides the known conformational transition II, under physiological conditions conformational transition at 20-22 degrees C has been observed in fibrinogen. This transition might be connected with structural transition in peripheral domain of fibrinogen. Revealed conformational transition, probably, determines the character of the temperature dependence of blood platelet aggregation.

  11. DNA methylation profiling of the fibrinogen gene landscape in human cells and during mouse and zebrafish development.

    PubMed

    Vorjohann, Silja; Pitetti, Jean-Luc; Nef, Serge; Gonelle-Gispert, Carmen; Buhler, Leo; Fish, Richard J; Neerman-Arbez, Marguerite

    2013-01-01

    The fibrinogen genes FGA, FGB and FGG show coordinated expression in hepatocytes. Understanding the underlying transcriptional regulation may elucidate how their tissue-specific expression is maintained and explain the high variability in fibrinogen blood levels. DNA methylation of CpG-poor gene promoters is dynamic with low methylation correlating with tissue-specific gene expression but its direct effect on gene regulation as well as implications of non-promoter CpG methylation are not clear. Here we compared methylation of CpG sites throughout the fibrinogen gene cluster in human cells and mouse and zebrafish tissues. We observed low DNA methylation of the CpG-poor fibrinogen promoters and of additional regulatory elements (the liver enhancers CNC12 and PFE2) in fibrinogen-expressing samples. In a gene reporter assay, CpG-methylation in the FGA promoter reduced promoter activity, suggesting a repressive function for DNA methylation in the fibrinogen locus. In mouse and zebrafish livers we measured reductions in DNA methylation around fibrinogen genes during development that were preceded by increased fibrinogen expression and tri-methylation of Histone3 lysine4 (H3K4me3) in fibrinogen promoters. Our data support a model where changes in hepatic transcription factor expression and histone modification provide the switch for increased fibrinogen gene expression in the developing liver which is followed by reduction of CpG methylation.

  12. Chemotherapy and plasma adipokines level in patients with colorectal cancer.

    PubMed

    Słomian, Grzegorz; Świętochowska, Elżbieta; Nowak, Grzegorz; Pawlas, Krystyna; Żelazko, Aleksandra; Nowak, Przemysław

    2017-04-12

    Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC). Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD). We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment. We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.

  13. Plasma obestatin levels in normal weight, obese and anorectic women.

    PubMed

    Zamrazilová, H; Hainer, V; Sedlácková, D; Papezová, H; Kunesová, M; Bellisle, F; Hill, M; Nedvídková, J

    2008-01-01

    Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies.

  14. Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients.

    PubMed

    Iglesias García, Celso; Iglesias Alonso, Ana; Bobes, Julio

    2017-08-22

    There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen.

    PubMed

    Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J

    2011-04-01

    Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

  16. Treatment of congenital fibrinogen deficiency: overview and recent findings.

    PubMed

    Tziomalos, Konstantinos; Vakalopoulou, Sofia; Perifanis, Vassilios; Garipidou, Vassilia

    2009-01-01

    Afibrinogenemia is a rare bleeding disorder with an estimated prevalence of 1:1,000,000. It is an autosomal recessive disease resulting from mutations in any of the 3 genes that encode the 3 polypeptide chains of fibrinogen and are located on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor trauma and excessive bleeding during interventional procedures are the principal manifestations. We review the management of afibrinogenemia. Replacement therapy is the mainstay of treatment of bleeding episodes in these patients and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments that should be used only when fibrinogen concentrate is not available. Secondary prophylactic treatment may be considered after life-threatening bleeding whereas primary prophylactic treatment is not currently recommended. We also discuss alternative treatment options and the management of surgery, pregnancy and thrombosis in these patients. The development of new tests to identify higher risk patients and of safer replacement therapy will improve the management of afibrinogenemia in the future.

  17. Treatment of congenital fibrinogen deficiency: overview and recent findings

    PubMed Central

    Tziomalos, Konstantinos; Vakalopoulou, Sofia; Perifanis, Vassilios; Garipidou, Vassilia

    2009-01-01

    Afibrinogenemia is a rare bleeding disorder with an estimated prevalence of 1:1,000,000. It is an autosomal recessive disease resulting from mutations in any of the 3 genes that encode the 3 polypeptide chains of fibrinogen and are located on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor trauma and excessive bleeding during interventional procedures are the principal manifestations. We review the management of afibrinogenemia. Replacement therapy is the mainstay of treatment of bleeding episodes in these patients and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments that should be used only when fibrinogen concentrate is not available. Secondary prophylactic treatment may be considered after life-threatening bleeding whereas primary prophylactic treatment is not currently recommended. We also discuss alternative treatment options and the management of surgery, pregnancy and thrombosis in these patients. The development of new tests to identify higher risk patients and of safer replacement therapy will improve the management of afibrinogenemia in the future. PMID:19851522

  18. Excess nicotinamide increases plasma serotonin and histamine levels.

    PubMed

    Tian, Yan-Jie; Li, Da; Ma, Qiang; Gu, Xin-Yi; Guo, Ming; Lun, Yong-Zhi; Sun, Wu-Ping; Wang, Xin-Yuan; Cao, Yu; Zhou, Shi-Sheng

    2013-02-25

    Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).

  19. Clinical significance of plasma metastin level in pancreatic cancer patients.

    PubMed

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  20. [Relationship between clozapine plasma levels and withdrawal symptoms].

    PubMed

    Berecz, R; de la Rubia Martínez, A; Norberto Gamero, M J; Gutiérrez Casares, J R; Glaub, T; Degrell, I; Llerena, A

    2002-01-01

    Discontinuation of clozapine and an attempt to change his medication to sertindol has led to serious psychotic and somatic symptoms in an schizophrenic patient treated with clozapine for five years, however after readministration of clozapine these symptoms rapidly disappeared. To further analyse the case we have developed an HPLC method for the measurement of plasma levels of clozapine and its main metabolite N-desmethyl clozapine in order to monitor the plasma levels of clozapine and to correlate with the clinical symptoms. The present results confirmed that after discontinuation of clozapine no measurable amount of drug or its main metabolite were present in the plasma of the patient. The correlation between the plasma levels of clozapine and the changes in the clinical state of the patient confirmed that the patient's severe psychotic and somatic symptoms were the result of discontinuation of clozapine treatment. The clozapine plasma concentration of the patient reported here was low (100 ng/ml) compared to the generally accepted plasma levels for antipsychotic action of clozapine (350 ng/ml), however the somatic and psychotic clozapine withdrawal symptoms rapidly and completely disappeared.

  1. Pharmacological and genetic depletion of fibrinogen protects from kidney fibrosis

    PubMed Central

    Craciun, Florin L.; Ajay, Amrendra K.; Hoffmann, Dana; Saikumar, Janani; Fabian, Steven L.; Bijol, Vanesa; Humphreys, Benjamin D.

    2014-01-01

    Fibrinogen (Fg) has been implicated in the pathogenesis of several fibrotic disorders by acting as a profibrotic ligand for a variety of cellular surface receptors and by modulating the provisional fibrin matrix formed after injury. We demonstrated increased renal Fg expression after unilateral ureteral obstruction and folic acid (FA) nephropathy in mice, respectively. Urinary Fg excretion was also increased in FA nephropathy. Using in vitro and in vivo approaches, our results suggested that IL-6 mediates STAT3 activation in kidney fibrosis and that phosphorylated (p)STAT3 binds to Fgα, Fgβ, and Fgγ promoters in the kidney to regulate their transcription. Genetically modified Fg heterozygous mice (∼75% of normal plasma Fg levels) exhibited only 3% kidney interstitial fibrosis and tubular atrophy after FA nephropathy compared with 24% for wild-type mice. Fibrinogenolysis through Ancrod administration after FA reduced interstitial fibrosis more than threefold compared with vehicle-treated control mice. Mechanistically, we show that Fg acts synergistically with transforming growth factor (TGF)-β1 to induce fibroblast proliferation and activates TGF-β1/pSMAD2 signaling. This study offers increased understanding of Fg expression and molecular interactions with TGF-β1 in the progression to kidney fibrosis and, importantly, indicates that fibrinogenolytics like Ancrod present a treatment opportunity for a yet intractable disease. PMID:25007874

  2. [Fibrinogen beta chain gene mutation contributes to one congenital afibrinogenemia].

    PubMed

    Xu, Xiu-cai; Zhou, Rong-fu; Wu, Jing-sheng; Fang, Yi; Wang, Xue-feng; Zhai, Zhi-min; Wang, Hong-li

    2005-03-01

    To identify the fibrinogen (Fg) gene mutations in a Chinese pedigree of congenital afibrinogenemia. The plasma Fg activity and protein of the proband and his family members were detected. Genomic DNA was isolated from the peripheral blood mononuclear cells. All the exons and exon-intron boundaries of fibrinogen gene were amplified by PCR and sequenced thereafter. Two mutations, 7972 del G in FGB and T2543A in FGG, were found in the proband. FGG2543 is a polymorphism site, which lead to the polymorphism of gamma144 I/K. The G deletion at base 7972 of FGB contributes to the frameshift mutation after amino acid 419, resulting in the truncated beta chain without the terminal 27 amino acids. The latter may contributes to the pathogenetic mechanisms in Chinese congenital afibrinogenemia patients. The G deletion at base 7972 of FGB is identified for the first time.

  3. A comparison of the fibrinogen receptor distribution on adherent platelets using both soluble fibrinogen and fibrinogen immobilized on gold beads.

    PubMed

    Estry, D W; Mattson, J C; Mahoney, G J; Oesterle, J R

    1991-04-01

    The distribution of fibrinogen receptors was determined on the surface of adherent platelets using both direct labeling with the ligand fibrinogen which was immobilized on gold particles (Fg-Au) and indirect immunogold (Ig-Au) labeling of bound soluble fibrinogen identified with a rabbit polyclonal anti-fibrinogen antibody. Two distinctly different patterns of labeling were obtained and appeared to depend on whether solid phase fibrinogen (Fg-Au) or soluble phase released fibrinogen were bound to the membrane receptor. The membrane-bound Fg-Au reorganized in patterns that closely mimicked the organization of the underlying cytoskeleton. In approximately 18% of the adherent platelets, Fg-Au was seen in channels or vesicle-like structures lying deep to the platelet surface suggesting internalization into the open canalicular system and/or endocytosis. The labeling pattern obtained when identifying the location of membrane-bound soluble released fibrinogen by Ig-Au was diffuse and lacked the organizational patterns characteristic of Fg-Au. Unlike the Fg-Au probe, early dendritic platelets were heavily labeled by the soluble phase fibrinogen using the Ig-Au technique. Although the label covered the entire exposed platelet membrane in fully spread platelets, labeling over the peripheral web was more dense than that over the intermediate or granulomere zone. The diffuse organization and heavier peripheral distributional pattern of the glycoprotein IIb-IIIa (GP IIb-IIIa) receptor in fixed, adherent platelets, was also seen with the GP IIb-IIIa receptor-specific antibody AP-2. The binding of both the Fg-Au and Ig-Au were inhibited using the tetrapeptide Arg-Gly-Asp-Ser (RGDS) (93% and 98% inhibition, respectively), AP-2 (98% and 97%, respectively) and platelets from patients with Glanzmann's thrombasthenia (GT) (99% and 98%, respectively). The data presented provides the first report that receptor reorganization, following binding of fibrinogen, appears to be related to

  4. Insufficient fibrinogen response following free flap surgery is associated with bleeding complications

    PubMed Central

    Kolbenschlag, Jonas; Diehm, Yannick; Daigeler, Adrien; Kampa, David; Fischer, Sebastian; Kapalschinski, Nicolai; Goertz, Ole; Lehnhardt, Marcus

    2016-01-01

    Background: Microvascular tissue transfer has become a safe and reliable tool in the reconstructive armamentarium, yielding high success rates. However, little is known about the changes in coagulation after free tissue transfer and their potential impact on morbidity. Methods: Fibrinogen concentration and platelet count among other values were available and assessed in 139 undergoing free tissue transfer before, immediately after, and 1–3 as well as 8–11 days after surgery. In patients undergoing urgent revision for either bleeding or microvascular thrombosis, blood samples were drawn directly before re-exploration. Results: In the patients without any surgical revision and in those with thrombosis of the microvascular pedicle, both fibrinogen concentration and platelet count increased significantly during the early and late post-operative window. Patients that developed bleeding necessitating re-exploration showed an inadequate increase in fibrinogen levels, resulting in significantly lower concentrations compared to the other two groups. There were no significant differences in platelet count or PTT between these groups. Conclusion: Free flap surgery induces acute and subacute changes in coagulation, comparable to other major surgeries and severe injuries. This leads to an increase in platelet count and fibrinogen over the post-operative course. Patients that developed bleeding requiring surgical re-exploration showed an insufficient increase in fibrinogen, resulting in significantly lower fibrinogen levels. Therefore, monitoring and correction of fibrinogen levels might aid in preventing or treating bleeding complications following free flap surgery. PMID:27975041

  5. Study of plasma adrenomedullin level in normal pregnancy and preclampsia.

    PubMed

    Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I

    2008-02-06

    The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.

  6. Study of Plasma Adrenomedullin Level In Normal Pregnancy and Preclampsia

    PubMed Central

    Senna, Azza Abo; Zedan, Magda; Abd El Salam, Gamal E.; El Mashad, Ashraf I.

    2008-01-01

    Aim The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. Subjects and Methods In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Results Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Conclusion Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy. PMID:18382699

  7. Mechanisms of fibrinogen adsorption at solid substrates.

    PubMed

    Adamczyk, Zbigniew; Bratek-Skicki, Anna; Żeliszewska, Paulina; Wasilewska, Monika

    2014-01-01

    The aim of this work was to critically review recent results pertinent to fibrinogen adsorption at solid/electrolyte interfaces with the emphasis focused on a quantitative analysis of these processes in terms of the electrostatic interactions. Accordingly, in the first part, the primary chemical structure of fibrinogen is analyzed. Physicochemical data pertinent to the bulk properties derived from hydrodynamic, dynamic light scattering and micro-electrophoretic measurements aided by theoretical modeling are discussed. Possible conformations and the effective charge distribution over the fibrinogen molecule for various pH an ionic strength are defined, especially the semi-collapsed conformation prevailing at physiological conditions. Adsorption kinetics of fibrinogen at hydrophilic and hydrophobic (polymer modified) substrates determined by various techniques is described. Adsorption at polymeric carrier particles, pertinent to immunological assays, studied in terms of electrokinetic and concentration depletion methods, are also considered. The reversibility of adsorption, fibrinogen molecule orientations and maximum coverages are thoroughly discussed. The stability of fibrinogen monolayers formed at these carrier particles in respect to pH and ionic strength cyclic changes is also discussed. In the final section interactions and deposition of model colloid particles on fibrinogen monolayers are analyzed which allows one to derive valuable information about molecule orientations. Based on the physicochemical data, adsorption kinetics and colloid particle deposition measurements, probable adsorption mechanisms of fibrinogen on solid/electrolyte interfaces are defined.

  8. Over 50 Years of Fibrinogen Concentrate

    PubMed Central

    Hochleitner, Gerald; Wendt, Michael; Teruya, Alexandre; Spahn, Donat R.

    2015-01-01

    March 2013 represented the 50th anniversary of the first license granted for a fibrinogen concentrate. In this review, we look at the history of bleeding management that led to the development of fibrinogen concentrate, discuss its current use, and consider future developments for this product. PMID:26294722

  9. Ozone-induced oxidative modification of fibrinogen: role of the D regions.

    PubMed

    Rosenfeld, Mark A; Shchegolikhin, Alexander N; Bychkova, Anna V; Leonova, Vera B; Biryukova, Marina I; Kostanova, Elizaveta A

    2014-12-01

    Native fibrinogen is a key blood plasma protein whose main function is to maintain hemostasis by virtue of producing cross-linked fibrin clots under the influence of thrombin and fibrin-stabilizing factor (FXIIIa). The aim of this study was to investigate mechanisms of impairment of both the molecular structure and the spatial organization of fibrinogen under ozone-induced oxidation. FTIR analysis showed that ozone treatment of the whole fibrinogen molecule results in the growth of hydroxyl, carbonyl, and carboxyl group content. A similar analysis of fibrinogen D and E fragments isolated from the oxidized protein also revealed transformation of distinct important functional groups. In particular, a remarkable decay of N-H groups within the peptide backbone was observed along with a lowering of the content of C-H groups belonging to either the aromatic moieties or the aliphatic chain CH2 and CH3 units. The model experiments performed showed that the rather unexpected decay of the aliphatic CH units might be caused by the action of hydroxyl radicals, these being produced in the water solution from ozone. The observed dissimilarities in the shapes of amide I bands of the fibrinogen D and E fragments before and after ozone treatment are interpreted in terms of feasible local conformational changes affecting the secondary structure of the protein. Taken as a whole, the FTIR data suggests that the terminal D fragments of fibrinogen are markedly more susceptible to the ozone-induced oxidation than the central E fragment. The data on elastic and dynamic light scattering provide evidence that, in the presence of FXIIIa, both the unoxidized and the oxidized fibrinogen molecules bind to one another in an "end-to-end" fashion to form the flexible covalently cross-linked fibrinogen homopolymers. The γ and α polypeptide chains of the oxidized fibrinogen proved to be involved in the enzymatic cross-linking more readily than those of unaffected fibrinogen. The experimental data

  10. Plasma amino acid response to graded levels of escape protein.

    PubMed

    Gibb, D J; Klopfenstein, T J; Britton, R A; Lewis, A J

    1992-09-01

    A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

  11. Plasma BDNF levels following weight recovery in anorexia nervosa.

    PubMed

    Phillips, Kathryn E; Jimerson, David C; Pillai, Anilkumar; Wolfe, Barbara E

    2016-10-15

    Preclinical studies have implicated brain-derived neurotrophic factor (BDNF) in the regulation of eating behavior and body weight. As reviewed in this report, prior studies of BDNF levels in anorexia nervosa have yielded variable results, perhaps reflecting effects of malnutrition and psychiatric comorbidity. The goal of the current report was to assess plasma BDNF as a biomarker in weight-recovered individuals with a history of anorexia nervosa (ANWR). Study groups included women meeting criteria for ANWR and healthy female controls. Participants were in a normal weight range, free of current major psychiatric disorder, and free of medication. Self-ratings included eating disorder symptoms, depression and anxiety. Plasma BDNF levels were measured by enzyme linked immunoassay. Plasma BDNF levels were not significantly different for ANWR and control groups. Plasma BDNF levels were inversely correlated with anxiety ratings in controls (p<0.02) but not in the ANWR group. This report provides new evidence that circulating BDNF concentrations do not differ in healthy controls and ANWR free of psychiatric comorbidity. Additionally, the data provide new information on the relationship between plasma BDNF and anxiety in these two study groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Relationship between plasma and saliva quinine levels in humans.

    PubMed

    Babalola, C P; Bolaji, O O; Ogunbona, F A; Dixon, P A

    1996-02-01

    The relationship between saliva and plasma levels of quinine was studied in four healthy volunteers. After a single oral dose of quinine sulfate (600 mg) to the volunteers, quinine was determined in both saliva and plasma simultaneously over a 48-h period by an ion pair reverse-phase high performance liquid chromatography method. The tmax (4.3 +/- 0.5 h) and elimination half-life (11.8 +/- 2.9 h) of quinine derived from saliva levels were comparable with those obtained from plasma levels (tmax = 2.8 +/- 0.2 h, t1/2 = 12.9 +/- 2.3 h). A significant correlation existed between the plasma and saliva concentrations of the drug (r = 0.93, n = 20, p < 0.001). The mean saliva/plasma quinine concentration ratio was 0.24 +/- 0.02. The results suggest that quinine is passively secreted into saliva and that saliva level determination may be useful as a noninvasive method in the evaluation of pharmacokinetic parameters and therapeutic drug monitoring of quinine.

