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Fibrinogen is a key coagulation protein that is necessary for the formation of stable clots. Fibrinogen levels have been reported to be one of the first to fall during major haemorrhage reflecting consumption, dilution and fibrinogenolysis. Its role in acquired major haemorrhage, both in relation to the contribution it plays to the coagulopathy of major bleeding that can exacerbate bleeding and how effective fibrinogen supplementation can be at improving clinical outcomes, has received a great deal of attention over the last 10 - 15 years. This commentary focuses on just three of the more recent publications from the last 5 years that provide some of the evidence behind how we can think about fibrinogen as a haemostatic treatment for acquired major haemorrhage and how we can use the laboratory thresholds to guide therapy.

Background/Objectives Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is important as PDAC can lead to mortality; however, no specific biomarker has been identified for its early diagnosis. We previously identified fibrinogen α chain as a promising biomarker for differentiating between patients with and without PDAC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we aimed to validate the clinical usefulness of serum fibrinogen as a biomarker for PDAC. Methods From 2009 to 2011, blood samples of 67 PDAC patients and 43 healthy adults (controls) were prospectively collected. Serum fibrinogen levels and their clinical significances were evaluated. Results Mean fibrinogen levels were significantly higher in the PDAC group than in the control group (3.08 ± 0.565 vs. 2.54 ± 0.249 log10 ng/mL, P Conclusions Serum fibrinogen levels may be a useful biomarker for diagnosing and predicting PDAC prognosis.

Background γ′ fibrinogen is an alternatively-spliced fibrinogen variant that displays different coagulation parameters in vitro than the major form of fibrinogen. Purified γ′ fibrinogen has slower clotting kinetics than unfractionated fibrinogen, but forms clots that are stronger and resistant to fibrinolysis. However, these properties have only been investigated in human populations in a limited number of studies. We therefore performed a retrospective analysis to test the hypothesis that γ′ fibrinogen levels influence coagulation in vivo. Methods In the present study, we utilized blood samples that were collected from traumatic brain injury patients to probe the relationship between γ′ fibrinogen levels and traditional coagulation parameters. Results The results show that the levels of γ′ fibrinogen were inversely associated with clotting kinetics, indicated by a shortened INR. In addition, the levels of γ′ fibrinogen were associated with stronger clots by thrombelastography. However, these changes were not associated with significant changes in hemorrhage progression. Conclusions These findings verify that γ′ fibrinogen properties observed in purified systems result in similar properties in a clinical setting, and may affect coagulation.

To retrospectively analyze the relationship between fibrinogen levels and outcomes in poor-grade aneurysmal subarachnoid hemorrhage (aSAH).We recruited 66 patients with poor-grade aSAH who were treated by neurosurgical clipping between January 2010 and December 2015. Serum samples were taken immediately on admission. Baseline information, complications, and outcomes at 6 months were recorded. Univariate and multivariate logistic regression analyses were used to explore the relationship between fibrinogen levels and clinical outcomes.Nineteen men and 47 women were included; the average age was 57.2 years. The median of the admission serum fibrinogen level was 3.3 g/L. Of the 66 patients, 18 had died by 6 months after initial hemorrhage, whereas 48 patients survived. Multivariate analyses showed that Hunt and Hess grade V (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.06-14.20; P = 0.04) and admission serum fibrinogen level2.5 g/L (OR, 6.15; 95% CI, 1.67-22.67; P = 0.006) were significantly associated with 6-month mortality. In addition, admission serum fibrinogen level was negatively correlated with delayed cerebral ischemia, and admission serum fibrinogen level2.5 g/L (OR, 3.86; 95% CI, 0.99-15.09; P = 0.05) was also significantly associated with delayed cerebral ischemia.Patients with poor-grade aSAH with reduced admission fibrinogen level have a higher risk of delayed cerebral ischemia and 6-month mortality compared with those without. The admission serum fibrinogen level might be useful as a predictor and treatment target in patients with poor-grade sSAH who have undergone surgical treatment.