  13. Fibrinogen-related proteins in ixodid ticks

    PubMed Central

    2011-01-01

    Background Fibrinogen-related proteins with lectin activity are believed to be part of the tick innate immune system. Several fibrinogen-related proteins have been described and characterised mainly on the basis of their cDNA sequences while direct biochemical evidence is missing. One of them, the haemolymph lectin Dorin M from the tick Ornithodoros moubata was isolated and characterised in more depth. Results Several fibrinogen-related proteins were detected in the haemolymph of ixodid ticks Dermacentor marginatus, Rhipicephalus appendiculatus, R. pulchellus, and R. sanguineus. These proteins were recognised by sera directed against the tick lectin Dorin M and the haemagglutination activity of the ticks R. appendiculatus and D. marginatus. Cross-reactivity of the identified proteins with antibodies against the fibrinogen domain of the human ficolin was also shown. The carbohydrate-binding ability of tick haemolymph was confirmed by haemagglutination activity assays, and this activity was shown to be inhibited by neuraminic acid and sialylated glycoproteins as well as by N-acetylated hexosamines. The fibrinogen-related proteins were shown to be glycosylated and they were localised in salivary glands, midguts, and haemocytes of D. marginatus. Hemelipoglycoprotein was also recognised by sera directed against the fibrinogen-related proteins in all three Rhipicephalus species as well as in D. marginatus. However, this protein does not contain the fibrinogen domain and thus, the binding possibly results from the structure similarity between hemelipoglycoprotein and the fibrinogen domain. Conclusions The presence of fibrinogen-related proteins was shown in the haemolymph of four tick species in high abundance. Reactivity of antibodies directed against ficolin or fibrinogen-related proteins with proteins which do not contain the fibrinogen domain points out the importance of sequence analysis of the identified proteins in further studies. Previously observed expression of

  14. Plasma ionized magnesium levels in neonatal respiratory distress syndrome.

    PubMed

    Sarici, S Umit; Serdar, Muhittin A; Erdem, Gülşen; Alpay, Faruk; Tekinalp, Gülsevin; Yurdakök, Murat; Yigit, Sule; Gökcay, Erdal

    2004-01-01

    Measurement of ionized magnesium (IMg) provides an accurate assessment of the free form of Mg, which is the physiologically active form and is most reflective of the biologically active and not easily measurable intracellular Mg fraction. Plasma levels of IMg were measured by ion-selective electrode method in premature newborns with respiratory distress syndrome (RDS), and relationships and correlations between IMg levels and various demographic, prognostic and laboratory characteristics were investigated by comparing the premature newborns with (study group; n = 19) and without RDS (control group; n = 20) in the present study. The values of the postnatal arterial pH and base excess and plasma IMg levels were significantly different between the study and control groups, and the number of newborns with any morbidity was significantly higher in the study group. Within the study group there were significant negative correlations between the plasma IMg levels and the values of the umbilical cord arterial pH (r = -0.621, p = 0.005) and base excess (r = -0.746, p = 0.001), and the value of the postnatal arterial base excess (r = -0.585, p = 0.008). The newborns who died later had higher plasma IMg levels than those who survived (0.89 +/- 0.45 vs. 0.63 +/- 0.24 mmol/l, p = 0.026). These findings suggest that increase of plasma IMg may be due to extracellular movement of Mg, which is a principally intracellular ion, as a result of acidosis, hypoxia and probable cellular injury during the early course of RDS. The exact pathophysiological mechanism responsible for IMg increase, and whether determination of plasma IMg level, including umbilical cord blood IMg measurement, can be used as an early or predictive indicator of RDS in the diagnosis remain to be determined in further large-scale studies. Copyright 2004 S. Karger AG, Basel

  15. FDP-E induces adipocyte inflammation and suppresses insulin-stimulated glucose disposal: effect of inflammation and obesity on fibrinogen Bβ mRNA.

    PubMed

    Kang, Minsung; Vaughan, Roger A; Paton, Chad M

    2015-12-01

    Obesity is associated with increased fibrinogen production and fibrin formation, which produces fibrin degradation products (FDP-E and FDP-D). Fibrin and FDPs both contribute to inflammation, which would be expected to suppress glucose uptake and insulin signaling in adipose tissue, yet the effect of FDP-E and FDP-D on adipocyte function and glucose disposal is completely unknown. We tested the effects of FDPs on inflammation in 3T3-L1 adipocytes and primary macrophages and adipocyte glucose uptake in vitro. High-fat-fed mice increased hepatic fibrinogen mRNA expression ninefold over chow-fed mice, with concomitant increases in plasma fibrinogen protein levels. Obese mice also displayed increased fibrinogen content of epididymal fat pads. We treated cultured 3T3-L1 adipocytes and primary macrophages with FDP-E, FDP-D, or fibrinogen degradation products (FgnDP-E). FDP-D and FgnDP-E had no effect on inflammation or glucose uptake. Cytokine mRNA expression in RAW264.7 macrophage-like cells and 3T3-L1 adipocytes treated with FDP-E induced inflammation with maximal effects at 100 nM and 6 h. Insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake was reduced by 71% in adipocytes treated with FDP-E. FDP-E, but not FDP-D or FgnDP-E, induces inflammation in macrophages and adipocytes and decreases glucose uptake in vitro. FDP-E may contribute toward obesity-associated acute inflammation and glucose intolerance, although its chronic role in obesity remains to be elucidated. Copyright © 2015 the American Physiological Society.

  16. The effect of alcohol ingestion on the exercise-induced changes in fibrin and fibrinogen degradation products in man.

    PubMed

    El-Sayed, M S; Nieuwenhuizen, W

    2000-06-01

    The present study examined the influence of ingesting a moderate dose of alcohol on plasminogen activator activity (t-PA), plasma fibrinogen (Fb), total degradation products (TDP) and the degradation products of fibrin (FbDP) and fibrinogen (FgDP) at rest and in response to exercise. Eleven male subjects performed two separate experimental trials at an exercise intensity corresponding to 70% maximal oxygen consumption for 35 min. Prior to trials, subjects were either given 0.5 g/kg alcohol in orange-flavoured drink or an equal volume of non-caloric non-alcoholic drink 45 min before exercise. Comparison of the levels of t-PA, Fb, TDP, FbDP, and FgDP at rest, before and 45 min after the ingestion of alcohol revealed no significant differences between alcohol and control experiments. Exercise resulted in a marked increase in t-PA, TDP, and FgDP, with no appreciable change in FbDP. Although plasma fibrinogen level showed significant decrease post-exercise when subjects ingested alcohol, this difference was small and its biological significance is questionable. While t-PA level increased similarly in response to exercise during alcohol and control trials, a significantly higher response of TDP was found during the control trial compared with alcohol trial. It was concluded that exercise with and without alcohol ingestion is followed by a substantial increase in t-PA, which coincided with an increase in TDP. The increase in TDP was mainly due to an increase in FgDP, but not to FbDP. These findings support the hypothesis that a significant fibrinogenolysis occurs in response to exercise, and moderate intoxication with alcohol prior to exercise reduced this response.

  17. Relationship of blood cadmium level to hypertension and plasma norepinephrine level: a Romanian study (41159)

    SciTech Connect

    Revis, N.W.; Zinsmeister, A.R.

    1981-06-01

    The associations of blood cadmium levels with hypertension and plasma norepinephrine concentrations were determined in normotensive and hypertensive nonsmokers and smokers. Statistical analysis showed that after adjustment for age alone, the estimated mean values of blood cadmium and plasma norepinephrine in nonsmokers were significantly lower than in smokers. However, after adjustment for age and blood cadmium, the estimated mean values for plasma norepinephrine were not significantly different between nonsmokers and smokers or normotensives and hypertensives. In contrast the estimated mean value for blood cadmium as a function of blood pressure and smoking habit was still significant after adjustment for age and plasma norepinephrine. We suggest that smoking and blood pressure affect the level of blood cadmium, and through this change in blood cadmium the level of plasma norepinephrine is affected.

  18. Thrombolytic therapy reduces red blood cell aggregation in plasma without affecting intrinsic aggregability.

    PubMed

    Ben-Ami, R; Sheinman, G; Yedgar, S; Eldor, A; Roth, A; Berliner, A S; Barshtein, G

    2002-03-15

    Red blood cell (RBC) aggregation may contribute to occlusion of the coronary microcirculation during myocardial infarction. We studied the effect of thrombolytic therapy on RBC aggregation in patients with acute myocardial infarction (AMI). Compared with patients with myocardial infarction who did not receive thrombolytic therapy, those treated with systemic thrombolysis exhibited significantly reduced RBC aggregation, reduced plasma fibrinogen levels and increased plasma D-dimer levels. Using measurement of RBC aggregation in a standardized dextran-500 solution, reduction in RBC aggregation after thrombolysis was shown to be plasma dependent. Thrombolytic therapy had no direct effect on intrinsic RBC aggregability in patients with AMI. We conclude that thrombolytic therapy has rheologic consequences that may contribute to its overall efficacy. Inhibition of RBC aggregation by thrombolytic therapy may result from the degradation of fibrinogen, a key factor in the formation of RBC aggregates, and from the generation of fibrinogen degradation products capable of disaggregating RBCs.

  19. Assessing Stress in Arctic Lemmings: Fecal Metabolite Levels Reflect Plasma Free Corticosterone Levels.

    PubMed

    Fauteux, Dominique; Gauthier, Gilles; Berteaux, Dominique; Bosson, Curtis; Palme, Rupert; Boonstra, Rudy

    Interest in the ecology of stress in wild populations has triggered the development of noninvasive methods for quantifying stress hormones. Measurement of fecal corticosteroid metabolites (FCMs) is one such method, but it is still unclear whether FCMs can be a reliable proxy of free plasma glucocorticoids. To assess the validity of this assumption, we carried out a robust assessment on brown lemmings (Lemmus trimucronatus) from Bylot Island, Nunavut, Canada, that were hand captured and anesthetized and related plasma glucocorticoid levels to fecal metabolite glucocorticoid levels. We examined endogenous factors that could explain interindividual variability. Blood corticosterone was measured from samples obtained on capture and 30 min later, and FCM levels were measured from animals kept in captivity for 72 h. Plasma free corticosterone increased 135-fold over baseline values 30 min after capture, which confirmed that initial handling was perceived as a stressor. We found that FCM levels were highly related with free (marginal [Formula: see text] = 0.53) but not with total ([Formula: see text] = 0.02) corticosterone levels, regardless of age, sex, and reproductive condition. FCM levels started increasing 2 h after capture and reached maximum levels 4 h after capture. No circadian rhythm in FCMs was found. Plasma total corticosterone levels were much higher in adult females compared with adult males, but this difference was much smaller when measuring free corticosterone levels and FCM levels. Our results suggest that FCM levels are good measures of stress by being closely related to plasma free corticosterone levels in brown lemmings.

  20. Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition.

    PubMed

    Languino, L R; Duperray, A; Joganic, K J; Fornaro, M; Thornton, G B; Altieri, D C

    1995-02-28

    Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.

  1. Integrin-associated protein (CD47) is a putative mediator for soluble fibrinogen interaction with human red blood cells membrane.

    PubMed

    De Oliveira, S; Vitorino de Almeida, V; Calado, A; Rosário, H S; Saldanha, C

    2012-03-01

    Fibrinogen is a multifunctional plasma protein that plays a crucial role in several biological processes. Elevated fibrinogen induces erythrocyte hyperaggregation, suggesting an interaction between this protein and red blood cells (RBCs). Several studies support the concept that fibrinogen interacts with RBC membrane and this binding, due to specific and non-specific mechanisms, may be a trigger to RBC hyperaggregation in inflammation. The main goals of our work were to prove that human RBCs are able to specifically bind soluble fibrinogen, and identify membrane molecular targets that could be involved in this process. RBCs were first isolated from blood of healthy individuals and then separated in different age fractions by discontinuous Percoll gradients. After isolation RBC samples were incubated with human soluble fibrinogen and/or with a blocking antibody against CD47 followed by fluorescence confocal microscopy, flow cytometry acquisitions and zeta potential measurements. Our data show that soluble fibrinogen interacts with the human RBC membrane in an age-dependent manner, with younger RBCs interacting more with soluble fibrinogen than the older cells. Importantly, this interaction is abrogated in the presence of a specific antibody against CD47. Our results support a specific and age-dependent interaction of soluble fibrinogen with human RBC membrane; additionally we present CD47 as a putative mediator in this process. This interaction may contribute to RBC hyperaggregation in inflammation. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Plasma separation: physical separation at the molecular level

    NASA Astrophysics Data System (ADS)

    Gueroult, Renaud; Rax, Jean-Marcel; Fisch, Nathaniel J.

    2016-09-01

    Separation techniques are usually divided in two categories depending on the nature of the discriminating property: chemical or physical. Further to this difference, physical and chemical techniques differ in that chemical separation typically occurs at the molecular level, while physical separation techniques commonly operate at the macroscopic scale. Separation based on physical properties can in principle be realized at the molecular or even atomic scale by ionizing the mixture. This is in essence plasma based separation. Due to this fundamental difference, plasma based separation stands out from other separation techniques, and features unique properties. In particular, plasma separation allows separating different elements or chemical compounds based on physical properties. This could prove extremely valuable to separate macroscopically homogeneous mixtures made of substances of similar chemical formulation. Yet, the realization of plasma separation techniques' full potential requires identifying and controlling basic mechanisms in complex plasmas which exhibit suitable separation properties. In this paper, we uncover the potential of plasma separation for various applications, and identify the key physics mechanisms upon which hinges the development of these techniques.

  3. Plasma bilirubin level and oxidative stress in preterm infants

    PubMed Central

    Dani, C; Martelli, E; Bertini, G; Pezzati, M; Filippi, L; Rossetti, M; Rizzuti, G; Rubaltelli, F

    2003-01-01

    Objective: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. Methods: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. Results: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. Conclusion: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin. PMID:12598500

  4. Plasma bilirubin level and oxidative stress in preterm infants.

    PubMed

    Dani, C; Martelli, E; Bertini, G; Pezzati, M; Filippi, L; Rossetti, M; Rizzuti, G; Rubaltelli, F F

    2003-03-01

    To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.

  5. Congenital hypofibrinogenemia associated with novel homozygous fibrinogen Aα and heterozygous Bβ chain mutations.

    PubMed

    Castaman, Giancarlo; Rimoldi, Valeria; Giacomelli, Sofia H; Duga, Stefano

    2015-07-01

    We report the molecular characterisation of two novel cases of inherited hypofibrinogenemia. After sequencing all coding regions and intron-exon boundaries of the three fibrinogen genes (FGA, FGB, and FGG), two different novel mutations were found, one homozygous and one heterozygous. The first patient, with a mild bleeding history and mild discrepancy between functional and immunological fibrinogen, showed a novel homozygous nonsense mutation in exon 5 of FGA (p.Trp373*, p.Trp354* according to the mature protein) caused by a G>A transition at nucleotide position 1,119. The resulting truncation in the Aα chain is likely to reduce the efficiency of fibrinogen assembly and secretion. The second patient, referred after ischemic stroke (functional fibrinogen 77mg/dL), had a novel heterozygous splicing mutation in intron 5 of FGB (IVS5+2T>A or c.832+2T>A), which we demonstrated to cause either exon 5 skipping or the inclusion of 75bp belonging to intron 5. Neither splicing defect alters the reading frame: one results in a 38-residue deletion and the other in a 25-residue insertion in the D domain of fibrinogen Bβ chain. This report confirms that genetically determined partial deficiencies of fibrinogen with levels greater than 50mg/dL are rarely associated with significant bleeding symptoms and that homozygous null mutations removing a significant portion of the Aα chain may be associated with mild fibrinogen deficiency.

  6. A method to measure thrombin activity in a mixture of fibrinogen and thrombin powders

    PubMed Central

    DeAnglis, Ashley P.; Nur, Israel; Gorman, Anne J.; Meidler, Roberto

    2017-01-01

    Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders. PMID:26991860

  7. A method to measure thrombin activity in a mixture of fibrinogen and thrombin powders.

    PubMed

    DeAnglis, Ashley P; Nur, Israel; Gorman, Anne J; Meidler, Roberto

    2017-03-01

    Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders.

  8. Utilisation of Quartz Crystal Microbalance Sensors with Dissipation (QCM-D) for a Clauss Fibrinogen Assay in Comparison with Common Coagulation Reference Methods.

    PubMed

    Oberfrank, Stephanie; Drechsel, Hartmut; Sinn, Stefan; Northoff, Hinnak; Gehring, Frank K

    2016-02-24

    The determination of fibrinogen levels is one of the most important coagulation measurements in medicine. It plays a crucial part in diagnostic and therapeutic decisions, often associated with time-critical conditions. The commonly used measurement is the Clauss fibrinogen assay (CFA) where plasma is activated by thrombin reagent and which is conducted by mechanical/turbidimetric devices. As quartz crystal microbalance sensors with dissipation (QCM-D) based devices have a small footprint, can be operated easily and allow measurements independently from sample transportation time, laboratory location, availability and opening hours, they offer a great opportunity to complement laboratory CFA measurements. Therefore, the objective of the work was to (1) transfer the CFA to the QCM-D method; (2) develop an easy, time- and cost-effective procedure and (3) compare the results with references. Different sensor coatings (donor's own plasma; gold surface) and different QCM-D parameters (frequency signal shift; its calculated turning point; dissipation signal shift) were sampled. The results demonstrate the suitability for a QCM-D-based CFA in physiological fibrinogen ranges. Results were obtained in less than 1 min and in very good agreement with a standardized reference (Merlin coagulometer). The results provide a good basis for further investigation and pave the way to a possible application of QCM-D in clinical and non-clinical routine in the medical field.

  9. Utilisation of Quartz Crystal Microbalance Sensors with Dissipation (QCM-D) for a Clauss Fibrinogen Assay in Comparison with Common Coagulation Reference Methods

    PubMed Central

    Oberfrank, Stephanie; Drechsel, Hartmut; Sinn, Stefan; Northoff, Hinnak; Gehring, Frank K.

    2016-01-01

    The determination of fibrinogen levels is one of the most important coagulation measurements in medicine. It plays a crucial part in diagnostic and therapeutic decisions, often associated with time-critical conditions. The commonly used measurement is the Clauss fibrinogen assay (CFA) where plasma is activated by thrombin reagent and which is conducted by mechanical/turbidimetric devices. As quartz crystal microbalance sensors with dissipation (QCM-D) based devices have a small footprint, can be operated easily and allow measurements independently from sample transportation time, laboratory location, availability and opening hours, they offer a great opportunity to complement laboratory CFA measurements. Therefore, the objective of the work was to (1) transfer the CFA to the QCM-D method; (2) develop an easy, time- and cost-effective procedure and (3) compare the results with references. Different sensor coatings (donor’s own plasma; gold surface) and different QCM-D parameters (frequency signal shift; its calculated turning point; dissipation signal shift) were sampled. The results demonstrate the suitability for a QCM-D-based CFA in physiological fibrinogen ranges. Results were obtained in less than 1 min and in very good agreement with a standardized reference (Merlin coagulometer). The results provide a good basis for further investigation and pave the way to a possible application of QCM-D in clinical and non-clinical routine in the medical field. PMID:26927107

  10. Plasma lipid levels in preterm neonates receiving parenteral fat emulsions.

    PubMed Central

    Hilliard, J L; Shannon, D L; Hunter, M A; Brans, Y W

    1983-01-01

    Concentrations of various plasma lipid fractions were determined during 96 hours of continuous parenteral infusions of lipid emulsions in 10 normally-grown neonates whose birth-weights ranged from 960 to 1760 g and whose gestational ages ranged from 26 to 32 weeks. Total lipid, triglyceride, free glycerol, and free fatty acid concentrations were measured. During lipid infusions, mean plasma concentrations of all lipid fractions increased above the mean preinfusion values if 2 g/kg a day or more of lipid emulsion was used. There were no further significant increases in mean plasma lipid levels if the infused dosage was increased to 3 or 4 g/kg a day. At these higher infusion rates however, there were considerable individual variations. The only neonate less than 27 weeks of gestation had plasma lipid levels severalfold higher than any of his peers, his plasma was frankly creamy on visual inspection, and the study had to be stopped. Further investigations are needed to determine the optimal modalities of parenteral nutrition with fat emulsions. PMID:6402989

  11. Modulation of Human Plasma Fibronectin Levels Following Exercise,

    DTIC Science & Technology

    1988-01-01

    increased under conditions of pathology, such as in obesity (6). cancer (3). proteinuria (4). diabetic retinopathy (5). and preeclampsia (27). in the absence...Res. 1977: 22:709-716. 27. Stubbs. T.M.. Lazarchick. J.. and Horger. E.O. Plasma fibronectin levels in preeclampsia : A possible biochemical marker

  12. Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon.

    PubMed

    Kabadi, U M; Eisenstein, A B; Konda, J

    1985-03-01

    Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack of conversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretagogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon, and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p less than 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls; whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p less than 0.05), as well as with glucagon response (r = 0.65, p less than 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics, with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.

  13. Progesterone and estradiol plasma levels in neonatally irradiated cycling rats

    SciTech Connect

    Freud, A.; Sod-Moriah, U.A. )

    1990-01-01

    Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. The possibility that the impaired fertility resulted from altered ovarian activity as reflected by changes in plasma levels of progesterone or estardiol was investigated. Plasma levels of both steroids were determined throughout the day of proestrus. Progesterone level was also determined in 6R animals on the day of weaning. The maturity of such irradiated rats was assessed by observing the time of vaginal opening. The results indicated that the preovulatory peak of progesterone was delayed in the 6R rats whereas in the 15R group its levels were significantly lower. On the other hand no differences in estradiol plasma levels were noticed between the groups. The higher level of progesterone in the 6R animals was not evident on the day of weaning and was even in both groups, but vaginal opening in the irradiated rats was significantly delayed. The elevated level of progesterone might be responsible, among other endocrine changes, for the lower fertility of neonatally irradiated mature female rats.

  14. Plasma ghrelin levels in patients with Familial Mediterranean Fever.

    PubMed

    Keskin, Göksal; Inal, Ali; Ilikçi, Rahşan; Baysal, Ozan

    2009-01-01

    Familial mediterranean fever (FMF) is a familial disease characterized by recurrent episodes of febrile serositis, peritonitis, arthritis and pleuritis. Many studies have been performed is an attempt to understand the basis of the inflammatory attacts in FMF. Ghrelin, a recently described orexigene peptide is predominantly produced by stomach. Ghrelin also exerts multiple regulatory effects on immune system. It has reported that grelin has anti-inflammatory effects. There is currently no published evidence demonstrating a role for anti-inflammatory effects of ghrelin in FMF. For this reason, we investigated the role of plasma ghrelin levels in patients with FMF. Thirty seven patients with FMF and 10 healthy controls (5 female, 5 male; mean age 35.4 +/- 5.6 years) were enrolled in this study. Twenty-one patients were in active stage (10 female, 11 male, mean age; 31.0 +/- 5.4 years, mean disease duration 7.2 +/- 3.3 years) and 16 patients were in inactive stage (7 female,9 male, mean age; 33.0 +/- 6.0 years, mean disease duration; 8.7 +/- 3.2 years). Plasma ghrelin levels were determined by EIA. The mean plasma ghrelin levels were 158.4 +/- 52.9 pg/ml in patients with FMF and 56.7 +/- 7.5 pg/ml in healthy controls. The mean plasma ghrelin levels were 190.5 +/- 49.4 pg/ml in the active patients and 116.2 +/- 11.7 pg/ml in the inactive patients. Plasma ghrelin levels were significantly high in patients with FMF compared to healthy controls (p<0.001). Plasma ghrelin levels were significantly high in the active patients compared to in the inactive patients and healthy controls (p<0.001 and p<0.001 respectively). There was significantly difference between in active and inactive patients with FMF (p<0.001). As a results; Plasma ghrelin levels were high both in active and inactive patients with FMF. It is showed that ghrelin may play significant role of the pathogenesis of FMF.

  15. Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise.

    PubMed

    Tékus, Éva; Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta

    2017-02-01

    The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p < 0.05), as well as baseline and the highest value of post-exercise AGP (p < 0.05). Relationships were found between GSN levels and other indirect EIMD markers (between all GSN levels at post-exercise and CK activity at 6 h, p < 0.05; GSNMIN and muscle soreness at post-exercise, p < 0.04), GSN and AGP; however, actin did not correlate at any time points with GSN. Actin, GSN, AGP and CK responses after eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury.

  16. Level shifts and inelastic electron scattering in dense plasmas

    NASA Technical Reports Server (NTRS)

    Davis, J.; Blaha, M.

    1982-01-01

    A completely quantum mechanical formalism has been developed to describe the high density plasma effects on fundamental atomic parameters. Both the bound and free electrons are treated by a method which in principle is similar to Hartree's self-consistent field method. The free plasma electrons' wavefunction is obtained from the Schroedinger equation with the effective potential representing the spherically averaged Coulomb interaction with bound and free electrons. Results are given for level shifts, coefficients of transition probabilities, and electron collision cross sections of Ne(9+) for temperatures of 200 and 500 eV for an electron density range of 1-6 x 10 to the 24th per cu cm.

  17. Human traumatic brain injury alters plasma microRNA levels.

    PubMed

    Redell, John B; Moore, Anthony N; Ward, Norman H; Hergenroeder, Georgene W; Dash, Pramod K

    2010-12-01

    Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.

  18. Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins

    SciTech Connect

    Jin, Hongjun; Webb-Robertson, Bobbie-Jo M.; Peterson, Elena S.; Tan, Ruimin; Bigelow, Diana J.; Scholand, Mary Beth; Hoidal, John R.; Pounds, Joel G.; Zangar, Richard C.

    2011-09-01

    BACKGROUND: Nitric oxide is a physiologically regulator of endothelial function and hemodynamics. Oxidized products of nitric oxide can form nitrotyrosine, which is a marker of nitrative stress. Cigarette smoking decreases exhaled nitric oxide, and the underlying mechanism may be important in the cardiovascular toxicity of cigarette smoke, although it is not clear if this effect results from decreased nitric oxide production or oxidation of nitric oxide to reactive, nitrating, species. These processes would be expected to have opposite effects on nitrotyrosine levels, a marker of nitrative stress. OBJECTIVE: In this study, we determine the effects of smoking and chronic obstructive pulmonary disease (COPD) on circulating levels of nitrotyrosine, and thereby gain insight into the processes regulating nitrotyrosine formation. METHODS: A custom antibody microarray platform was used to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. Plasma samples from 458 individuals were analyzed. RESULTS: Nitrotyrosine levels in circulating proteins were uniformly reduced in smokers but increased in COPD patients. We also observed a persistent suppression of nitrotyrosine in former smokers. CONCLUSIONS: Smoking broadly suppresses the levels of 3-nitrotyrosine in plasma proteins, suggesting that cigarette smoke suppresses endothelial nitric oxide production. In contrast, the increase in nitrotyrosine levels in COPD patients most likely results from inflammatory processes. This study provides the first evidence that smoking has irreversible effects on endothelial production of nitric oxide, and provides insight into how smoking could induce a loss of elasticity in the vasculature and a long-term increase in the risk of cardiovascular disease.

  19. Plasma immunoreactive relaxin levels in pregnant and nonpregnant women.

    PubMed

    O'Byrne, E M; Carriere, B T; Sorensen, L; Segaloff, A; Schwabe, C; Steinetz, B G

    1978-11-01

    Immunoreactive relaxin was measured in plasma samples obtained from human volunteers utilizing the RIA procedure of Sherwood et al., as modified by O'Byrne and Steinetz for heterologous plasma samples. Immunoreactive hormone was not detected in samples obtained from men, and only rarely in plasma of nonpregnant women. Immunoreactive relaxin was present as early as the fourth week of pregnancy and was detectable throughout the course of gestation. Immunoreactive relaxin tended to be higher early in pregnancy, and there was no peak just before parturition as occurs in many other species. Our results are at variance with those of Bryant and coworkers, who reported high levels of immunoreactive relaxin in men and nonpregnant as well as pregnant women. The possible reasons for this discrepancy are presented.

  20. Changes in plasma taurine levels after different endurance events.

    PubMed

    Ward, R J; Francaux, M; Cuisinier, C; Sturbois, X; De Witte, P

    1999-01-01

    The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.

  1. Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1987-01-01

    The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.

  2. Plasma levels of S100A4 in portopulmonary hypertension.

    PubMed

    Peng, Tien; Zamanian, Roham; Krowka, Michael J; Benza, Raymond L; Roberts, Kari E; Taichman, Darren B; Rybak, Debbie; Trotter, James F; Brown, Robert S; Fallon, Michael B; Kawut, Steven M

    2009-05-01

    We previously showed that a single nucleotide polymorphism in S100A4 was associated with portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure >25 mmHg, pulmonary vascular resistance >240 dynes s cm(-5) and pulmonary capillary wedge pressure Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 controls with liver disease. There was no difference in mean age between cases and controls (p = 0.52). Seventy-nine percent of cases were female compared with 44% of controls (p = 0.03). There was no difference in S100A4 levels between cases and controls (p = 0.58). Both groups had significantly higher S100A4 levels than healthy volunteers (p <0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.

  3. Plasma Levels of S100A4 in Portopulmonary Hypertension

    PubMed Central

    Peng, Tien; Zamanian, Roham; Krowka, Michael J.; Benza, Raymond L.; Roberts, Kari E.; Taichman, Darren B.; Rybak, Debbie; Trotter, James F.; Brown, Robert S.; Fallon, Michael B.; Kawut, Steven M.

    2010-01-01

    We previously showed that a single nucleotide polymorphism in S100A4 was associated with developing portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes-sec · cm−5, and pulmonary capillary wedge pressure ≤15 mm Hg. Controls with liver disease had right ventricular systolic pressure < 40 mm Hg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 liver disease controls. The mean age for both cases and controls was 52 ± 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.02). There was no difference in S100A4 levels between cases and controls (p = 0.53). Both groups had significantly higher S100A4 levels than healthy volunteers (p < 0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels. PMID:19399660

  4. The platelet fibrinogen receptor: an immunogold-surface replica study of agonist-induced ligand binding and receptor clustering

    PubMed Central

    1987-01-01

    Platelet aggregation requires the binding of fibrinogen to its receptor, a heterodimer consisting of the plasma-membrane glycoproteins (GP) IIb and IIIa. Although the GPIIb-IIIa complex is present on the surface of unstimulated platelets, it binds fibrinogen only after platelet activation. We have used an immunogold-surface replica technique to study the distribution of GPIIb-IIIa and bound fibrinogen over broad areas of surface membranes in unstimulated, as well as thrombin-activated and ADP-activated human platelets. We found that the immunogold-labeled GPIIb-IIIa was monodispersed over the surface of unstimulated platelets, although the cell surface lacked immunoreactive fibrinogen. On thrombin-stimulated platelets, approximately 65% of the GPIIb-IIIa molecules were in clusters within the plane of the membrane. Fibrinogen, which had been released from the alpha-granules of these cells, bound to GPIIb-IIIa on the cell surface and was similarly clustered. To determine whether the receptors clustered before ligand binding, or as a consequence thereof, we studied the surface distribution of GPIIb-IIIa after stimulation with ADP, which causes activation of the fibrinogen receptor function of GPIIb-IIIa without inducing the release of fibrinogen. In the absence of added fibrinogen, the unoccupied, yet binding-competent receptors on ADP-stimulated platelets were monodispersed. The addition of fibrinogen caused the GPIIb-IIIa molecules to cluster on the cell surface. Clustering was also induced by the addition of the GPIIb-IIIa-binding domains of fibrinogen, namely the tetrapeptide Arg-Gly-Asp-Ser on the alpha-chain or the gamma-chain decapeptide gamma 402-411. These results show that receptor occupancy causes clustering of GPIIb-IIIa in activated platelets. PMID:3584243

  5. Surface plasmon resonance analysis of immobilized fibrinogen and fibrin and their interaction with thrombin and fibrinogen

    NASA Astrophysics Data System (ADS)

    Dyr, Jan E.; Jirouskova, Marketa; Rysava, Jitka; Tichy, Ivo; Tobiska, Petr; Slavik, Radan; Homola, Jiri; Suttnar, Jiri

    1999-01-01

    The exploitation of surface plasmon resonance optical sensor for the study of the interaction of immobilized fibrinogen and fibrin monomer with soluble fibrinogen and thrombin is reported. Soluble fibrinogen was mostly reversible, the bound thrombin could be inhibited by milimolar concentration of phenylmethylsulphonyl fluoride (PMSF). At lease three sets of different thrombin binding sites were found. There was a residual fraction of thrombin bound to washed fibrin (ogin) (to about a five to ten percent of fibron monomer units) suggesting that a known naturally occurring fibrinogen variant differing in the gamma chain was the target. Surface bound fibrinogen was converted by thrombin to fibrin monomer that interacted with fibrinogen in solution. At low fibrin monomer surface density the second layer was formed that contained about the same amount of protein as the first layer, at higher fibrin monomer concentration less than one molecule of fibrinogen per molecule of fibrin monomer was captured. Starting with surface-bound fibrinogen and alternating addition of thrombin and fibrinogen a fibrin network of predetermined composition, size, and arrangement could be formed.

  6. Low and intermediate level radioactive waste processing in plasma reactor

    SciTech Connect

    Sauchyn, V.; Khvedchyn, I.; Van Oost, G.

    2013-07-01

    Methods of low and intermediate level radioactive waste processing comprise: cementation, bituminization, curing in polymer matrices, combustion and pyrolysis. All these methods are limited in their application in the field of chemical, morphological, and aggregate composition of material to be processed. The thermal plasma method is one of the universal methods of RAW processing. The use of electric-arc plasma with mean temperatures 2000 - 8000 K can effectively carry out the destruction of organic compounds into atoms and ions with very high speeds and high degree of conversion. Destruction of complex substances without oxygen leads to a decrease of the volume of exhaust gases and dimension of gas cleaning system. This paper presents the plasma reactor for thermal processing of low and intermediate level radioactive waste of mixed morphology. The equipment realizes plasma-pyrolytic conversion of wastes and results in a conditioned product in a single stage. As a result, the volume of conditioned waste is significantly reduced (more than 10 times). Waste is converted into an environmentally friendly form that suits long-term storage. The leaching rate of macro-components from the vitrified compound is less than 1.10{sup -7} g/(cm{sup 2}.day). (authors)

  7. [Interaction of fibrinogen with magnetite nanoparticles].

    PubMed

    Bychkova, A V; Sorokina, O N; Kovarskiĭ, A L; Shapiro, A B; Leonova, V B; Rozenfel'd, M A

    2010-01-01

    The interaction between fibrinogen and magnetite nanoparticles in solution has been studied by the methods of spin labeling, ferromagnetic resonance, dynamic and Rayleigh light scattering. It was shown that protein molecules adsorb on the surface of nanoparticles to form multilayer protein covers. The number of molecules adsorbed on one nanoparticle amounts to approximately 65 and the thickness of the adsorption layer amounts to approximately 27 nm. Separate nanoparticles with fibrinogen covers (clusters) form aggregates due to interactions of the end D-domains of fibrinogen. Under the influence of direct magnetic field, nanoparticles with adsorbed proteins form linear aggregates parallel to force lines. It was shown that the rate of protein coagulation during the formation of fibrin gel under the action of thrombin on fibrinogen decreases approximately 2 times in the presence of magnetite nanoparticles, and the magnitude of the average fiber mass-length ratio grows.

  8. Interactions of Bacteroides gingivalis with fibrinogen.

    PubMed Central

    Lantz, M S; Rowland, R W; Switalski, L M; Höök, M

    1986-01-01

    Results of previous studies from our laboratory have shown that a strain of Bacteroides intermedius isolated originally from a patient with acute necrotizing ulcerative gingivitis binds and degrades human fibrinogen (M.S. Lantz, L.M. Switalski, K.S. Kornman, and M. Hook, J. Bacteriol. 163:623-628, 1985). We report that strains of Bacteroides gingivalis, an organism implicated in the etiology of several forms of periodontitis, also bind and degrade fibrinogen. The binding is rapid, reversible, saturable, and specific. The number of fibrinogen-binding sites per cell varies from 500 to 1,500 in different batches of bacteria, and the dissociation constant for the complex is on the order of 10(-8) M. B. gingivalis possesses cell-associated fibrinogenolytic activity that is activated by dithiothreitol and blocked by thiol protease inhibitors. Interaction with fibrinogen may mediate colonization and establishment of these organisms in the periodontal microbiota. Images PMID:3096886

  9. Plasma Leptin Levels in Children Hospitalized with Cholera in Bangladesh.

    PubMed

    Falkard, Brie; Uddin, Taher; Rahman, M Arifur; Franke, Molly F; Aktar, Amena; Uddin, Muhammad Ikhtear; Bhuiyan, Taufiqur Rahman; Leung, Daniel T; Charles, Richelle C; Larocque, Regina C; Harris, Jason B; Calderwood, Stephen B; Qadri, Firdausi; Ryan, Edward T

    2015-08-01

    Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in 11 children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V. cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V. cholerae lipopolysaccharide, a T cell-independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell-dependent antigens.

  10. Elevated plasma tricyclic levels with therapeutic doses of imipramine.

    PubMed

    Garvey, M J; Tuason, V B; Johnson, R A; Valentine, R H; Cooper, T B

    1984-07-01

    Nine (15%) of 59 patients treated with imipramine at doses of 150 to 300 mg/day had steady-state plasma levels greater than 500 ng/ml. Low capacity for hydroxylation was found in all six patients for whom hydroxy metabolites were measured. Maximum tricyclic levels in the nine study patients were comparable to levels found in tricyclic antidepressant overdoses (651-2439 ng/ml). No study patient experienced any adverse effects: QRS durations were all less than 100 msec, and a mildly dry mouth was the most commonly reported side effect (five of nine patients). Depressive symptoms recurred in three patients when their imipramine dose was decreased.

  11. Injected phytosterols/stanols suppress plasma cholesterol levels in hamsters.

    PubMed

    Vanstone, C A.; Raeini-Sarjaz, M; Jones, P J.H.

    2001-10-01

    Although plant sterols are known to suppress intestinal cholesterol absorption, whether plasma and hepatic lipid levels are influenced through non-gut related internal mechanisms has not been established. To examine this question 50 male hamsters were divided into 5 groups and fed semi-purified diets containing 20% energy as fat and 0.25% (w/w) cholesterol ad libitum for 60 days. The control group (i) received diet alone, while four additional groups consumed the diet plus one of four equivalent phytosterol mixtures (5 mg/kg/day) given either as (ii) tall oil phytosterols/stanols mixed with diet (oralSA), (iii) tall oil phytosterols/stanols subcutaneously injected (subSA), (iv) soybean oil phytosterols alone mixed with diet (oralSE), or (v) soybean oil subcutaneous injected phytosterols alone (subSE). The control group and both orally supplemented groups also received placebo subcutaneous sham injections. Neither food consumption, body weight, nor liver weight differed across treatment groups. Subcutaneous administration of SA and SE decreased plasma total cholesterol levels by 21% and 23% (p < 0.0001) and non-apolipoprotein-A cholesterol concentrations by 22% and 15% (p < 0.0002), respectively, compared to control. HDL cholesterol and TG concentrations remained unchanged across all groups, except for a decline of 25% (p < 0.0001) in HDL concentration in the subSE group versus control. Plasma campesterol levels were lower (p < 0.05) in the subSA group relative to all other groups. Plasma campesterol:cholesterol and campesterol:sitosterol ratios were, however, higher (p < 0.0001) for both the oral and subSE groups. Hepatic cholesterol levels were higher (p < 0.0001) in the oral and subSE phytosterol groups by 30% and 31%, respectively, relative to control. We conclude that low doses of subcutaneously administered plant sterols reduce circulating cholesterol levels through mechanisms other than inhibiting intestinal cholesterol absorption.

  12. Periodontal treatment decreases plasma oxidized LDL level and oxidative stress.

    PubMed

    Tamaki, Naofumi; Tomofuji, Takaaki; Ekuni, Daisuke; Yamanaka, Reiko; Morita, Manabu

    2011-12-01

    Periodontitis induces excessive production of reactive oxygen species in periodontal lesions. This may impair circulating pro-oxidant/anti-oxidant balance and induce the oxidation of low-density lipoprotein (LDL) in blood. The purpose of this study was to monitor circulating oxidized LDL and oxidative stress in subjects with chronic periodontitis following non-surgical periodontal treatment. Plasma levels of oxidized LDL and oxidative stress in 22 otherwise healthy non-smokers with chronic periodontitis (mean age 44.0 years) were measured at baseline and at 1 and 2 months after non-surgical periodontal treatment. At baseline, chronic periodontitis patients had higher plasma levels of oxidized LDL and oxidative stress than healthy subjects (p < 0.001). Periodontal treatment was associated with a significant reduction in plasma levels of oxidized LDL (oxLDL)(p < 0.001) and oxidative stress (p < 0.001). At 2 months after periodontal treatment, the degree of change in the oxLDL was positively correlated with that in the oxidative stress (r = 0.593, p = 0.004). These observations indicate that periodontitis patients showed higher levels of circulating oxLDL and oxidative stress than healthy subjects. In addition, improved oral hygiene and non-surgical periodontal treatment were effective in decreasing oxLDL, which was positively associated with a reduction in circulating oxidative stress.

  13. High plasma adenosine levels in overweight/obese pregnant women.

    PubMed

    Badillo, Priscila; Salgado, Paola; Bravo, Patricia; Guevara, Katherine; Acurio, Jesenia; Gonzalez, Maria Angelica; Oyarzun, Carlos; San Martin, Rody; Escudero, Carlos

    2017-07-18

    We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/μg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/μg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/μg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/μg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/μg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/μg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/μg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = -0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.

  14. Determination of plasma kinin and kininogen levels in man

    PubMed Central

    Brocklehurst, W. E.; Zeitlin, I. J.