Objective The ROTEM sigma whole blood viscoelastic test uses different technology than the former delta model. Existing ROTEM based algorithms use cutoff values based on the delta model, and cannot be applied to the sigma model. The authors tested sensitivity and specificity of ROTEM sigma parameters to detect specific hemostatic deficiencies and established cutoff values with the aim of developing a treatment algorithm. Design Prospective observational evaluation of diagnostic accuracy. Setting This study was performed in a tertiary center. Participants Blood samples for standard laboratory tests (SLTs) and ROTEM sigma analysis were obtained from 14 healthy volunteers and 35 patients showing various hemostatic disorders (isolated factor deficiencies, von Willebrand's disease, thrombocytopenia, hypofibrinogenemia, hyperfibrinogenemia, and patients undergoing cardiac surgery). Intervention Correlation coefficients were calculated between SLTs and ROTEM parameters in the extrinsic pathway activation, intrinsic pathway activation, and extrinsic pathway activation with platelet inhibition tests. Receiver operator characteristics defined the values of ROTEM parameters, which best predict plasma fibrinogen level measured by Clauss method 37 seconds and 1.5 times the upper normal limit. Measurement and Main Results The combination of FIBTEM A5 ≤12 mm and EXTEM A5 ≤44 mm identified a fibrinogen level 80 seconds had a 25.0% sensitivity and a 100% specificity for a PT 204 seconds showed a sensitivity of 75.0% and a specificity of 97.4% for an aPTT >37 and a sensitivity of 100% and a specificity of 80.0% for an aPTT >55 seconds. Conclusion The authors present the first ROTEM sigma-based algorithm for the treatment of coagulopathic bleeding. The algorithm uses parameters with optimal sensitivity and specificity for critical values of SLTs determined from a heterogenous group of donors.

Elevated plasma fibrinogen is associated with tumor progression and poor outcomes in several cancers. However, no studies have demonstrated the prognostic value of hyperfibrinogenemia in the setting of autologous hematopoietic stem cell transplantation (ASCT). We retrospectively reviewed 104 patients who were diagnosed with malignant lymphoma (ML) or multiple myeloma (MM) and underwent ASCT in our institution between 2007 and 2018. The patients included 63 men and 41 women with a median age of 58 years (range, 24-70 years). Forty-seven patients were diagnosed with ML, and 57 patients were diagnosed with MM. The median follow-up period was 59 months. The median pretransplant plasma fibrinogen levels were 336 mg/dL in ML patients and 320 mg/dL in MM patients. The Kaplan-Meier method revealed that patients with pretransplant hyperfibrinogenemia had a significantly shorter 5-year overall survival (OS) than those without hyperfibrinogenemia (5-year OS: 34.3% vs 81.0%, P .001). Among 27 patients with diffuse large B cell lymphoma, patients with pretransplant hyperfibrinogenemia (n = 12) had a significantly shorter OS than those without hyperfibrinogenemia (n = 15) (5-year OS: 40.0% vs 80.2%, P = .006). Among 57 MM patients, there was no significant difference in the 5-year OS between the high-fibrinogen group and the low-fibrinogen group (5-year OS: 77.1% vs 50.4%, P = .17). Our study suggested that pretransplant hyperfibrinogenemia was associated with a poor survival in patients with lymphoma who underwent ASCT. Because our results are based on a small-sized analysis, further large-scale prospective studies are warranted to verify this conclusion.

Background: We investigated the prognostic value of preoperative fibrinogen levels in hepatocellular carcinoma patients receiving liver transplantation by building a scoring model for predicting tumor recurrence. Methods: Cox regression analysis was used to identify factors that predicted tumor recurrence, and a scoring model was generated by assigning a value of 0 or 1 to each independent risk factor. The cut-off value for fibrinogen was determined by receiver operating characteristic curve analysis. Results: Preoperative fibrinogen concentration was significantly higher in patients with vs. without tumor recurrence (3.27 g/L vs. 2.34 g/L, P 400 vs. ≤400 ng/mL plasma alpha-fetoprotein concentration (3.43 g/L vs. 2.76 g/L, P = 0.007). The 5-year disease-free survival rate was significantly lower for patients with elevated (≥2.68 g/L) vs. normal (3 tumor nodules, and elevated fibrinogen concentration were independent risk factors for tumor recurrence. A scoring model based on these risk factors predicted recurrence with a sensitivity of 68.3% and a specificity of 87.5%. Conclusions: Elevated preoperative plasma fibrinogen concentration is associated with tumor recurrence in HCC patients after liver transplantation. A new scoring model predicted recurrence with good sensitivity and specificity. Keywords: Liver transplantation (LT), Hepatocellular carcinoma (HCC), Scoring model, Recurrence, Fibrinogen concentration

EssentialsBleeding in chemotherapy induced thrombocytopenia (CIT) might be influenced by hyperfibrinolysis. t-PA-thromboelastography is a fast and reliable assay for hyperfibrinolysis in CIT patients. Clots of CIT patients are more susceptible to t-PA induced lysis compared to healthy individuals. Besides platelets, other factors are likely to influence clot lysis in CIT patients. Background Bleeding events in chemotherapy-induced thrombocytopenic (CIT) patients with similar platelet counts might be influenced by changes in clot lysis potential. Objectives To investigate, in an observational study, thromboelastographic lysis parameters, alterations in clot strength and susceptibility to clot lysis in CIT patients. To identify factors associated with fibrinolytic profiles, and to evaluate the effects of platelet transfusions. Methods Independent determinants of tissue-type plasminogen activator (t-PA)-ROTEM lysis parameters were identified with multivariable linear regression. Clot formation, strength and lysis parameters were compared with the results of healthy individuals. Characteristics of CIT patients with and without hyperfibrinolytic profiles were compared. t-PA-ROTEM results before, 1 hour after and 24 hours after platelet transfusion were compared. Results A total of 72 consecutive CIT patients were included. t-PA-ROTEM lysis parameters correlated with changes in fibrinolytic proteins. Clot formation time was longer, maximum clot firmness was weaker and lysis times were shorter than in healthy individuals. CIT patients had low plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor levels, and 40% showed hyperfibrinolytic profiles. Platelet transfusions resulted in less hyperfibrinolytic profiles in many, but not all CIT patients. Patients without hyperfibrinolytic profiles had higher fibrinogen, factor VIII and alpha(2)-antiplasmin levels. Conclusions t-PA-ROTEM can be used as a fast and reliable assay to detect hyperfibrinolytic profiles in CIT patients. CIT patients have weaker clots, which are more susceptible to clot lysis, than healthy individuals. Besides platelets, other factors are likely to influence clot susceptibility to fibrinolysis in CIT patients. The impact of a hyperfibrinolytic t-PA-ROTEM profile on bleeding remains to be investigated.

Objective Adenoid cystic carcinoma (ACC) is a rare entity of salivary gland cancer. Inflammatory and hematologic markers and their prognostic and predictive value have been intensively studied in several cancer entities. The aim of this study was to investigate the role of such markers in patients with ACC. Study Design This retrospective analysis investigated hematologic and inflammatory markers in patients with ACC in the period between the years 1996 and 2016. We assessed the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, cross-reactive protein and fibrinogen levels. A total of 28 to 31 patients were included, depending on the examined parameter. All markers were evaluated for their effects on outcome and prognostic value. Results Patients with an elevated preoperative NLR (>2) had a significantly higher multiple recurrence rate (44.4% vs 8.3%; P = .049). Other hematologic markers showed no significant effects on outcome. Conclusions This study showed that the NLR may serve as a useful prognosticator for a high risk of multiple recurrences in patients with ACC.

Objective To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria. Study design MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. Results Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. Conclusions This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

Isolated fibrinogen deficiency is a particularly rare disorder in patients with normal preoperative prothrombin time/activated partial thromboplastin time. We present a case involving a 62-year-old female patient diagnosed with isolated fibrinogen deficiency following lung cancer surgery. Her preoperative prothrombin time/activated partial thromboplastin time was normal; however, both were prolonged after the surgery. The patient had spontaneous postoperative bleeding owing to presumably congenital fibrinogen deficiency. The management of spontaneous postoperative bleeding is challenging, and the serum fibrinogen level is an important factor to consider for the treatment of this condition. The cause of postoperative isolated fibrinogen deficiency could not be ascertained; nevertheless, our findings show that it is necessary to have a countermeasure for isolated fibrinogen deficiency in order to prevent any critical complications.

Objectives A number of etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and has been reported to be associated with fibrinogen. We aimed to determine whether hyperfibrinogenemia is associated with poor outcome and whether a serial change in fibrinogen level is associated with outcome. Methods Twenty-two patients with ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups classified as improved and non-improved according to improvement of hearing. Blood samples were also collected from patients who visited the emergency room with coronary heart disease (CHD) as the control group. Results Initial fibrinogen level was significantly different between the non-improved and improved ISSNHL group (350.63 ± 87.20 vs. 310.71 ± 81.06. The improved ISSNHL group showed a “surge phenomenon”, in which fibrinogen started to decrease at day 5 and increased at day 26. In the non-improved group, fibrinogen remained elevated throughout the course of therapy. Conclusion It is important to measure not only the initial fibrinogen level but also to monitor its change throughout the course of therapy in order to predict the outcome of ISSNHL.