    1967-01-01

    1. A method for the estimation of free plasma kinin and kininogen is described, which is suitable for samples of blood taken in hospital. 2. The method permits the assay of very low levels of kinin and substantially eliminates errors due to the presence of amines and other interfering substances. 3. In normal subjects the mean value of free kinin is 2·8 ng (bradykinin equivalent)/ml. plasma, and 6·1 μg kininogen/ml. 4. In vasovagal fainting, carcinoid flush, and dumping syndrome, during the phase of peripheral vasodilatation, the free kinin exceeds 10 ng/ml., and is often in excess of 30 ng/ml. 5. Sudden release of free kinin is accompanied by a fall in kininogen level. PMID:6050112

  15. The regulation of plasma relaxin levels during human pregnancy.

    PubMed

    Johnson, M R; Abbas, A A; Allman, A C; Nicolaides, K H; Lightman, S L

    1994-08-01

    The factors that determine the circulating levels of relaxin during pregnancy have been investigated by comparing the plasma levels of relaxin throughout pregnancy in women who became pregnant spontaneously (singleton, n = 240) or following superovulation (singleton and multifetal pregnancies (two to ten conceptuses), n = 83). Some of the women with multifetal pregnancies underwent selective fetal reduction to twin pregnancies. Relaxin levels were higher at 7-34 weeks of gestation in singleton pregnancies achieved following superovulation when compared with levels in spontaneously conceived singleton pregnancies (p < 0.05-0.001). In samples obtained between 10 and 12 weeks of gestation (before fetal reduction for the multifetal pregnancies), plasma relaxin levels correlated with fetal number (r = 0.526, P = 0.0001). Reduction in fetal number to a twin pregnancy did not alter relaxin levels. These data suggest that the circulating levels of relaxin throughout pregnancy are determined during the cycle of conception by gonadotrophin stimulation, and within the first 10 weeks of pregnancy by the luteotrophic stimulus from the conceptus. Furthermore, once corpus luteum synthesis of relaxin is established, then reduction in the luteotrophic stimulus does not appear to affect it.

  16. High fibrin/fibrinogen degradation product to fibrinogen ratio is associated with 28-day mortality and massive transfusion in severe trauma.

    PubMed

    Lee, D H; Lee, B K; Noh, S M; Cho, Y S

    2017-09-18

    There is a lack of association between coagulation biomarkers and long-term mortality in severe trauma. We aimed to investigate the association between coagulation biomarkers on admission and outcome of late stage of trauma. This retrospective observational study included patients admitted with severe trauma between 2012 and 2015. We used the area under the receiver operating characteristic curve (AUROC) of coagulation biomarkers to determine 28-day mortality. Head Abbreviated Injury Scale scores greater than 3 were defined as traumatic brain injury (TBI). The primary outcome was 28-day mortality and the secondary outcome was massive transfusion. Of the 1266 patients included in the study, 28-day mortality rate was 19.7% (n = 249) and 7.9% (n = 100) of patients received massive transfusion. The AUROC of fibrin/fibrinogen degradation product (FDP) to fibrinogen ratio had a significantly higher prognostic performance than other markers. Multivariate analysis revealed that D-dimer level [odds ratio (OR) 1.033; 95% confidence interval (CI) 1.016-1.051] and FDP/fibrinogen ratio (OR 1.007; 95% CI 1.001-1.013) were independently associated with 28-day mortality. D-dimer (OR 1.028; 95% CI 1.003-1.055) and FDP/fibrinogen ratio (OR 1.035; 95% CI 1.012-1.058) were associated with 28-day mortality in the TBI group. In the non-TBI group, D-dimer was associated with 28-day mortality (OR 1.033; 95% CI 1.008-1.059), but the FDP/fibrinogen ratio was not. FDP/fibrinogen ratio, not D-dimer level, was an independent predictor for massive transfusion (OR 1.005; 95% CI 1.001-1.010). High FDP/fibrinogen ratio on arrival is a predictor of 28-day mortality and the requirement for massive transfusion in severe trauma.

  17. Level Shifts and Inelastic Electron Scattering in Dense Plasmas

    DTIC Science & Technology

    1981-12-10

    similar ionized emitters are much smaller or zero. 4 iTheimer and Kepple have shown that the theory using the Debye - Huckel potential is inadequate because...the bound electrons in the Debye - I, Huckel potential. This leads to red shifts of the lines because it causes large shifts of the lower levels...V is the self-consistent potential (2) with pb O. These results are com- pared with the Debye -Ruckel theory of plasma screening, which agrees well

  18. [Preoperative digitalization. Measurement of digoxin plasma levels (author's transl)].

    PubMed

    Geiger, H J; Rietbrock, N

    1976-09-01

    In a study of 233 patients from the department of surgery and anesthesiology taking digoxin preparations 64, per cent exhibit digoxin levels in the therapeutic range (0.6--1.5 ng/ml), 19 per cent had subtoxic concentrations ranged from 1.6--2.0 ng/ml and 7 per cent were in the toxic range (greater than 2 ng/ml). In patients treated with digoxin before admission to hospital subtherapeutic levels were most frequent. An average loading dose of digoxin 1 mg or more on one day may result in subtoxic and toxic digoxin levels on the second day, in patients receiving less than 1 mg digoxin daily an increasing frequency of plasma digoxin concentrations of 1.5 ng/ml or higher values was present on the third day. Averaged plasma digoxin concentrations were correlated with daily maintenance dose. There was, however, a wide individual variation in digoxin plasma concentrations. A low incidence of toxic digoxin plasma levels was observed in patients receiving a daily oral maintenance dose of 0.375 mg digoxin (Lanicor). For prophylactic digitalization of patients with normal renal and thyroid function the following schedules or statistical guidlines are proposed: Lanicor (bioavailability 60%): oral loading dose of 0.75 mg over two days, and then daily oral maintenance dose of 0.375 mg; Novodigal (bioavailability 80%): oral loading dose of 0.6 mg over two days and then daily oral maintenance dose of 0.3 mg; Digoxin i.v.: intravenous loading dose of 0.5 (0.4) mg over two days and then 0.25 (0.2) mg daily intravenous maintenance dose. For any patient needing treatment with digitalis glycosides therapy must be individual and dynamic. The reasons for toxic concentrations were frequently attributed to wrong dosage.

  19. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    PubMed

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients.

  20. Decreased Plasma BDNF Levels of Patients with Somatization Disorder

    PubMed Central

    Kang, Nam-In; Park, Jong-Il

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. Methods The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). Results The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). Conclusion These results suggest that BDNF may play a role in the pathophysiology of somatization disorder. PMID:27757131

  1. Association of plasma lipid levels with atherosclerosis prevalence in psittaciformes.

    PubMed

    Beaufrère, Hugues; Vet, Dr Med; Cray, Carolyn; Ammersbach, Mélanie; Tully, Thomas N

    2014-09-01

    The prevalence of atherosclerosis is high in the captive psittacine population and increases with age and female sex. The genera Psittacus, Amazona, and Nymphicus are predisposed to atherosclerosis, whereas the genera Cacatua and Ara are less susceptible. Plasma cholesterol and lipoprotein abnormalities have been suggested as risk factors in the development of atherosclerosis as observed in mammals. To investigate whether the psittacine genera susceptibility to atherosclerosis and the known risk factors of age and sex could be associated with differences in the lipid profile, a retrospective analysis was conducted on blood lipid values from 5625 birds. Prevalence values were obtained from a previously published, large, case-control study and were compared with identified trends in plasma lipid profiles. Genus-specific differences were identified in plasma total cholesterol values that corresponded to observed trends in the prevalence of clinically important atherosclerotic lesions, which were also highly correlated. The effect of age was significant but was mild and may not account for the dramatic increase in atherosclerosis prevalence observed with age. In addition, Quaker parrots ( Myiopsitta monachus ), which were used as experimental models for psittacine atherosclerosis and dyslipidemia, were found to have the highest values in all lipid profile parameters. The results of this study suggest that the differences observed in prevalence among species of the psittacine genera may partly be explained by differences in plasma total cholesterol levels. Results also support the use of Quaker parrots as models for studying atherosclerosis and dyslipidemia.

  2. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    PubMed Central

    Ma, Jinhui; Guo, Wanshou; Li, Zirong; Li, Shirui; Wang, Peng

    2017-01-01

    The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH. PMID:28167850

  3. FABP4 plasma levels are increased in familial combined hyperlipidemia

    PubMed Central

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  4. Effect of fibrinogen on blood coagulation detected by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Xu, Xiangqun; Teng, Xiangshuai

    2015-05-01

    Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d1/e) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0-8 g L-1) and 2) native plasma with commercial Fbg added (0-8 g L-1). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels.

  5. Effect of fibrinogen on blood coagulation detected by optical coherence tomography.

    PubMed

    Xu, Xiangqun; Teng, Xiangshuai

    2015-05-21

    Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d1/e) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0-8 g L(-1)); and 2) native plasma with commercial Fbg added (0-8 g L(-1)). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels.

  6. Ghrelin plasma levels and appetite in peritoneal dialysis patients.

    PubMed

    Aguilera, Abelardo; Cirugeda, Antonio; Amair, Ruth; Sansone, Gabriela; Alegre, Laura; Codoceo, Rosa; Bajo, M Auxiliadora; del Peso, Gloria; Díez, Juan J; Sánchez-Tomero, José A; Selgas, Rafael

    2004-01-01

    Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (< 2600 mg/mL). Patients with anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p < 0.05), prealbumin (r = 0.51, p < 0.05), transferrin (r = 0.4, p < 0.05), growth hormone (r = 0.66, p < 0.01), NO3 (r = 0.36, p < 0.05), and eating motivation (VAS). At the same time, negative relationships were observed between blood ghrelin and GIP (r = -0.42, p < 0.05), insulin (r = -0.4, p < 0.05), leptin (r = -0.45, p < 0.05), and creatinine clearance [r = -0.33, p = 0.08 (nonsignificant)]. Ghrelin levels were not related to Kt/V or to levels of CCK and cytokines. Ghrelin plasma levels are elevated in PD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels

  7. In vivo behavior of 99mTc-fibrinogen and its potential as a thrombus-imaging agent.

    PubMed

    Harwig, S S; Harwig, J F; Coleman, R E; Welch, M J

    1976-01-01

    We have investigated the in vivo behavior of 99mTc-fibrinogen, prepared by a mild and efficient electrolytic method employing tin electrodes. The clearance mechanisms of this agent were studied, and its efficacy for imaging deep-vein thrombi in dogs with an Anger camera was determined. The 99mTc-fibrinogen preparations, which are stable in vitro, undergo partial rapid exchange of the technetium with other plasma proteins and with anions of the blood buffer system in vivo, resulting in an early drop in the percent of radioactivity associated with clottable protein. However, very little or no oxidation to pertechnetate occurs. The nonclottable material is much more rapidly cleared from the blood than the remaining 99mTc-fibrinogen, and the proportion of clottable protein activity increases with time. The fraction of 99mTc-fibrinogen that remains intact in vivo is biologically active and will incorporate into thrombi. Higher thrombus-to-blood activity ratios are obtained with 99mTc-fibrinogen than with radioidinated fibrinogen when both agents are injected into dogs 4 hr after induction of femoral vein thrombosis. Clearly delineated images of the thrombi are obtained, beginning about 2.5 hr after injection. Thus, 99mTc-fibrinogen may be of clinical use as a thrombus-imaging agent in patients under-going active thrombosis, especially in regions of high blood pool.

  8. Fibrinogen Regulates the Cytotoxicity of Mycobacterial Trehalose Dimycolate but Is Not Required for Cell Recruitment, Cytokine Response, or Control of Mycobacterial Infection▿

    PubMed Central

    Sakamoto, Kaori; Geisel, Rachel E.; Kim, Mi-Jeong; Wyatt, Bryce T.; Sellers, Llewelyn B.; Smiley, Stephen T.; Cooper, Andrea M.; Russell, David G.; Rhoades, Elizabeth R.

    2010-01-01

    During inflammatory responses and wound healing, the conversion of soluble fibrinogen to fibrin, an insoluble extracellular matrix, long has been assumed to create a scaffold for the migration of leukocytes and fibroblasts. Previous studies concluded that fibrinogen is a necessary cofactor for mycobacterial trehalose 6,6′-dimycolate-induced responses, because trehalose dimycolate-coated beads, to which fibrinogen was adsorbed, were more inflammatory than those to which other plasma proteins were adsorbed. Herein, we investigate roles for fibrin(ogen) in an in vivo model of mycobacterial granuloma formation and in infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. In wild-type mice, the subcutaneous injection of trehalose dimycolate-coated polystyrene microspheres, suspended within Matrigel, elicited a pyogranulomatous response during the course of 12 days. In fibrinogen-deficient mice, neutrophils were recruited but a more suppurative lesion developed, with the marked degradation and disintegration of the matrix. Compared to that in wild-type mice, the early formation of granulation tissue in fibrinogen-deficient mice was edematous, hypocellular, and disorganized. These deficiencies were complemented by the addition of exogenous fibrinogen. The absence of fibrinogen had no effect on cell recruitment or cytokine production in response to trehalose dimycolate, nor was there a difference in lung histopathology or overall bacterial burden in mice infected with Mycobacterium tuberculosis. In this model, fibrin(ogen) was not required for cell recruitment, cytokine response, or response to infection, but it promoted granulation tissue formation and suppressed leukocyte necrosis. PMID:20028811

  9. Plasma-cortisol levels in experimental heatstroke in dogs

    NASA Astrophysics Data System (ADS)

    Assia, Ehud; Epstein, Yoram; Magazanik, Avraham; Shapiro, Yair; Sohar, Ezra

    1989-06-01

    The effect of external heat-load, exercise and dehydration on dynamic changes in plasma cortisol during the development of heatstroke was investigated. Thirty-three unanesthetized dogs were tested under two sets of climatic conditions: comfort conditions and hot-dry climatic conditions, half of them while exercising. Half of the dogs in each group were rehydrated. None of the dogs that were investigated at room temperature suffered heatstroke. Of the dogs exposed to high ambient temperature, all of the exercising, as well as five out of six non-hydrated dogs and one rehydrated non-exercising dog suffered heatstroke. Significant dehydration (6% 7% of body weight), occurred only under hgh ambient temperature. Plasma cortisol levels of all dogs that suffered heatstroke rose conspicuously for at least 5 h and returned to normal levels 24 h later. Cortisol levels of dogs who did not experience heatstroke remained within the normal range. Cortisol levels correlated with the severity of the stress leading to heatstroke. High and rising levels of cortisol, several hours after body temperature returns to normal, may support the diagnosis of heatstroke.

  10. Plasma endothelin level in the acute stage of Bell palsy.

    PubMed

    Ikeda, M; Iijima, M; Kukimoto, N; Kuga, M

    1996-08-01

    To determine the plasma endothelin level in the acute stage in patients with Bell palsy (based on the hypothesis that endothelin, which is a potent vasoconstrictor, may play a role in the mechanism of the onset of facial nerve paralysis and in view of the fact that the etiology of Bell palsy is still a maze of unknowns). The study involved 62 patients with the acute stage (tested within 10 days of onset) of Bell palsy (i.e., idiopathic acute peripheral facial paralysis) and an additional 36 healthy persons who served as control subjects. To determine the content of endothelin, 2 ml of plasma samples was collected from each subject. Endothelin-1 was extracted and analyzed by a radioimmunoassay by using anti-endothelin-1 antibody. Nihon University Itabashi Hospital, a referral and institutional center in Tokyo, Japan. The patients who were suffering from Bell palsy exhibited a statistically significant (P < .01) increase in the endothelin level compared with that in the 36 normal control subjects. An age-matched comparison (ranges, 20-29 years and 30-39 years) of patients with Bell palsy with normal control subjects revealed a significant difference between the normal group and the group with Bell palsy in the plasma endothelin level for both age groups that were tested (P < .01). The mean value of the endothelin level in patients with Bell palsy was maximal on day 5, and the percentage of patients with abnormally elevated endothelin levels was 100% from days 6 to 9. Endothelin, which has potent vasoconstrictive effects, may contribute to the pathogenesis of the microcirculatory impairment that occurs in patients with Bell palsy, mainly by promoting secondary ischemia.

  11. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment.

    PubMed

    Mangialasche, Francesca; Xu, Weili; Kivipelto, Miia; Costanzi, Emanuela; Ercolani, Sara; Pigliautile, Martina; Cecchetti, Roberta; Baglioni, Mauro; Simmons, Andrew; Soininen, Hilkka; Tsolaki, Magda; Kloszewska, Iwona; Vellas, Bruno; Lovestone, Simon; Mecocci, Patrizia

    2012-10-01

    Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Enhanced bacterial adhesion on surfaces pretreated with fibrinogen and fibronectin

    SciTech Connect

    Mohammad, S.F.; Topham, N.S.; Burns, G.L.; Olsen, D.B.

    1988-07-01

    The effect of certain plasma proteins on the adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis on polyurethane, polyvinylchloride, or glass was investigated. Test surfaces were treated with serum, plasma, albumin, immunoglobulin G, fibrinogen, or fibronectin. Using a specially designed test chamber, surfaces previously treated with test proteins were incubated with bacterial suspension. During the experiment, the test chamber was placed on a rotator to prevent settling of bacteria. At the end of the experiment, each test well was rinsed repeatedly to remove non-adherent bacteria. The number of bacteria adherent to the test surfaces was quantitated by a combination of methods including microscopic counting of cells, scintillation counting and autoradiography. It was noted that a greater number of bacteria adhered to surfaces coated with fibrinogen or fibronectin whereas surfaces treated with serum showed reduced bacterial adhesion. The inhibitory effect of serum appeared more pronounced with S. epidermidis when compared with P. aeruginosa under identical experimental conditions. Scanning electron microscopy revealed that adherent bacteria were randomly distributed on the test surfaces and appeared to replicate while still adherent. These observations suggested that bacterial adhesion to biomaterials can be significantly influenced by the composition of the adsorbed proteins at the interface.

  13. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes: III. Shear and extrinsic fibrinogen-dependent effects.

    PubMed

    Goldsmith, H L; Frojmovic, M M; Braovac, S; McIntosh, F; Wong, T

    1994-01-01

    The effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23 degrees C was studied using a previously described double infusion technique and resistive particle counter size analysis. Using suspensions of multiple-centrifuged and -washed cells in Tyrodes-albumin [3 x 10(5) microliters-1; (17)] with [fibrinogen] from 0 to 1.2 microM, the rate and extent of aggregation with 0.7 microM ADP in Tyrodes-albumin were measured over a range of mean transit times from 0.2 to 43 s, and at mean tube shear rates, G, = 41.9, 335 and 1,335 s-1. As measured by the decrease in singlet concentration, aggregation at 1.2 microM fibrinogen increased with increasing G up to 1,335 s-1, in contrast to that previously reported in citrated plasma, in which aggregation reached a maximum at G = 335 s-1. Without added fibrinogen, there was no aggregation at G = 41.9 s-1; at G = 335 s-1, there was significant aggregation but with an initial lag time, aggregation increasing further at G = 1,335 s-1. Without added fibrinogen, aggregation was abolished at all G upon incubation with the hexapeptide GRGDSP, but was almost unaffected by addition of an F(ab')2 fragment of an antibody to human fibrinogen. Aggregation in the absence of added fibrinogen was also observed at 37 degrees C. The activation of the multiple-washed platelets was tested using flow cytometry with the fluorescently labelled monoclonal antibodies FITC-PAC1 and FITC-9F9. It was shown that 57% of single cells in unactivated PRT expressed maximal GPIIb-IIIa fibrinogen receptors (MoAb PAC1) and 54% expressed pre-bound fibrinogen (MoAb 9F9), with further increases on ADP activation. However, incubation with GRGDSP and the F(ab')2 fragment did not inhibit the prebound fibrinogen. Moreover, relatively unactivated cells (8% expressing receptor, 14% prebound fibrinogen), prepared from acidified cPRP by single centrifugation with 50 nM of

  14. Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.

    PubMed

    Riddle, M A; Jatlow, P I; Anderson, G M; Cho, S C; Hardin, M T; Cohen, D J; Leckman, J F

    1989-06-01

    Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

  15. Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Marchi, E; Torella, R

    1989-12-01

    The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

  16. [The role of post-translational modification of fibrinogen in the pathogenesis of thrombosis].

    PubMed

    Tadeusiewicz, Justyna; Nowak, Paweł

    2015-02-01

    Fibrinogen is a precursor of fibrin, which is the main component of the blood clot. The opposite of coagulation is fibrinolysis. The proper functioning of both systems allow to maintain a hemostasis. Increasing level of fibrinogen is an important risk factor for myocardial infarction or ischemic stroke. Reactive oxygen, nitrogen and chlorine species are created in inflammatory conditions, ischemia and tissues reperfusion. They can modify the fibrinogen molecule. The most important changes are associated with nitration and chlorination of tyrosine residues, oxidation of methionine, histidine and tryptophan residues, as well as formation dityrosine and carbonyl groups. Moreover, structure of fibrinogen is modified by glycation and homocysteinylation in hyperglycemia and hyperhomocysteinemia conditions. Non-enzymatic posttranslational modifications of fibrinogen contribute to formation of thrombogenic fibrin structure. The degree of fibrinogen modification is responsible for fiber structure, packing and susceptibility of fibrin clots to fibrinolysis. Additionally, the viscoelastic properties are changed. Resistance to fibrinolysis is largely associated with the modification of lysine residues in the protein molecule. Each of these alternations may contribute to increased risk of arterial and venous thrombosis.

  17. Plasma matrix metalloproteinase 2 levels and breast cancer risk.

    PubMed

    Aroner, Sarah A; Rosner, Bernard A; Tamimi, Rulla M; Tworoger, Shelley S; Baur, Nadja; Joos, Thomas O; Hankinson, Susan E

    2015-06-01

    Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000-2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study.

  18. Effect of Fibrinogen on Platelet Reactivity Measured by the VerifyNow P2Y12 Assay.

    PubMed

    Dobrovolsky, A B; Laguta, P S; Guskova, E V; Yarovaya, E B; Titaeva, E V; Storozhilova, A N; Panchenko, E P

    2016-05-01

    The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = -63.3 × dFg - 27.1 (r = -0.924, p < 0.0005) and dPRU = -54.4 × dFg - 21.8 (r = -0.764, p < 0.0005). Thus, the results of our experiments suggest that: (i) blood fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy.

  19. Association of serum calcium concentrations with fibrinogen and homocysteine in nondiabetic Korean subjects.

    PubMed

    Cho, Hyun Sun; Lee, Sung Won; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun; Kim, Eun Sook

    2016-06-01

    Considerable evidence shows that increased serum calcium levels are associated with metabolic disorders, cardiovascular disease, and increased mortality. This study investigated whether serum calcium, within a normal range, is significantly associated with serum fibrinogen and homocysteine, markers of increased cardiovascular disease risk in nondiabetic Korean subjects.A cross-sectional analysis was performed on 1096 subjects (mean age, 55.1 ± 11.1 years; 36.1% women) undergoing a general health checkup. Serum biochemistry was analyzed including serum albumin-corrected calcium (Cac), insulin resistance (IR, using homeostasis model assessment [HOMA]), fibrinogen, and homocysteine.Compared with patients within the lowest Cac quartile, those with higher Cac levels had increased fibrinogen and homocysteine levels as well as an increased proportion of smoking, dyslipidemia, and HOMA-IR. Correlation analyses revealed linear relationships for Cac with fibrinogen and homocysteine in both genders. After adjustment for confounding factors, serum Cac was significantly associated with high fibrinogen (odds ratio [OR] for the highest vs the lowest quartile = 1.76, 95% confidence interval [CI] = 1.09-2.83, P = 0.02) and homocysteine (OR = 1.83, 95% CI = 1.07-3.11, P = 0.027). Multivariate regression models showed that Cac was linearly associated with fibrinogen (standardized β = 0.14, P < 0.001) and homocysteine (standardized β = 0.07, P = 0.009).High normal calcium concentrations were independently associated with increased levels of fibrinogen and homocysteine. Further investigation is needed to validate whether slightly increased calcium levels within the normal range indicate a higher risk of cardiovascular disease.

  20. Interactions of immunoglobulin G, fibrinogen and fibronectin with Staphylococcus hyicus and Staphylococcus intermedius.

    PubMed

    Lämmler, C; de Freitas, J C; Chhatwal, G S; Blobel, H

    1985-10-01

    Binding of immunoglobulin G, fibrinogen and fibronectin to 112 cultures of coagulase-positive staphylococci together with 7 of coagulase-negative S. hyicus subsp. chromogenes were investigated. Of the coagulase-positive staphylococcal cultures 45 were S. hyicus subsp. hyicus, 51 S. intermedius and 16 S. aureus. All 45 S. hyicus subsp. hyicus cultures coagulated plasma preparations from pigs and not always those from sheep, rabbits and dogs. Labelled IgG was bound by all cultures of S. hyicus subsp. hyicus and S. aureus, but only by 6 of 51 S. intermedius cultures. Fibrinogen interacted with 28 of the 45 S. hyicus subsp. hyicus cultures, with 17 of the 51 S. intermedius cultures and with S. aureus throughout. Fibronectin reacted with 19 cultures of S. hyicus subsp. hyicus, 11 of S. intermedius and all S. aureus. The binding activities for labelled IgG were more pronounced than those for fibrinogen and fibronectin. None of the 7 cultures of S. hyicus subsp. chromogenes bound any of these plasma proteins. Bindings of fibrinogen and fibronectin to S. hyicus subsp. hyicus and S. intermedius elicited only in part distinct clumping reactions of the staphylococci in the respective plasma proteins.

  1. Spatially selective surface platforms for binding fibrinogen prepared by particle lithography with organosilanes.

    PubMed

    Englade-Franklin, Lauren E; Saner, Chamarra K; Garno, Jayne C

    2013-06-06

    We introduce an approach based on particle lithography to prepare spatially selective surface platforms of organosilanes that are suitable for nanoscale studies of protein binding. Particle lithography was applied for patterning fibrinogen, a plasma protein that has a major role in the clotting cascade for blood coagulation and wound healing. Surface nanopatterns of mercaptosilanes were designed as sites for the attachment of fibrinogen within a protein-resistant matrix of 2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG-silane). Preparing site-selective surfaces was problematic in our studies, because of the self-reactive properties of PEG-organosilanes. Certain organosilanes presenting hydroxyl head groups will cross react to form mixed surface multi-layers. We developed a clever strategy with particle lithography using masks of silica mesospheres to protect small, discrete regions of the surface from cross reactions. Images acquired with atomic force microscopy (AFM) disclose that fibrinogen attached primarily to the surface areas presenting thiol head groups, which were surrounded by PEG-silane. The activity for binding anti-fibrinogen was further evaluated using ex situ AFM studies, confirming that after immobilization the fibrinogen nanopatterns retained capacity for binding immunoglobulin G. Studies with AFM provide advantages of achieving nanoscale resolution for detecting surface changes during steps of biochemical surface reactions, without requiring chemical modification of proteins or fluorescent labels.

  2. Spatially selective surface platforms for binding fibrinogen prepared by particle lithography with organosilanes

    PubMed Central

    Englade-Franklin, Lauren E.; Saner, ChaMarra K.; Garno, Jayne C.

    2013-01-01

    We introduce an approach based on particle lithography to prepare spatially selective surface platforms of organosilanes that are suitable for nanoscale studies of protein binding. Particle lithography was applied for patterning fibrinogen, a plasma protein that has a major role in the clotting cascade for blood coagulation and wound healing. Surface nanopatterns of mercaptosilanes were designed as sites for the attachment of fibrinogen within a protein-resistant matrix of 2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG-silane). Preparing site-selective surfaces was problematic in our studies, because of the self-reactive properties of PEG-organosilanes. Certain organosilanes presenting hydroxyl head groups will cross react to form mixed surface multi-layers. We developed a clever strategy with particle lithography using masks of silica mesospheres to protect small, discrete regions of the surface from cross reactions. Images acquired with atomic force microscopy (AFM) disclose that fibrinogen attached primarily to the surface areas presenting thiol head groups, which were surrounded by PEG-silane. The activity for binding anti-fibrinogen was further evaluated using ex situ AFM studies, confirming that after immobilization the fibrinogen nanopatterns retained capacity for binding immunoglobulin G. Studies with AFM provide advantages of achieving nanoscale resolution for detecting surface changes during steps of biochemical surface reactions, without requiring chemical modification of proteins or fluorescent labels. PMID:24427541

  3. Three German fibrinogen Aalpha-chain amyloidosis patients with the p.Glu526Val mutation.

    PubMed

    Eriksson, Magdalena; Schönland, Stefan; Bergner, Raoul; Hegenbart, Ute; Lohse, Peter; Schmidt, Hartmut; Röcken, Christoph

    2008-07-01

    Plasma protein fibrinogen variants cause fibrinogen A alpha-chain (AFib) amyloidosis, which presents with hypertension, proteinuria, and azotemia. Six AFib mutations have been reported thus far. We identified three patients who presented with marked proteinuria and serum creatinine elevations. Their kidney biopsies revealed destruction of the glomerular architecture by amyloid deposits with typical, apple-green birefringence in polarized light after Congo red staining. We found immunoreactivity against fibrinogen, which is typical for this type of amyloidosis. We sequenced the FGA exon 5 and demonstrated heterozygosity for the p.Glu526Val mutation in all three cases. This amino acid substitution is the most common fibrinogen A alpha-chain variant causing AFib amyloidosis. The mutation has been reported in individuals of European and American descent but not yet in German patients. AFib amyloidosis should therefore be considered an important differential diagnosis in German patients with renal amyloidosis. In the cases described here, the use of antibodies directed against fibrinogen, followed by direct gene sequencing, revealed the underlying cause.

  4. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation

    PubMed Central

    Davalos, Dimitrios; Kyu Ryu, Jae; Merlini, Mario; Baeten, Kim M.; Le Moan, Natacha; Petersen, Mark A.; Deerinck, Thomas J.; Smirnoff, Dimitri S.; Bedard, Catherine; Hakozaki, Hiroyuki; Gonias Murray, Sara; Ling, Jennie B.; Lassmann, Hans; Degen, Jay L.; Ellisman, Mark H.; Akassoglou, Katerina

    2012-01-01

    Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease. PMID:23187627

  5. Associations of overall sitting time and TV viewing time with fibrinogen and C reactive protein: the AusDiab study.

    PubMed

    Howard, Bethany J; Balkau, Beverley; Thorp, Alicia A; Magliano, Dianna J; Shaw, Jonathan E; Owen, Neville; Dunstan, David W

    2015-02-01

    Sedentary behaviour is associated with increased risk for all-cause and cardiovascular mortality. Plasma fibrinogen and C reactive protein (CRP)-key inflammatory and/or haemostatic markers-may contribute to this association; however, few studies have examined their relationships with sedentary behaviours. We examined associations of overall sitting and TV viewing time with fibrinogen and high-sensitivity CRP (hsCRP). Plasma fibrinogen and hsCRP were measured in 3086 Australian adults (mean age: 55±12 years) who participated in the 2004-2005 AusDiab (Australian Diabetes, Obesity and Lifestyle) study. Multiple linear regression analyses examined cross-sectional associations of self-reported overall sitting and TV viewing time (h/day) with plasma fibrinogen and hsCRP, adjusting for sociodemographic, behavioural and medical treatments and conditions as potential covariates. Overall sitting time and TV viewing time were positively associated with plasma fibrinogen (sitting: β: 0.02 g/L, 95% CI (0.01 to 0.02); TV time: 0.03 g/L (0.02 to 0.05)) and hsCRP (sitting: 2.4% (1.2% to 3.6%); TV time: 4.5% (1.7% to 7.4%)). Associations were independent of leisure-time physical activity, but after adjusting for waist circumference, they remained for fibrinogen, but for hsCRP were attenuated to the null. Interactions were observed for gender×TV (p=0.011) with fibrinogen (associations in women only) and for waist circumference×TV (p=0.084) with hsCRP (associations in low-risk only). Overall sitting time was positively associated with plasma fibrinogen and hsCRP in men and women; associations of TV viewing time with fibrinogen were observed in women only. Abdominal adiposity-mediated associations for hsCRP but not for fibrinogen. Prospective and intervention studies are needed to establish likely causality and elucidate potential mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Urokinase has direct catalytic activity against fibrinogen and renders it less clottable by thrombin.

    PubMed Central

    Weitz, J I; Leslie, B

    1990-01-01

    Recently, we demonstrated that tissue plasminogen activator directly releases fibrinopeptides A and B (FPA and FPB) from fibrinogen. The purpose of this study was to determine whether urokinase has similar activity. Incubation of urokinase with fibrinogen or heparinized plasma results in concentration-dependent FPB release unaccompanied by FPA cleavage. For equivalent amidolytic activity, high molecular weight urokinase releases twofold more FPB than the low molecular weight species. In contrast, prourokinase does not release FPB until activated to urokinase. Contaminating thrombin or plasma is not responsible for urokinase-mediated FPB release because this activity is unaccompanied by FPA or B beta 1-42 cleavage, and is unaffected by heparin, hirudin, a monospecific antibody against thrombin, aprotinin, or alpha 2-antiplasmin. FPB release reflects a direct action of urokinase on fibrinogen because release is completely inhibited by a monospecific antibody against the enzyme. Further, urokinase releases FPB from the FPB-containing substrate B beta 1-42, thus confirming its specificity for the B beta 14 (Arg)-B beta 15 (Gly) bond. In addition to FPB release, SDS-PAGE analysis of the time course of urokinase-mediated fibrinogenolysis indicates progressive proteolysis of both the A alpha- and B beta-chains of fibrinogen that occurs after FPB release is completed. As a consequence of urokinase-mediated fibrinogenolysis, there is progressive prolongation of the thrombin clotting time. These studies indicate that urokinase has direct catalytic activity against fibrinogen. By releasing FPB, a potent chemoattractant, and by rendering fibrinogen less clottable by thrombin, urokinase may participate in processes extending beyond fibrinolysis. Images PMID:2365816

  7. Plasma levels of endothelin-1 and thrombomodulin in burn patients.

    PubMed

    Nakae, H; Endo, S; Inada, K; Yamada, Y; Takakuwa, T; Yoshida, M

    1996-12-01

    Plasma concentrations of endothelin-1 (ET-1) and thrombomodulin (TM) were determined in patients with burns to examine their relation to the severity of illness. Tumor necrosis factor-alpha (TNF-alpha) was also measured, and its relationship to ET-1 and TM determined. Twenty-three burn patients were evaluated, who had a total burn surface area (TBSA) of at least 20 per cent. ET-1 was measured by radioimmunoassay (RIA). TM and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA). Both the ET-1 and TM concentrations were significantly higher in the patients who developed sepsis than in those who did not and in the patients who eventually died than in those who survived. Maximum plasma concentrations of ET-1 and TM were significantly correlated with the acute physiological and chronic health evaluation II score. There was also a significant correlation between the plasma levels of TNF-alpha and both ET-1 and TM. ET-1 and TM closely reflect the severity of illness in patients with burns in the infectious stage; TNF-alpha may be involved in the production of ET-1 and TM.

  8. Multi-level molecular modelling for plasma medicine

    NASA Astrophysics Data System (ADS)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

    2016-02-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

  9. A central role for intermolecular dityrosine cross-linking of fibrinogen in high molecular weight advanced oxidation protein product (AOPP) formation.

    PubMed

    Colombo, Graziano; Clerici, Marco; Giustarini, Daniela; Portinaro, Nicola; Badalamenti, Salvatore; Rossi, Ranieri; Milzani, Aldo; Dalle-Donne, Isabella

    2015-01-01

    Advanced oxidation protein products (AOPPs) are dityrosine cross-linked and carbonyl-containing protein products formed by the reaction of plasma proteins with chlorinated oxidants, such as hypochlorous acid (HOCl). Most studies consider human serum albumin (HSA) as the main protein responsible for AOPP formation, although the molecular composition of AOPPs has not yet been elucidated. Here, we investigated the relative contribution of HSA and fibrinogen to generation of AOPPs. AOPP formation was explored by SDS-PAGE, under both reducing and non-reducing conditions, as well as by analytical gel filtration HPLC coupled to fluorescence detection to determine dityrosine and pentosidine formation. Following exposure to different concentrations of HOCl, HSA resulted to be carbonylated but did not form dityrosine cross-linked high molecular weight aggregates. Differently, incubation of fibrinogen or HSA/fibrinogen mixtures with HOCl at concentrations higher than 150 μM induced the formation of pentosidine and high molecular weight (HMW)-AOPPs (>200 k Da), resulting from intermolecular dityrosine cross-linking. Dityrosine fluorescence increased in parallel with increasing HMW-AOPP formation and increasing fibrinogen concentration in HSA/fibrinogen mixtures exposed to HOCl. This conclusion is corroborated by experiments where dityrosine fluorescence was measured in HOCl-treated human plasma samples containing physiological or supra-physiological fibrinogen concentrations or selectively depleted of fibrinogen, which highlighted that fibrinogen is responsible for the highest fluorescence from dityrosine. A central role for intermolecular dityrosine cross-linking of fibrinogen in HMW-AOPP formation is shown. These results highlight that oxidized fibrinogen, instead of HSA, is the key protein for intermolecular dityrosine formation in human plasma. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Glucose plasma levels and pregnancy outcomes in women with HIV.

    PubMed

    Meloni, Alessandra; Floridia, Marco; Alberico, Salvatore; Tamburrini, Enrica; Pinnetti, Carmela; Bucceri, Anna; Masuelli, Giulia; Viganò, Alessandra; Liuzzi, Giuseppina; Antoni, Anna Degli; Guaraldi, Giovanni; Spinillo, Arsenio; Marocco, Raffaella; Dalzero, Serena; Ravizza, Marina

    2011-01-01

    There is limited information on the relation between glucose levels in pregnancy and adverse perinatal outcomes in HIV-infected pregnant women. To evaluate the potential impact of fasting glucose levels on pregnancy outcomes in a large sample of pregnant women with HIV from a national study, adjusting for potential confounders. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. The main outcomes evaluated in univariate and multivariable analyses were birthweight for gestational age>90th percentile (large for gestational age [LGA]), nonelective cesarean delivery, and preterm delivery. Glucose measurements were considered both as continuous and as categorical variables, following the HAPO study definition. Overall, 1,032 cases were eligible for the analysis. In multivariable analyses, a birthweight>90th percentile was associated with increasing fasting plasma glucose levels (adjusted odds ratio [AOR] per unitary (mg/dL) increase, 1.04; 95% CI, 1.01-1.06; P=.005), a higher body mass index, and parity of 1 or higher. A lower risk of LGA was associated with smoking and African ethnicity. A higher fasting plasma glucose category was significantly associated with LGA occurrence, and AORs for the glucose categories of 90-94 mg/ dL and 95-99 mg/dL were 3.34 (95% CI, 1.09-10.22) and 6.26 (95% CI, 1.82-21.58), respectively. Fasting plasma glucose showed no association with nonelective cesarean section [OR per unitary increase, 1.00; 95% CI, 0.98-1.02] or preterm delivery [OR per unitary increase, 1.00; 95% CI, 0.99-1.02]. In pregnant women with HIV, glucose values below the threshold usually defining hyperglycemia are associated with an increased risk of delivering LGA infants. Other conditions may independently contribute to adverse perinatal outcomes in women with HIV and should be considered to identify pregnancies at risk.

  11. Plasma bupivacaine levels associated with extradural anaesthesia for caesarean section.

    PubMed

    Thompson, E M; Wilson, C M; Moore, J; McClean, E

    1985-05-01

    Plasma bupivacaine levels were measured in 47 women undergoing extradural Caesarean delivery. They were divided into four groups according to the following dose regimens using 0.5% bupivacaine. Group A were given a bolus of 20 ml with increment after 20 minutes. Groups B and C were given 10 ml initially with further increments if required at 10 minutes (group B) and 20 minutes (group C); Group D consisted of patients who had an extradural block extended for emergency Caesarean delivery. In the elective groups the highest and most rapidly achieved values were associated with group A and the lowest levels found in group C. The highest levels of all were found in the emergency group. The investigation indicates that slow controlled induction of extradural anaesthesia for Caesarean section greatly reduces the risk of local anaesthetic toxicity.

  12. HETEROGENEITY IN PLASMA HOMOVANILLIC ACID LEVELS IN SCHIZOPHRENIFORM DISORDER

    PubMed Central

    Pradhan, N.; Harihar, C.; Das, P.; Andrade, C.

    1992-01-01

    Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia ‘on medication’ and 17 cases of schizophrenia ‘off medication’. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics. PMID:21776112

  13. Heterogeneity in plasma homovanillic Acid levels in schizophreniform disorder.

    PubMed

    Pradhan, N; Harihar, C; Das, P; Andrade, C

    1992-04-01

    Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia 'on medication' and 17 cases of schizophrenia 'off medication'. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics.

  14. Antimullerian Hormone Level and Endometrioma Ablation Using Plasma Energy

    PubMed Central

    Bubenheim, Michael; Auber, Mathieu; Marpeau, Loïc; Puscasiu, Lucian

    2014-01-01

    Objective: To investigate the impact of ovarian endometrioma vaporization using plasma energy on antimullerian hormone (AMH) level. Method: We report a prospective, noncomparative series (NCT01596985). Twenty-two patients with unilateral ovarian endometriomas ≥30 mm, with no surgical antecedent and no ongoing pregnancy, underwent vaporization of ovarian endometriomas using plasma energy during the period of November 29, 2010 to November 28, 2012. We assessed AMH levels before surgery, 3 months postoperatively, and at the end of follow-up. Results: The mean length of postoperative follow-up was 18.2 ± 8 months. AMH level significantly varied through the 3 assessments performed in the study, as the mean values ± SD were 3.9 ± 2.6 ng/mL before the surgery, 2.3 ± 1.1 ng/mL at 3 months, and 3.1 ± 2.2 ng/mL at the end of the follow-up (P = .001). There was a significant increase from 3 months postoperatively to the end of follow-up (median change 0.7 ng/mL, P = .01). Seventy-one percent of patients had an AMH level >2 ng/mL at the end of the follow-up versus 76% before the surgery (P = 1). During the postoperative follow-up, 11 patients tried to conceive, of whom 8 (73%) became pregnant. Conclusions: The ablation of unilateral endometriomas is followed in a majority of cases by a significant decrease in AMH level 3 months after surgery. In subsequent months, this level progressively increases, raising questions about the real factors that impact postoperative ovarian AMH production. PMID:25392649

  15. Albumin and fibrinogen levels’ relation with orthopedics traumatic patients’ outcome after massive transfusion

    PubMed Central

    Bazavar, Mohammadreza; Tabrizi, Ali; Abedini, Naghi; Elmi, Asghar

    2014-01-01

    Background: Severe bleeding is common during limb trauma. It can lead to hemorrhagic shock required to massive blood transfusion. Coagulopathy is the major complication of massive transfusion-induced increased mortality rate. Aim of this study was evaluation of fibrinogen and albumin levels association with orthopedics traumatic patients’ outcome who received massive transfusion. Methods: In a cross sectional study, 23 patients with severe limb injury admitted to orthopedic emergency department were studied. All the patients received massive transfusion, that is, >10 unit blood. Albumin and fibrinogen levels are measured at admission and 24 h later, and compared according to final outcome. Results: Twenty-three traumatic patients with severe limb injuries were studied, out of which ten (43.2%) died and 13 (56.8%) were alive. There was significant difference between patients outcome in fibrinogen level after 24 h, but no difference was observed in albumin levels. Based on regression model, fibrinogen after 24 h had a significant role in determining the final outcome in traumatic patients who received massive transfusion (odds ratio 0.48, 95% confidence interval 0.15–0.92, P = 0.02). Conclusions: According to our results, fibrinogen level is the most important factor in determination of orthopedics traumatic patients when received massive transfusion. However, serum albumin does not play any role in patients’ outcome. PMID:24665235

  16. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

    PubMed Central

    Ikeda, Y; Handa, M; Kawano, K; Kamata, T; Murata, M; Araki, Y; Anbo, H; Kawai, Y; Watanabe, K; Itagaki, I

    1991-01-01

    Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]o is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis. PMID:2010539

  17. Thrombocytopenia in cirrhosis: Impact of fibrinogen on bleeding risk

    PubMed Central

    Thakrar, Sonali V; Mallett, Susan V

    2017-01-01

    AIM To investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODS A 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 (< 1200 mL returned) were analysed. All data analyses were conducted using IBM SPSS Statistics version 23. RESULTS Of 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of < 80 g/L. One hundred and fourteen (46.3%) were classified into the excessive transfusion group, 132 (53.7%) in the no excessive transfusion group. Mean age and gender distribution were similar in both groups. Baseline Hb (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 < 50 × 109/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. CONCLUSION Platelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more

  18. Heritability of plasma neopterin levels in the Old Order Amish.

    PubMed

    Raheja, Uttam K; Fuchs, Dietmar; Lowry, Christopher A; Stephens, Sarah H; Pavlovich, Mary A; Mohyuddin, Hira; Yousufi, Hassaan; Ryan, Kathleen A; O'Connell, Jeff; Brenner, Lisa A; Punzalan, Cecile; Hoisington, Andrew J; Nijjar, Gursharon K; Groer, Maureen; Shuldiner, Alan R; Pollin, Toni I; Stiller, John W; Mitchell, Braxton D; Postolache, Teodor T

    2017-06-15

    We examined the heritability of neopterin, a biomarker for cell-mediated immunity and oxidative stress, and potentially for psychiatric disorders, in the Old Order Amish. Plasma neopterin levels were determined in 2015 Old Order Amish adults. Quantitative genetic procedures were used to estimate heritability of neopterin. Heritability of log-neopterin was estimated at 0.07 after adjusting for age, gender, and household (p=0.03). The shared household effect was 0.06 (p<0.02). We found a low heritability of neopterin and small household effect, suggesting that non-household environmental factors are more important determinants of variance of neopterin levels in the Amish. Copyright © 2017. Published by Elsevier B.V.

  19. [Levels of plasma cholinesterase in Colombian working-class populations].

    PubMed

    Carmona-Fonseca, Jaime

    2003-12-01

    Levels of plasma cholinesterase in Colombian working-class populations Reference values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian populations. A representative sample of a working-class population was used to establish these values to provide reference data for use by the social security system. Two working-class populations were sampled from the Aburrá Valley (Aburrá) and eastern Antioquia (Oriente). Cholinesterase activity was measured in 827 workers, with ages spanning 18-49 years, 415 from Aburrá and 412 people from Oriente. Three methods were used to measure cholinesterase: Michel, EQM and Monotest The average values by Michel and EQM were not statistically different between regions (Michel: Aburrá, 1.11, and East, 1.13 deltas pH/hora; EQM: Aburrá, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively; p = 0 .012). By region and technique, men had significantly higher enzymatic levels than women. Within both regions and sexes, no statistically significant difference among the three aged groups was noted. Our obtained Colombian values differed significantly from foreign reference values: Michel and Monotest levels were higher and EQM levels were lower. For making clinical and epidemiologic decisions in Colombia related to these data, the values obtained for the Colombian populations are preferred over values derived from external sources.

  20. Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children.

    PubMed

    Viitasalo, A; Ågren, J; Venäläinen, T; Pihlajamäki, J; Jääskeläinen, J; Korkmaz, A; Atalay, M; Lakka, T A

    2016-08-01

    Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. This cross-sectional study included pre-pubertal children (388 normal weight children and 55 overweight/obese children); 6-9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme-linked immunosorbent assay. Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (β = 0.139, P = 0.003) and phospholipids (PLs) (β = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (β = -0.130, P = 0.006) and PL (β = -0.165, P < 0.001) were associated with higher plasma irisin level in the whole study group. The association of plasma FA composition with plasma irisin level was stronger among overweight/obese children compared to normal weight children. Higher proportion of γ-linolenic acid (β = 0.324, P = 0.017) and lower proportion of linoleic acid (β = -0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (β = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (β = 0.345, P = 0.012) and PL (β = 0.292, P = 0.033) and higher proportion of adrenic acid (β = 0.366, P = 0.008) and docosapentaenoic acid (β = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight

  1. DETERMINANTS OF PLASMA PARATHYROID HORMONE LEVELS IN YOUNG WOMEN

    PubMed Central

    Paik, Julie M.; Curhan, Gary C.; Forman, John P.; Taylor, Eric N.

    2011-01-01

    Purpose While the effects of calcium, phosphorus intake, and vitamin D on parathyroid hormone (PTH) have been well studied, less is known about other factors that impact PTH. Our goal was to delineate associations between demographic, dietary, and plasma factors and PTH. Methods We conducted a cross-sectional study of intact PTH among 1,288 non-black women in the Nurses Health Study II aged 33–53 with BMI < 30kg/m2 and eGFR ≥60 ml/min/1.73m2. Results Median PTH was 30.7pg/ml. After adjusting for 25-hydroxyvitamin D and other factors, PTH was 4.1pg/ml lower (95% CI −7.7 to −0.5) in women who smoked 1–14 cigarettes/day and 6.4pg/ml lower (95% CI −11.2 to −1.7) in women who smoked >15 cigarettes/day compared to non-smokers. After multivariate adjustment, women whose BMI was 27–29 kg/m2 had PTH levels 2.0pg/ml higher (95% CI 0.2–3.9) compared to BMI of 21–22 kg/m2, and women in the highest quartile of plasma phosphorus had PTH levels 4.1pg/ml lower (95% CI −5.8 to −2.4) than women in the lowest quartile. Higher vitamin A intake was independently associated with lower PTH whereas lower calcium intake, lower plasma calcium, lower plasma 25-hydroxyvitamin D, and winter blood draw were associated with higher PTH. Intakes of phosphorus, animal protein, magnesium, alcohol, and caffeine were not associated with PTH. Conclusions Factors not classically associated with calcium-phosphorus metabolism impact PTH. Additional research is needed to elucidate the mechanisms whereby smoking, vitamin A, and phosphorus affect PTH and to examine how body size and season may affect PTH independent of 25(OH)D. PMID:20631996

  2. Plasma Glucose Level Is Predictive of Serum Ammonia Level After Retrograde Occlusion of Portosystemic Shunts.

    PubMed

    Ishikawa, Tsuyoshi; Aibe, Yuki; Matsuda, Takashi; Iwamoto, Takuya; Takami, Taro; Sakaida, Isao

    2017-09-01

    The purpose of this study was to evaluate predictors of reduction in ammonia levels by occlusion of portosystemic shunts (PSS) in patients with cirrhosis. Forty-eight patients with cirrhosis (21 women, 27 men; mean age, 67.8 years) with PSS underwent balloon-occluded retrograde transvenous obliteration (BRTO) at one institution between February 2008 and June 2014. The causes of cirrhosis were hepatitis B in one case, hepatitis C in 20 cases, alcohol in 15 cases, nonalcoholic steatohepatitis in eight cases, and other conditions in four cases. The Child-Pugh classes were A in 24 cases, B in 23 cases, and C in one case. The indication for BRTO was gastric varices in 40 cases and hepatic encephalopathy in eight cases. Testing was conducted before and 1 month after the procedure. Statistical analyses were performed to identify predictors of a clinically significant decline in ammonia levels after BRTO. Occlusion of PSS resulted in a clinically significant decrease in ammonia levels accompanied by increased portal venous flow and improved Child-Pugh score. Univariate analyses showed that a reduction in ammonia levels due to BRTO was significantly related to lower plasma glucose levels, higher RBC counts, and higher hemoglobin concentration before the treatment. Furthermore, multivariate logistic regression identified preoperative plasma glucose level as the strongest independent predictor of a significant ammonia reduction in response to BRTO. In addition, although BRTO resulted in significantly declined ammonia levels in patients with normal glucose tolerance before the procedure, ammonia levels were not significantly decreased after shunt occlusion in patients with diabetes mellitus or impaired glucose tolerance before BRTO, according to 75-g oral glucose tolerance test results. Preoperative plasma glucose level is a useful predictor of clinically significant ammonia reduction resulting from occlusion of PSS in patients with cirrhosis. Even if PSS are present, control

  3. Fibrinogen adsorption onto 316L stainless steel under polarized conditions.

    PubMed

    Gettens, Robert T T; Gilbert, Jeremy L

    2008-04-01

    Adsorption of the plasma protein fibrinogen onto electrically polarized 316L stainless steel was observed and quantified using both in situ and ex situ atomic force microscopy (AFM) techniques. Significant differences in fibrinogen adsorption were observed across voltages. Ex situ studies showed significantly lower area coverage (theta) and height of adsorbed Fb on cathodically polarized surfaces when compared to anodically polarized surfaces. Conformational differences in the protein may explain the distinctions in Fb surface area coverage (theta) and height between the anodic and cathodic cases. In situ studies showed significantly slower kinetics of Fb adsorption onto surfaces below -100 mV (vs. Ag/AgCl) compared to surfaces polarized above -100 mV. Electrochemical current density data showed large charge transfer processes (approximately 1 x 10(-5) to 1 x 10(-4) A/cm(2)) taking place on the 316L SS surfaces at voltages below -100 mV (vs. Ag/AgCl). These relatively large current densities point to flux of ionic species away from the surface as a major source of the reduction in adsorption kinetics rather than just hydrophilic or electrostatic effects.

  4. Thrombospondin interaction with fibrinogen. Evidence for binding to the A alpha- and B beta-chains of fibrinogen.

    PubMed

    Bacon-Baguley, T; Kudryk, B J; Walz, D A

    1987-02-15

    Platelet thrombospondin interacts with fibrinogen in a specific and saturable manner. Thrombospondin was found to specifically bind to the A alpha- and B beta-chains of fibrinogen; binding was independent of divalent ions. Binding could be blocked either by preincubation of thrombospondin with 9.4 microM fibrinogen or by preincubation of fibrinogen with 1.1 nM thrombospondin. Thrombospondin bound only to the beta-chain component of the D and DD plasmin fragment of fibrinogen. Thrombospondin interaction with fibrinogen was not blocked by preincubation with synthetic peptides which have previously been identified as either the fibrinogen receptor (alpha 572-575, the synthetic tetrapeptide arginyl-glycyl-aspartyl-serine) or cell attachment (gamma 400-411) domains. Fibrinogen, therefore, possesses at least two unique and distinct sites, within the A alpha- and B beta-chains, for its interaction with thrombospondin.

  5. Are fibrinogen and complete blood count parameters predictive in incarcerated abdominal hernia repair?

    PubMed

    Kahramanca, Sahin; Kaya, Oskay; Ozgehan, Gulay; Guzel, Hakan; Azili, Cem; Gokce, Emre; Kucukpinar, Tevfik; Kulacoglu, Hakan

    2014-01-01

    Therapeutic delays in cases of external incarcerated hernias typically result in increasing morbidity, mortality, and health expenditures. We investigated the diagnostic role of blood fibrinogen level, white blood count (WBC), mean platelet volume (MPV), and platelet distribution width (PDW) in patients with incarcerated hernia. Two groups, each containing 100 patients, were studied. Group A underwent elective, and group B underwent incarcerated and urgent external hernia repair. We observed high fibrinogen and WBC levels but low MPV and PDW values for patients in group B. Contrary to our expectations, we found lower MPV and PDW values in the complicated group than in the elective group. The morbidity rate and cost burden were higher in group B, and the results were statistically significant. Early operation should be recommended for patients with incarcerated external hernias if their fibrinogen and WBC levels are high.

  6. Repeated quantitative measurements of De Novo synthesis of albumin and fibrinogen

    PubMed Central

    Rooyackers, Olav; Klaude, Maria; Hebert, Christina; Wernerman, Jan; Norberg, Åke

    2017-01-01

    The possibility of using two different isotopomers, for the incorporation of isotopically labeled amino acids, was explored to enable longitudinal studies of de novo synthesis of two export liver proteins, albumin and fibrinogen. The agreement of the synthesis rates between the two different labels was evaluated along with the reproducibility of repeated experiments using different time intervals. Healthy volunteers were studied in a standardized fed state. Protocol A (n = 10) involved two measurements 48 hours apart. Protocol B (n = 6) involved three measurements at baseline and five hours and then seven days after the initial measurement. De novo synthesis of albumin and fibrinogen by the incorporation of D5-phenylalanine or D8-phenylalanine were measured using the flooding dose technique. Albumin and fibrinogen were isolated from plasma using standard techniques. Fractional and absolute synthesis rates were calculated. Repeated measurements employing the two isotoptomers showed good agreement for albumin fractional synthesis rate after 48 hours (p = 0.92) and after 7 days (p = 0.99), with a coefficient of variation of 5.9% when using the same isotopic label. For fibrinogen, the coefficient of variation for the fractional synthesis rate employing the same isotopic label was 16.6%. Repeated measurements after 48 hours and seven days showed less agreement although there was no statistical difference (P = 0.32 and P = 0.30 respectively). Repeated measurement after five hours showed a statistical significant difference for the fractional synthesis rate of fibrinogen (p = 0.008) but not for albumin (p = 0.12). Repeated measurements of albumin de novo synthesis more than 48 hours apart show acceptable agreement using either one or two different isotopic labels. For fibrinogen the larger intra-individual scatter necessitates larger study groups to detect changes in longitudinal studies. Repeated measurements within 48 hours need to be validated further. PMID:28350862

  7. Role of Fibrinogen and Protease-Activated Receptors in Acute Xenobiotic-Induced Cholestatic Liver Injury

    PubMed Central

    Luyendyk, James P.; Mackman, Nigel; Sullivan, Bradley P.

    2011-01-01

    Alpha-naphthylisothiocyanate (ANIT)–induced cholestatic liver injury causes tissue factor (TF)–dependent coagulation in mice, and TF deficiency reduces ANIT-induced liver injury. However, the mechanism whereby TF contributes to hepatotoxicity in this model is not known. Utilizing pharmacological and genetic strategies, we evaluated the contribution of fibrinogen and two distinct receptors for thrombin, protease-activated receptor-1 (PAR-1) and PAR-4, in a model of acute ANIT hepatotoxicity. ANIT administration (60 mg/kg, po) caused a marked induction of the genes encoding the three fibrinogen chains (α, β, and γ) in liver, an increase in plasma fibrinogen, and concurrent deposition of thrombin-cleaved fibrin in liver. Partial depletion of circulating fibrinogen with ancrod did not impact ANIT hepatotoxicity. However, complete fibrin(ogen) deficiency significantly reduced serum alanine aminotransferase activity and hepatocellular necrosis in ANIT-treated mice. ANIT-induced hepatocellular necrosis was similar in PAR-1−/− mice compared with PAR-1+/+ mice. Interestingly, the progression of ANIT-induced hepatocellular necrosis was significantly reduced in PAR-4−/− mice and by administration of an inhibitory PAR-4 pepducin (P4Pal-10, 0.5 mg/kg, sc) to wild-type mice 8 h after ANIT treatment. Interestingly, a distinct lesion, parenchymal-type peliosis, was also observed in PAR-4−/− mice treated with ANIT and in mice that were given P4Pal-10 prior to ANIT administration. The results suggest that fibrin(ogen), but not PAR-1, contributes to the progression of ANIT hepatotoxicity in mice. Moreover, the data suggest a dual role for PAR-4 in ANIT hepatotoxicity, both mediating an early protection against peliosis and contributing to the progression of hepatocellular necrosis. PMID:20974703

  8. Fib420: a normal human variant of fibrinogen with two extended alpha chains.

    PubMed Central

    Fu, Y; Grieninger, G

    1994-01-01

    In fibrinogen, alpha E chains form a subpopulation of alpha subunits that are distinguished by a carboxyl extension homologous to the C termini of the other two constituent chains: beta and gamma. The molecular mass of alpha E is > 50% greater than that of the common alpha subunit, due in part to an extra 236 amino acids. These residues are encoded by exon VI, a recently discovered extension of the fibrinogen alpha gene. Additional mass is contributed by posttranslational processing, including N-glycosylation, which, based on experiments with the inhibitor tunicamycin, was found to account in large measure for alpha E migration on SDS/PAGE at approximately 110 kDa rather than at its calculated mass of 92,843 Da. An antibody specific for the exon VI-encoded domain of alpha E (anti-VI) and capable of recognizing alpha E-containing fibrinogen in both native and denatured form was generated using a recombinant protein as immunogen. Its use in Western blot analysis of fractions of normal human blood (plasma and preparations of fibrinogen) revealed a single, sharp, alpha E-containing band migrating behind the position of the broad, predominant fibrinogen band, (alpha beta gamma)2. Designation of the upper band as Fib420, an approximately 420-kDa homodimer of the formula (alpha E beta gamma)2, is based on the overwhelming proportion of alpha E subunits (> 80% of the total alpha chains) found in anti-VI-immunoprecipitable material from hepatoma cell medium. Several lines of evidence suggest that the alpha E subunit, alone or incorporated into fibrinogen, is more stable than the common alpha chain, a feature of potential clinical importance. Images PMID:8146165

  9. Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

    PubMed

    Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Berg, Anders H; Geahchan, Carl; Wenger, Julia B; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2016-07-01

    Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median

  10. The role of cardiorespiratory fitness on plasma lipid levels.

    PubMed

    Parto, Parham; Lavie, Carl J; Swift, Damon; Sui, Xuemei

    2015-11-01

    Dyslipidemia is a treatable risk factor for cardiovascular disease. Epidemiological studies have demonstrated the importance of treatment for abnormalities in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. Aside from pharmacotherapy, exercise and cardio-respiratory fitness have been shown to have beneficial effects on decreasing cardiovascular disease risk. Even though previous data regarding the benefits of exercise on plasma lipids have been somewhat conflicting, numerous studies have demonstrated that exercise increases HDL-cholesterol and reduces the triglyceride levels. Also, smaller, more atherogenic LDL particles seem to decrease with increases in cardio-respiratory fitness and exercise, and favorable blood lipid profiles seem to persist longer through the adult life span.

  11. [Plasma taurine levels in patients with esophagus cancer].

    PubMed

    Lamônica-Garcia, Vânia Cristina; Marin, Flávia Andréa; Lerco, Mauro Masson; Moreto, Fernando; Henry, Maria Aparecida Coelho Arruda; Burini, Roberto Carlos

    2008-01-01

    The esophagus cancer-host has a two way close relationship as seen in its sulphur-amino acid metabolism. Taurine one of these compounds has ubiquous role in host defense and other physiological mechanisms related to survival. To study the plasma levels of taurine and its precursors in patients with esophagus cancer. In a sectional design both groups, patients (n = 16, 43-73 yrs old) and healthy controls (n = 20, 27-65 yrs old) were assessed for anthropometry, body-weight lost, hematology (Hb, Ht, total leukocytes and lymphocyte counts), general biochemistry (albumin, glucose, lipids and aminotransferases) and chromatographic analysis for taurine, cysteine, and homocysteine. The survival time was registered there since from the clinical-histopathological diagnosis. All participants had a written ethical consent for the research. The cancer patients were predominantly, white males of low social economic class, with spinocellular carcinoma stage IV located at upper 3rd half of them presented hypoalbuminemia and 16% referred significant body-weight loss. The patients showed statistically lower values of Hb, Ht, total and HDL cholesterol and cysteine and significantly higher values of taurine, homocysteine and aminotransferases than healthy controls. A positive relationship was found between taurine and either TLC (r = 0.50) and survival (r = 0.81). Lower plasma cysteine along with higher levels of taurine and homocysteine and the positive direct association of taurine with indications of survival suggest an effective role of this compound and therefore a prospective special nutritional care in its precursors (cysteine, methionine and B vitamins) of these patients.

  12. CGRP and ET-1 plasma levels in normal subjects.

    PubMed

    Parlapiano, C; Paoletti, V; Campana, E; Giovanniello, T; Pantone, P; Labbadia, G; Califano, F; Donnarumma, L; Musca, A

    1999-01-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide displaying about 50% homology with amylin which is secreted from the pancreatic islets of Langerhans. The main form, the beta-CGRP, is produced by the enteric nervous system and perivascular nerves of the vasa-vasorum. It represents one of the most powerful vasodilator yet discovered but its role is not yet completely clarified. High levels of this peptide have been shown in patients affected with thyroid medullary carcinoma, phaemocromocytoma and lung carcinoma. Recently circulating levels of CGRP have been found in normal subjects. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, isolated from porcine endothelial cells, is an important regulator of the vascular tone acting in physiological antagonism with atrial natriuretic hormone (ANH). With this study we intended to investigate the presence of any correlation between CGRP and ET-1 in normal subjects. For the study we considered 20 normal subjects (11 males and 9 females) aged 23 to 50. Plasma levels of CGRP and ET-1 were measured by radioimmunological Kit. A positive and significant correlation between calcitonin gene-related peptide and endothelin-1 was found. Our results confirms that CGRP and ET-1 have opposing actions on vessels and that they can act together in haemodinamic regulation.

  13. Pentaerythritol tetranicotinate (niceritrol) decreases plasma lipoprotein(a) levels.

    PubMed

    Tanaka, K; Hayashi, K; Shingu, T; Kuga, Y; Okura, Y; Yasunobu, Y; Ohtani, H; Nomura, S; Kurushima, H; Saeki, M; Kambe, M; Kajiyama, G

    1997-04-01

    We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

  14. Predelivery maternal fibrinogen as a predictor of blood loss after vaginal delivery.

    PubMed

    Niepraschk-von Dollen, Katja; Bamberg, Christian; Henkelmann, Anne; Mickley, Laura; Kaufner, Lutz; Henrich, Wolfgang; Pauly, Franziska

    2016-10-01

    The present study investigated whether fibrinogen level during the first stage of labor is associated with bleeding severity in the third stage of labor. We prospectively enrolled 1019 pregnant women with planned vaginal delivery. Upon admission to delivery, maternal fibrinogen levels, hemoglobin content, and coagulation parameters were evaluated. Blood loss in the third stage of labor was systematically measured using a calibrated collecting drape. Univariate and multivariate analyses were performed to identify predictors of PPH (blood loss ≥500 mL) and S-PPH (blood loss ≥1000 mL). Among 809 vaginal deliveries, mean maternal predelivery fibrinogen was 4.65 ± 0.77 g/L, PPH incidence was 12 %, S-PPH incidence was 3.5 %, and median blood loss was 250 mL. Fibrinogen levels were significantly lower in women with S-PPH (4.22 ± 0.82 g/L) than without S-PPH (4.67 ± 0.75 g/L; p = 0.004), but did not significantly differ between women with PPH (4.67 ± 0.84 g/L) and those without PPH (4.67 ± 0.75 g/L; p = 0.985). Instrumental delivery and predelivery fibrinogen levels were independent predictors of S-PPH. Primiparous status, birth weight >4000 g, genital tract laceration, episiotomy and instrumental delivery were independent predictors of PPH. For each 1 g/L increase of predelivery fibrinogen level, the risk of S-PPH after vaginal delivery decreases by a factor of 0.405 (95 % CI 0.219-0.750; p = 0.004).

  15. Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model.

    PubMed

    Zentai, Christian; Solomon, Cristina; van der Meijden, Paola E J; Spronk, Henri M H; Schnabel, Jonas; Rossaint, Rolf; Grottke, Oliver

    2016-11-01

    In a 24-hour porcine model of liver injury, we showed that fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis. Here we report data from the same study showing the impact of fibrinogen on coagulation variables. Coagulopathy was induced in 20 German land race pigs by hemodilution and blunt liver injury. Animals randomly received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters were assessed and thromboelastometry (ROTEM) was performed. Fibrinogen concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM clot formation time, and prothrombin time induced by hemodilution and liver injury. A decrease in clot strength was also ameliorated. Endogenous thrombin potential was significantly higher in the fibrinogen group than in the control group, 20 minutes (353 ± 24 vs 289 ± 22 nmol/L·min; P < .05) and 100 minutes (315 ± 40 vs 263 ± 38 nmol/L·min; P < .05) after the start of infusion. However, no significant between-group differences were seen in other thrombin generation parameters or in d-dimer or thrombin-antithrombin levels. Fibrinogen-platelet binding was reduced following liver injury, with no significant differences between groups. No significant between-group differences were observed in any parameter at ∼12 and ∼24 hours. This study suggests that, in trauma, fibrinogen supplementation may shorten some measurements of the speed of coagulation initiation and produce a short-lived increase in endogenous thrombin potential, potentially through increased clotting substrate availability. Approximately 12 and 24 hours after starting fibrinogen concentrate/saline infusion, all parameters measured in this study were comparable in the 2 study groups. © The Author(s) 2015.

  16. Fibrinogen and associated risk factors in a high-risk population: urban Indigenous Australians, the DRUID Study.

    PubMed

    Maple-Brown, Louise J; Cunningham, Joan; Nandi, Nirjhar; Hodge, Allison; O'Dea, Kerin

    2010-10-29

    Epidemiological evidence suggests that fibrinogen and CRP are associated with coronary heart disease risk. High CRP in Indigenous Australians has been reported in previous studies including our 'Diabetes and Related diseases in Urban Indigenous population in Darwin region' (DRUID) Study. We studied levels of fibrinogen and its cross-sectional relationship with traditional and non-traditional cardiovascular risk factors in an urban Indigenous Australian cohort. Fibrinogen data were available from 287 males and 628 females (aged ≥ 15 years) from the DRUID study. Analysis was performed for associations with the following risk factors: diabetes, HbA1c, age, BMI, waist circumference, waist-hip ratio, total cholesterol, triglyceride, HDL cholesterol, C-reactive protein, homocysteine, blood pressure, heart rate, urine ACR, smoking status, alcohol abstinence. Fibrinogen generally increased with age in both genders; levels by age group were higher than those previously reported in other populations, including Native Americans. Fibrinogen was higher in those with than without diabetes (4.24 vs 3.56 g/L, p < 0.001). After adjusting for age and sex, the following were significantly associated with fibrinogen: BMI, waist, waist-hip ratio, systolic blood pressure, heart rate, fasting triglycerides, HDL cholesterol, HbA1c, CRP, ACR and alcohol abstinence. On multivariate regression (age and sex-adjusted) CRP and HbA1c were significant independent predictors of fibrinogen, explaining 27% of its variance; CRP alone explained 25% of fibrinogen variance. On factor analysis, both CRP and fibrinogen clustered with obesity in women (this factor explained 20% of variance); but in men, CRP clustered with obesity (factor explained 18% of variance) whilst fibrinogen clustered with HbA1c and urine ACR (factor explained 13% of variance). Fibrinogen is associated with traditional and non-traditional cardiovascular risk factors in this urban Indigenous cohort and may be a useful biomarker of

  17. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats.

    PubMed

    Bjørndal, Bodil; Ramsvik, Marie S; Lindquist, Carine; Nordrehaug, Jan E; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K

    2015-09-08

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC's content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis.

  18. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  19. Optical tweezers study of red blood cell aggregation and disaggregation in plasma and protein solutions.

    PubMed

    Lee, Kisung; Kinnunen, Matti; Khokhlova, Maria D; Lyubin, Evgeny V; Priezzhev, Alexander V; Meglinski, Igor; Fedyanin, Andrey A

    2016-03-01

    Kinetics of optical tweezers (OT)-induced spontaneous aggregation and disaggregation of red blood cells (RBCs) were studied at the level of cell doublets to assess RBC interaction mechanics. Measurements were performed under in vitro conditions in plasma and fibrinogen and fibrinogen + albumin solutions. The RBC spontaneous aggregation kinetics was found to exhibit different behavior depending on the cell environment. In contrast, the RBC disaggregation kinetics was similar in all solutions qualitatively and quantitatively, demonstrating a significant contribution of the studied proteins to the process. The impact of the study on assessing RBC interaction mechanics and the protein contribution to the reversible RBC aggregation process is discussed.

  20. Optical tweezers study of red blood cell aggregation and disaggregation in plasma and protein solutions

    NASA Astrophysics Data System (ADS)

    Lee, Kisung; Kinnunen, Matti; Khokhlova, Maria D.; Lyubin, Evgeny V.; Priezzhev, Alexander V.; Meglinski, Igor; Fedyanin, Andrey A.

    2016-03-01

    Kinetics of optical tweezers (OT)-induced spontaneous aggregation and disaggregation of red blood cells (RBCs) were studied at the level of cell doublets to assess RBC interaction mechanics. Measurements were performed under in vitro conditions in plasma and fibrinogen and fibrinogen + albumin solutions. The RBC spontaneous aggregation kinetics was found to exhibit different behavior depending on the cell environment. In contrast, the RBC disaggregation kinetics was similar in all solutions qualitatively and quantitatively, demonstrating a significant contribution of the studied proteins to the process. The impact of the study on assessing RBC interaction mechanics and the protein contribution to the reversible RBC aggregation process is discussed.

  1. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    NASA Technical Reports Server (NTRS)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  2. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    NASA Technical Reports Server (NTRS)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  3. Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases

    NASA Astrophysics Data System (ADS)

    Marucco, Arianna; Fenoglio, Ivana; Turci, Francesco; Fubini, Bice

    2013-04-01

    TiO2 nanoparticles (NPs) are contained in different kinds of industrial products including paints, self-cleaning glasses, sunscreens. TiO2 is also employed in photocatalysis and it has been proposed for waste water treatment. Micrometric TiO2 is generally considered a safe material, while there is concern on the possible health effects of nanometric titania. Due to their small size NPs may migrate within the human body possibly entering in the blood stream. Therefore studies on the interaction of NPs with plasma proteins are needed. In fact, the interaction with proteins is believed to ultimately influences the NPs biological fate. Fibrinogen and albumin are two of the most abundant plasma proteins. They are involved in several important physiological functions. Furthermore, fibrinogen is known to trigger platelet adhesion and inflammation. For these reasons the study of the interaction between these protein and nanoparticles is an important step toward the understanding of the behavior of NPs in the body. In this study we investigated the interaction of albumin and fibrinogen with TiO2 nanoparticles of different crystal phases (rutile and anatase) using an integrated set of techniques. The amount of adsorbed fibrinogen and albumin for each TiO2 surface was investigated by using the bicinchoninic acid assay (BCA). The variation of the surface charge of the NP-protein conjugates respect to the naked NPs was used to indirectly estimate both surface coverage and reversibility of the adsorption upon dilution. Surface charge was monitored by measuring the ζ potential with a conventional electrophoretic light scattering (ELS) system. The extent of protein deformation was evaluated by Raman Spectroscopy. We found that both proteins adsorb irreversibly against electrostatic repulsion, likely undergoing conformational changes or selective orientation upon adsorption. The size of primary particles and the particles aggregation rather than the crystal phase modulate the

  4. The fibrinogen antigenic turbidimetric assay (FIATA): the X2x test--the corrected chi-square comparison against the control-mean.

    PubMed

    Stief, Thomas W

    2007-01-01

    Vancomycin precipitates fibrinogen. The turbidity induced by this vancomycin-fibrinogen interaction is used to establish a simple standardized antigenic assay for plasmatic fibrinogen, the FIATA. 1 mM vancomycin or 2 mM chloramine-T inactivates 50% of fibrinogen in human plasma. In contrast to chloramine-T, vancomycin does not react in NaJ-based photometric assay for chloramines,vancomycin does not inactivate the singlet oxygen-sensible antithrombin III, and the vancomycin action against fibrinogen is not changed in spite of the presence of the 1O2 quenchers methionine or ascorbic acid. The FIATA is performed as follows: to 25 microL plasma 50 microL PBS are added and the absorbance (A) at 405 nm is read. Then 50 microL FIATA-reagent, consisting of 4.4 mM vancomycin in PBS, are added. After 2 minutes (RT) DeltaA is determined and standardized against a plasma pool of 100% of norm (2.8 g/L) fibrinogen. The FIATA is nearly linear up to a fibrinogen concentration of about 150% of norm (4.2 g/L), resulting in a DeltaA of about 600 mA. The lower detection limit is 4% of norm (0.1 g/L). The intra-assay and interessay CV values are < 4%. The normal range of FIATA is 100% +/-20% (x- +/- 1 SD). In = 321 or 344 unselected patient plasmas the FIATA (x- = 130%; SD = 52% or 43%) correlated with the functional fibrinogen assays a) modified Clauss-Method (x- = 4.1 g/L; SD =1.7 g/L) with r = 0.755 and b) FIFTA (x- = 124%; SD = 40%) with r = 0.813. The vancomycin/fibrinogen interaction (binding of about 16 molecules of vancomycin/molecule of fibrinogen) can be used to purify fibrinogen out of plasma. Vancomycin also clouds dysfunctional fibrinogen (fibrinogen in presence of EDTA or chloramine-T)or soluble fibrin. Vancomycin-reacted fibrinogen stimulates tissue type plasminogen activator (t-PA) up to about 20-fold. The experimental data are analyzed by a new significance test: the two foldYates-corrected chi-square comparison against the mean value ofthe control-collective, called

  5. Mechanisms of fibrinogen adsorption at solid substrates.

    PubMed

    Adamczyk, Zbigniew; Barbasz, Jakub; Cieśla, Michał

    2011-06-07

    Adsorption of fibrinogen, modeled as a linear chain of touching beads of various sizes, was theoretically studied using the random sequential adsorption (RSA) model. The adsorption process was assumed to consist of two steps: (i) formation of an irreversibly bound fibrinogen monolayer under the side-on orientation, which is independent of the bulk protein concentration and (ii) formation of the reversibly bound, end-on monolayer, whose coverage was dependent on the bulk concentration. Calculation based on the RSA model showed that the maximum surface concentration of the end-on (reversible) monolayer equals N(⊥∞) = 6.13 × 10(3) μm(-2) which is much larger than the previously found value for the side-on (irreversible) monolayer, equal to N(∞) = 2.27 × 10(3) μm(-2). Hence, the maximum surface concentration of fibrinogen in both orientations is determined to be 8.40 × 10(3) μm(-2) corresponding to the protein coverage of 5.70 mg m(-2) assuming 20% hydration. Additionally, the surface blocking function (ASF) was determined for the end-on fibrinogen adsorption, approximated for the entire range of coverage by the interpolating polynomial. For the coverage approaching the jamming limit, the surface blocking function (ASF) was shown to vanish proportionally to (θ(⊥∞) - θ(⊥))(2). These calculation allowed one to theoretically predict adsorption isotherms for the end-on regime of fibrinogen and adsorption kinetics under various transport conditions (diffusion and convection). Using these theoretical results, a quantitative interpretation of experimental data obtained by TIRF and ellipsometry was successfully performed. The equilibrium adsorption constant for the end-on adsorption regime was found to be 8.04 × 10(-3) m. On the basis of this value, the depth of the adsorption energy minimum, equal to -17.4 kT, was predicted, which corresponds to ΔG = -41.8 kJ mol(-1). This is in accordance with adsorption energy derived as the sum of the van der Waals

  6. A survey of surface hemorheological experiments on the inhibition of fibrinogenin formation employing surface layers of fibrinogen systems with heparins and other substances. A contribution on antithrombogenic action.

    PubMed

    Copley, A L; King, R G

    1984-08-01

    In earlier studies using a modified Weissenberg Rheogoniometer, we found decreased rigidity or torque values (tau) in surface layers of heparin plasma, when compared to tau of oxalate plasma from the same blood withdrawal (Thrombosis Res. 1, 1-17, 1972). In subsequent studies of the viscoelasticity of surface layers of highly purified fibrinogen (97-100% clottability) of human and bovine origin, we found, with some heparins, marked lowering of surface viscous moduli (eta's) and of surface elastic moduli (Gs). With some heparins no changes in tau, eta's and Gs occurred. Certain low molecular weight (LMW) preparations of heparins showed decreases, but some did not. This is also the case with heparins of low and high affinity for antithrombin. Calcium heparin and Ca2+ alone always increased eta's and Gs, when added to the fibrinogen system. N-desulfated heparin both decreased or did not change eta's and Gs. Preparations of fibrinogen in dog plasma, to which sodium heparin was added, resulted in a decrease of tau values. These results appear to emphasize that plasma proteins other than fibrinogen, and other plasma constituents, may affect surface hemorheological values. These findings suggest needed interface studies of fibrinogen systems to which plasma or plasma constituents are added. We found also that other substances, i.e., dextran MW 20,000; dextran sulfate MW 17,000; sodium hyaluronate and depolymerized hyaluronate decreased tau, eta's and Gs markedly. Recent findings in the literature are discussed in relation to thrombogenesis in which fibrinogenin gelation is considered as the initial phase of blood clotting. Fibrinogenin is the new term for initial fibrinogen aggregation and subsequent fibrinogen gelation without thrombin participation. The inhibition of fibrinogenin formation extra vivum is considered to be a valid indicator of antithrombogenic activity of substances which play a significant role in investigations on the therapy and prevention of

  7. A fibrinogen-based precision microporous scaffold for tissue engineering.

    PubMed

    Linnes, Michael P; Ratner, Buddy D; Giachelli, Cecilia M

    2007-12-01

    Fibrin has been long used as an effective scaffolding material to grow a variety of cells and tissue constructs. It has been utilized mainly as a hydrogel in varying concentrations to provide an environment in which suspended cells work to rearrange the fibers and lay down their own extracellular matrix. For these fibrin hydrogels to be useful in many tissue-engineering applications, the gels must be cultured for long periods of time in order to increase their mechanical strength to the levels of native tissues. High concentrations of fibrinogen increase the mechanical strength of fibrin hydrogels, but at the same time reduce the ability of cells within the scaffold to spread and survive. We present a method to create a microporous, nanofibriliar fibrin scaffold that has controllable pore size, porosity, and microstructure for applications in tissue engineering. Fibrin has numerous advantages as a scaffolding material as it is normally used by the body as temporary scaffolding for tissue regeneration and healing, and can be autologously sourced. We present here a scaffolding process which enhances the mechanical properties of the fibrin hydrogel by forming it surrounding poly(methyl-methacrylate) beads, then removing the beads with acetone to form an interconnected microporous network. The acetone serves the dual purpose of precipitating and fixing the fibrinogen-based scaffolds as well as adding strength to the network during polymer bead removal. Effects of fibrinogen concentration and time in acetone were examined as well as polymerization with thrombin. A natural crosslinker, genipin, was also used to add strength to the scaffolds, producing a Young's modulus of up to 184+/-5 kPa after 36 h of reaction. Using these methods we were able to produce microporous fibrin scaffolds that support cell growth and have mechanical properties similar to many native tissues.

  8. Fibrinogen metabolism in patients with spinal cord injury.

    PubMed

    Frisbie, James H

    2006-01-01

    Deep venous thrombosis and pulmonary thromboembolism are common within weeks of spinal cord injury (SCI) but clinically uncommon in the chronically paralyzed. Fibrinogen half-life (FHL) and fibrin uptake of the legs (FUT), as indicators of an active thrombotic process, have been used to test this clinical impression. Data from the use of autologous preparations of radioiodinated fibrinogen to determine FHL and FUT in 17 men paralyzed at cervical (6), thoracic (10), and lumbar levels (1), at ASIA grades A (15) and C (2) in 1974 to 1976 were reviewed. Group A consisted of 12 subjects 29 +/- 8 years of age and paralyzed 1 week to 5 months (median, 1 month). Group B consisted of 5 subjects 46 +/- 17 years of age and paralyzed 24 to 96 months (median, 36 months). Group B subjects were older and paralyzed longer than Group A. Group C consisted of 4 able-bodied control subjects enrolled at the same time for FHL studies, and these subjects were 34 to 38 years of age. FHL was 61 +/- 14 hours for all SCI subjects and 95 +/- 23 hours for Group C (P = 0.001). Group A FHL was 59 +/- 16 hours, and FUT was positive in 8 of 12 subjects. Group B FHL was 66 +/- 7 hours, and FUT was positive in 3 of 4 subjects (1 FUT not done; P = 0.30 and 1.0, respectively). Fibrinogen metabolism was abnormal in patients with acute SCI at high risk for pulmonary thromboembolism (PE) but continued to be abnormal beyond the high risk period for PE, possibly because of the greater age of the patients in the long-term paralysis group.

  9. Brief Report: Plasma Beta-Endorphin and Cortisol Levels in Autistic Patients.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; And Others

    1991-01-01

    Comparison of plasma levels of beta-endorphin (BE) found that levels in 8 adult autistic patients were lower than levels in 17 healthy controls, for both morning and evening measurements. Plasma BE concentrations were also significantly lower for 13 developmentally disabled patients than levels for normal controls. (JDD)

  10. Brief Report: Plasma Beta-Endorphin and Cortisol Levels in Autistic Patients.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; And Others

    1991-01-01

    Comparison of plasma levels of beta-endorphin (BE) found that levels in 8 adult autistic patients were lower than levels in 17 healthy controls, for both morning and evening measurements. Plasma BE concentrations were also significantly lower for 13 developmentally disabled patients than levels for normal controls. (JDD)

  11. Current-level triggered plasma-opening switch

    DOEpatents

    Mendel, C.W.

    1987-06-29

    An opening switch for very high power electrical pulses uses a slow magnetic field to confine a plasma across a gap between two electrodes. The plasma conducts the electric pulse across the gap while the switch is closed. A magnetic field generated by the pulse repels the slow magnetic field from the negative electrode to push the plasma from the electrode, opening the switch. A plurality of radial vanes may be used to enhance the slow magnetic field. 5 figs.

  12. Current-level triggered plasma-opening switch

    DOEpatents

    Mendel, Clifford W.

    1989-01-01

    An opening switch for very high power electrical pulses uses a slow magnetic field to confine a plasma across a gap between two electrodes. The plasma conducts the electric pulse across the gap while the switch is closed. A magnetic field generated by the pulse repels the slow magnetic field from the negative electrode to push the plasma from the electrode, opening the switch. A plurality of radial vanes may be used to enhance the slow magnetic field.

  13. Associations between dietary acrylamide intake and plasma sex hormone levels

    PubMed Central

    Hogervorst, Janneke G.; Fortner, Renee T.; Mucci, Lorelei A.; Tworoger, Shelley S.; Eliassen, A. Heather; Hankinson, Susan E.; Wilson, Kathryn M.

    2013-01-01

    Background The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiological studies have observed positive associations between acrylamide intake and endometrial, ovarian and breast cancer risks, which suggests that acrylamide may have sex-hormonal effects. Methods We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and SHBG among 687 postmenopausal and 1300 premenopausal controls from nested case-control studies within the Nurses’ Health Studies. Results There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin or SHBG. Among normal weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, while statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Conclusions Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biological plausibility to the observed increased risks of endometrial, ovarian and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. Impact The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. PMID:23983241

  14. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    SciTech Connect

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-23

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.

  15. Fibrinogen Availability and Coagulation Function After Hemorrhage and Resuscitation in Pigs

    DTIC Science & Technology

    2011-08-01

    partial thromboplastin time (aPTT), are per- formed in plasma, and, therefore, can- not reflect the interaction of platelet and fibrinogen. Activated ...requires a valid and comprehensive as- sessment of coagulation function. Nor- mal coagulation assays, such as pro- thrombin time (PT) and activated ...the initiation of thrombin generation by the activation of FVIIa/TF complex and FXa, the propagation of thrombin generation from the production of

  16. Caffeine suppresses β-amyloid levels in plasma and brain of Alzheimer’s transgenic mice

    PubMed Central

    Cao, Chuanhai; Cirrito, John R.; Lin, Xiaoyang; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W.; Holtzman, David M.; Potter, Huntington

    2013-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer’s Disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain β-amyloid (Aβ) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Aβ levels in both brain interstitial fluid and plasma without affecting Aβ elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Aβ, but also decreases in both soluble and deposited Aβ in hippocampus and cortex. Irrespective of caffeine treatment, plasmalevels did not correlate with brain Aβ levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Aβ1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated — both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold. First, that both plasma and brain Aβ levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD. Second, that plasmalevels are not an accurate index of brain Aβ levels/deposition or cognitive performance in aged AD mice. PMID:19581723

  17. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.

    PubMed

    Cao, Chuanhai; Cirrito, John R; Lin, Xiaoyang; Wang, Li; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W; Holtzman, David M; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.

  18. Role of Fibrinogen in Trauma Induced Coagulopathy

    DTIC Science & Technology

    2010-01-01

    indices but does not effect the changes in fibrinogen metabolism resulting from haemorrhage.11 Gelatin products also have a diluting effect and fibrin...von Willebrand factor have also been reported. Hydroxyethyl starch (HES) solutions may increase haemor- rhagic tendency, particularly solutions with a...von Willebrand type 1-like syndrome, and a fibrin polymerization disturbance that might exceed the anticoagulant effect of gelatin .13 Hyperfibrinolysis

  19. Plasma Cytokine Levels During Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2012-01-01

    Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

  20. Plasma level of atropine after accidental ingestion of Atropa belladonna.

    PubMed

    Bogan, Reinhard; Zimmermann, Thomas; Zilker, Thomas; Eyer, Florian; Thiermann, Horst

    2009-07-01

    Ingestion of toxic plant constituents still poses a challenge in clinical management. The amount of berries ingested is often unclear and in the case of Atropa belladonna may affect clinical outcome. Plasma levels of atropine may thus be useful in confirming the cause of intoxication. A 48-year-old man had ingested three handfuls of Atropa belladonna. Within 6 h he experienced phases of disorientation, aggressiveness, and tachycardia. He was initially treated with diazepam, an intravenous infusion of physostigmine and activated charcoal. After temporary improvement his clinical condition worsened and he was transferred to our toxicological intensive care unit. Here, ongoing sedation and continuous administration of physostigmine was necessary because of disorientation. In the early phase of hospitalization, a blood sample was taken and a muscarinic receptor total binding equivalent to binding of 130 microg/L atropine was determined by a radio receptor technique. Within 2 days the patient recovered completely and was discharged in a good general condition. Receptor binding may help confirm diagnosis and elucidate mechanisms in this type of exposure.

  1. Platelet fibrinogen binding in Basset Hound Hereditary Thrombopathy

    SciTech Connect

    Patterson, W.; Estry, D.; Schwartz, K.; Bell, T.

    1986-03-01

    Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10/sup -5/M ADP in the presence of /sup 125/I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of fibrinogen per platelet. The BHT platelet aggregation defect does not seem to be caused by a functionally abnormal GP IIb-IIIa complex, since BHT platelets bind normal amounts of fibrinogen. The results suggest that fibrinogen binding is not sufficient for platelet aggregation, and other factors, perhaps receptor mobility and membrane phospholipid content should be investigated in BHT.

  2. Differences in Plasma Cytokine Levels between Elite Kayakers and Nonathletes

    PubMed Central

    Borges, G. F.; Rama, L.; Pedreiro, S.; Alves, F.; Santos, A.; Massart, A.; Paiva, A.; Teixeira, A. M.

    2013-01-01

    Regular moderate exercise has been shown to have anti-inflammatory effects that help prevent several chronic diseases. However, the effects of chronic training an elite athletes have not been the focus of much research. This study aimed to determine whether there were differences in cytokine levels (IL-1β, IL-1ra, IL-6, IL-10, IL-18, IFN-γ, and TNF-α) in circulating peripheral blood (PB) between elite kayakers and nonathletes. Subjects were 13 elite male kayakers, aged 20.0 ± 3 years, with average body mass of 75.0 ± 7.9 kg and 177.3 ± 7.1 cm height and with a VO2max of 58.3 ± 7.8 mL·kg−1·min−1. The nonathletes were 7 men, aged 18.2 ± 1.1 years, body mass of 81.3 ± 13.8 kg, and 171.9 ± 4.5 cm height. Blood samples were collected after six weeks of offtraining and before the start of a new training season. PB leukocyte populations were determined by flow cytometry. Cytokine levels were quantified by ELISA. When nonathletes were compared with the kayakers, the latter exhibited lower plasma concentrations of IL-1β, IL-18, and IFN-γ as well as a lower concentration of IL-1ra. Positive correlations between IL-18 and B cells in the athletes were also found. These results seem to reinforce the anti-inflammatory role of regular training. PMID:23781501

  3. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

    PubMed Central

    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality. One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367–557) in patients with AAS and 383 U/L (IQR 331–460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37–51) and the specificity was 73% (95% CI 69–76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11–4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable

  4. Coronary sinus plasma beta endorphin levels in cardioischemic patients undergoing PTCA.

    PubMed

    Parlapiano, C; Negri, M; Tonnarini, G; Borgia, M C; Martuscelli, E; Nigri, A; Campana, E; Giovanniello, T; Pantone, P

    1998-01-01

    Plasma beta-endorphin levels were studied in the coronary sinus of 8 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). All the patients had ECG ischemic signs and pain during the inflation of the balloon. No significant changes in plasma beta-endorphin levels were observed during PTCA-induced ischemia. Baseline coronary sinus plasma beta-endorphin levels were found to be elevated when compared with peripheral ones which would suggest an accumulation of beta-endorphin in the ischemic heart.

  5. Metabonomics of Pig Blood Plasma Following Whole Body Exposure to Low Levels of Gb Vapor

    DTIC Science & Technology

    2005-10-01

    METABONOMICS OF PIG BLOOD PLASMA FOLLOWING WHOLE BODY EXPOSURE TO LOW LEVELS OF GB VAPOR Vicky L. H. Bevilacqua▲, Terrence G...DATES COVERED - 4. TITLE AND SUBTITLE Metabonomics Of Pig Blood Plasma Following Whole Body Exposure To Low Levels Of Gb Vapor 5a. CONTRACT...analysis of minipig blood plasma by high field NMR after low-level exposure to GB by whole body inhalation. EXPERIMENTAL METHODS 1. SARIN

  6. Plasma Potassium Levels in Healthy Prehypertension Subjects and the Role of A High Potassium Drink.

    PubMed

    Farapti, Farapti; Sayogo, Savitri; Siregar, Parlindungan

    2017-02-24

    Most populations around the world consume less than the recommended levels of potassium. Long term low potassium intake could lead to decreased plasma potassium levels and induce hypokalemia. The increasing of plasma potassium levels 0,2-0,4 mmol/L by improving potassium intake decreased significantly blood pressure (BP). Assessing plasma potassium levels in healthy people related to potassium intake have not been studied. In this study, we analysed plasma potassium levels in prehypertension (PHT) subjects and to evaluate the effect of tender coconut water (TCW) as a high potassium drink on plasma potassium levels in PHT adults. Thirthy-two female aged 25-44 years were randomly allocated to 14 days on TCW or water in a parallel randomized clinical trial . The treatment (T) group received TCW 300 ml twice daily and the control (C) group received water 300 ml twice daily too. At baseline, plasma potassium levels was 3.71±0.41 mmol/L, and 22.58% were categorized as hypokalemia. After 14 days treatment, potassium plasma level between T and C groups were not significantly different (p=0,247). The change of plasma potassium levels in both groups showed tendency to increase but not statistically significant (p=0.166). In healthy prehypertension women, the low levels of potassium plasma may be caused by low potassium intake for long time and intervension with TCW 300 ml twice daily for 14 consecutive days has not proven yet to increase plasma potassium levels. It is necessary to give higher dose and longer time to increase potassium plasma in low potassium plasma level subjects.

  7. Biperiden and haloperidol plasma levels and extrapyramidal side effects in schizophrenic patients.

    PubMed

    Meszaros, K; Lenzinger, E; Hornik, K; Schönbeck, G; Hatzinger, R; Langer, G; Sieghart, W; Aschauer, H N

    1997-01-01

    Anticholinergic drugs such as biperiden are used for the treatment of extrapyramidal side effects (EPS) induced by neuroleptics such as haloperidol. The effects of biperiden and haloperidol plasma levels on EPS were studied in 29 chronically ill schizophrenics. The results show relationships between biperiden dose and biperiden plasma levels (BPL), and between BPL and haloperidol plasma levels (HPL). Neither BPL nor HPL seem to influence EPS.

  8. Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains.

    PubMed

    Sabbadini, Priscila Soares; Genovez, Marcia Rocha Novais; Silva, Cecília Ferreira da; Adelino, Thelma Lúcia Novaes; Santos, Cintia Silva dos; Pereira, Gabriela Andrade; Nagao, Prescilla Emy; Dias, Alexandre Alves de Souza de Oliveira; Mattos-Guaraldi, Ana Luiza; Hirata Júnior, Raphael

    2010-08-01

    The production of fibrinous exudates may play an important role in determining the outcome of bacterial infection. Although pseudomembrane formation is a characteristic feature of diphtheria, little is known about the fibrinogen (Fbn)-binding properties of Corynebacterium diphtheriae strains and the influence of the gene that codes for diphtheria toxin (tox gene) in this process. In this study we demonstrated the ability of C. diphtheriae strains to bind to Fbn and to convert Fbn to fibrin. Bacterial interaction with rabbit plasma was evaluated by both slide and tube tests. Interaction of microorganisms with human Fbn was evaluated by both enzyme linked immunosorbent assay (ELISA) and fluorescein isothiocyanate-conjugated (FITC) Fbn binding assays. Nontoxigenic and toxigenic strains formed bacterial aggregates in the presence of plasma in the slide tests. The ability to convert Fbn to a loose web of fibrin in the plasma solution in the tube tests appeared to be a common characteristic of the species, including strains that do not carry the tox gene. Fbn binding to C. diphtheriae strains occurred at varying intensities, as demonstrated by the FITC-Fbn and ELISA binding assays. Our data suggest that the capacity to bind to Fbn and to convert Fbn to fibrin may play a role in pseudomembrane formation and act as virulence determinants of both nontoxigenic and toxigenic strains.

  9. Validated HPLC method for determination of caffeine level in human plasma using synthetic plasma: application to bioavailability studies.

    PubMed

    Alvi, Syed N; Hammami, Muhammad M

    2011-04-01

    Several high-performance liquid chromatography (HPLC) methods have been described for the determination of caffeine in human plasma. However, none have been cross validated using synthetic plasma. The present study describes a simple and reliable HPLC method for the determination of the caffeine level in human plasma. Synthetic plasma was used to construct calibration curves and quality control samples to avoid interference by caffeine commonly present in donor's human plasma. After deproteination of plasma samples with perchloric acid, caffeine and antipyrine (internal standard, IS) were separated on a Waters Atlantis C18 column using a mobile phase of 15 mM potassium phosphate (pH 3.5) and acetonitrile (83:17, v/v), and monitored by photodiode array detector, with the wavelength set at 274 nm. The relationship between caffeine concentrations and peak area ratio (caffeine-IS) was linear over the range of 0.05-20 μg/mL. Inter-run coefficient of variation was ≤ 5.4% and ≤ 6.0% and bias was ≤ 3% and ≤ 7% using human and synthetic plasma, respectively. Mean extraction recovery from human plasma of caffeine and the IS was 91% and 86%, respectively. Caffeine in human plasma was stable for at least 24 h at room temperature or 12 weeks at -20 °C, and after three freeze-thaw cycles. The method was successfully applied to monitor caffeine levels in healthy volunteers with correction of caffeine levels using the mean ratio of the slopes of the calibration's curves constructed using human and synthetic plasma.

  10. [The clinical value of measuring plasma level of very long chain fatty acids in Addison disease].

    PubMed

    Chen, Jun; Zhang, Jian; Wang, De-Xin

    2007-09-01

    To determine the level of very long chain fatty acids (VLCFA) in plasma to find out X-linked adrenoleukodystrophy (X-ALD) in patients with Addison disease. By using gas chromatography measurement of plasma levels of C(26:0), ratios of C(26:0)/C(22:0) and C(24:0)/C(22:0) was carried out in 36 patients with Addison disease. Among the 36 cases, 6 had elevated plasma VLCFA levels; thus the presence of X-ALD was confirmed. Misdiagnosis of X-ALD can be reduced by measuring plasma level of VLCFA early in male patients with Addison disease, especially in young ones.

  11. Characterization of nanobodies binding human fibrinogen selected by E. coli display.

    PubMed

    Salema, Valencio; López-Guajardo, Ana; Gutierrez, Carlos; Mencía, Mario; Fernández, Luis Ángel

    2016-09-20

    Abnormal levels of fibrinogen (Fib) in blood plasma are associated with several pathological conditions and hence methods for its detection in blood and body fluids are essential. Nanobodies (Nbs) or (VHHs) are single domain antibodies derived from camelids with excellent biophysical and antigen-binding properties, showing great promise in diagnostics and therapy. In this work, we select and characterize high affinity Nbs binding human Fib employing an E. coli cell surface display system based on the fusion of an immune library of VHH domains with the β-domain of Intimin. Bacteria displaying high-affinity Nbs against Fib were selected using magnetic cell sorting (MACS). Specific binding of the selected clones to Fib was confirmed by flow cytometry of E. coli bacteria, as well as by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) with the purified Nbs. E. coli display also provided an excellent estimation of the affinity of the selected Nbs by flow cytometry analysis under equilibrium conditions, with equilibrium constant (KD) values very similar to those obtained by SPR analysis. Finally, pairwise epitope-scouting studies revealed that the selected Nbs bound distinct epitopes on Fib. The selected Nbs are promising diagnostic tools for determination of human Fib levels.

  12. Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant

    SciTech Connect

    Liu Zhilin; Ukomadu, Chinweike

    2008-01-25

    Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.

  13. Heterogeneous surface distribution of the fibrinogen-binding protein on Candida albicans.

    PubMed Central

    Martínez, J P; López-Ribot, J L; Chaffin, W L

    1994-01-01

    As detected by indirect immunofluorescence and confocal microscopy, fibrinogen binding was heterogeneously distributed on the surface of Candida albicans. A low level of binding was generally observed homogeneously distributed on some yeast and most hyphal extensions of germ tubes. However, on most hyphal extensions, there were randomly distributed areas of increased expression, as revealed by patches of greater fluorescence intensity. Images PMID:8300229

  14. Fabrication of fibrinogen/P(LLA-CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications.

    PubMed

    He, Chuanglong; Xu, Xiaohong; Zhang, Fan; Cao, Lijun; Feng, Wei; Wang, Hongsheng; Mo, Xiumei

    2011-06-01

    Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA-CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA-CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR-FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA-CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA-CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA-CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA-CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA-CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction.

  15. Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability.

    PubMed

    Papageorgiou, Nikolaos; Briasoulis, Alexandros; Hatzis, Georgios; Androulakis, Emmanuel; Kozanitou, Maria; Miliou, Antigoni; Charakida, Marietta; Zacharia, Effimia; Papaioannou, Spyridon; Paroutoglou, Ioannis; Siasos, Gerasimos; Pallantza, Zoi; Tousoulis, Dimitris

    2017-01-01

    We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (β = 0.257 ± 18.6; P<.001), but not hypertension status (β = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (β = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Elevated 1-h post-challenge plasma glucose levels in subjects with normal glucose tolerance or impaired glucose tolerance are associated with whole blood viscosity.

    PubMed

    Marini, Maria Adelaide; Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

    2017-08-01

    It has been suggested that glucose levels ≥155 mg/dl at 1-h during an oral glucose tolerance test (OGTT) may predict development of type 2 diabetes and cardiovascular events among adults with normal glucose tolerance (NGT 1 h-high). Studies showed a link between increased blood viscosity and type 2 diabetes. However, whether blood viscosity is associated with dysglycemic conditions such as NGT 1 h-high, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) is unsettled. 1723 non-diabetic adults underwent biochemical evaluation and OGTT. A validated formula based on hematocrit and total plasma proteins was employed to estimate whole blood viscosity. Subjects were categorized into NGT with 1 h glucose <155 mg/dL (NGT-1 h-low), NGT-1 h-high, IFG and/or IGT. Hematocrit and blood viscosity values appeared significantly higher in individuals with NGT 1 h-high, IFG and/or IGT as compared to NGT 1 h-low subjects. Blood viscosity was significantly correlated with age, waist circumference, blood pressure, HbA1c, fasting, 1- and 2-h post-challenge insulin levels, total cholesterol and low-density lipoprotein, triglycerides, fibrinogen, white blood cell, and inversely correlated with high-density lipoprotein and insulin sensitivity. Of the four glycemic parameters, 1-h post-challenge glucose showed the strongest correlation with blood viscosity (β = 0.158, P < 0.0001) in a multivariate regression analysis model including several atherosclerosis risk factors. Our results demonstrate a positive relationship between blood viscosity and 1-h post-challenge plasma glucose. They also suggest that a subgroup of NGT individuals with 1-h post-challenge plasma >155 mg/dl ha