Background: Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in China, and resulted in an ongoing pandemic. Starting at April 12, 2020, in an intent to stop the spread of the virus, Israelis were obligated to wear a face mask. Mask-wearing over the mouth and nose creates a hard-to-ventilate space which might accumulate CO2 and induce relative hypoxia, possibly facilitating substantial hematologic changes.We sought to study the association of mask wearing during the COVID-19 pandemic and hematological and obstetrical outcomes among singleton gestations. Methods: Obstetrical outcome and laboratory results of women admitted for delivery throughout the mask-wearing period were compared to those delivering during two pre-pandemic control groups- i) the parallel period in 2019 and ii) a larger cohort of pre-pandemic years (March 2011-April 2020). Findings: Overall, 1,939 women delivered during the COVID-19 pandemic. Compared with the pre-pandemic period, the mean hemoglobin and fibrinogen levels were significantly higher during the mask-wearing period [12.15±1.1 vs. 11.96±1.2, p

This large cohort study aimed to investigate the association between fibrinogen levels and 2-year all-cause mortality, and its predictive value in addition to a basic model including traditional risk factors in Chinese patients receiving the contemporary percutaneous coronary intervention (PCI). A

Objective CA-125 protein is used as a marker in clinical practice for the diagnosis of endometriomas. The aim of this study was to determine whether endometriomas are accompanied by an increased level of urocortin, ghrelin, and leptin, as well as the increased parameters of blood cell count, fibrinogen, and CA-125. Materials and methods The study included 86 women aged 18–38 years who had been treated laparoscopically for lesions in the adnexa with the characteristics of endometriomas and mature teratoma, during the period September 2009 to November 2012. The statistical analysis was performed using the nonparametric Mann–Whitney U test and the Spearman rank correlation coefficients ( p ≤ 0.05). Results The medians were 105.31 pg/mL versus 120.84 pg/mL for urocortin, 7.16 pg/mL versus 9.13 pg/mL for leptin and 584.33 pg/mL versus 657.82 pg/mL for ghrelin ( p > 0.05), respectively. Analyzing the parameters of blood cell count, statistically significant differences were shown in the respective groups for leucocyte level (5.35 × 10 9 /L vs. 6.7 × 10 9 /L; p = 0.029), fibrinogen level (3.12 mg% vs. 2.57 mg%; p = 0.001), and CA-125 (36.50 U/mL vs. 15.08 U/mL; p = 0.001). Conclusion In conclusion, the prognostic values for CA-125, leukocytes, and fibrinogen may prove a very useful tool for the diagnosis of lesions in the adnexa of the type endometriomas.

Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors.In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association.Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients50 years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients.Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients50 years, in whom differential diagnosis of ovarian tumors is particularly challenging.

OBJECTIVES: Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms. METHODS: Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate. RESULTS: More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p

Elevated plasma factor VIII (FVIII) is increasingly recognized as an independent risk factor for thrombotic diseases. Our aim was to evaluate the association of increased plasma FVIII with cerebral venous thrombosis (CVT). Forty eight patients with non-puerperal, aseptic CVT were recruited for the study along with 50 age- and gender-matched, healthy controls. Blood samples were collected 3 months after the thrombotic event in patients. Plasma FVIII and fibrinogen levels were measured by a functional clot-based assay. Mean plasma FVIII was significantly higher in patients when compared to controls (235.40 ± 94.5 vs.121.2 ± 28.3IU/dl, p0.001). Absence of significant elevation of fibrinogen suggested that the increase in FVIII was not due to an acute phase reaction. Elevated FVIII (170 IU/dl) was associated with18-fold increase in the risk for non-puerperal CVT (adjusted OR: 18.754, 95% CI 10.2-203.0, p0.001). Non-O blood groups were more prevalent in CVT patients. Mean FVIII levels were higher in subjects with non-O blood group as compared to those with O blood group (155.16 ± 46.05 vs. 129.09 ± 40.06 IU/dl, p0.001). Multivariate analysis with logistic regression showed that only elevated FVIII, and not blood group, was significantly associated with CVT. Our study demonstrates that elevated FVIII is an independent risk factor for non-puerperal CVT in an Indian population.

Objectives: In the present study, the authors have investigated whether rotational thromboelastometry (ROTEM) could predict thrombocytopenia and hypofibrinogenemia in cardiac surgery using the clot amplitude after 5 minutes (A5). Another parameter, PLTEM, in which the contribution of fibrinogen is eliminated by subtracting a fibrin-specific ROTEM test (FIBTEM) from an extrinsically-activated ROTEM test (EXTEM), was investigated. Furthermore, the turnaround time of ROTEM was compared to conventional laboratory tests.Design: Prospective cohort study.Setting: Single academic medical center.Participants: Ninety-seven patients undergoing cardiac surgery between July 2011 until August 2012.Interventions: The correlations between EXTEM/FIBTEM A5, A10, and maximal clot formation (MCF), EXTEM/PLTEM (A5/A10, and MCF) and platelet count, and FIBTEM (A5/A10, and MCF) and fibrinogen were evaluated using the Pearson's correlation coefficient and receiver-operating characteristic curves. Turnaround times of ROTEM tests and conventional laboratory tests were assessed in the central laboratory.Measurements and Main Results: EXTEM AS and FIBTEM A5 showed an excellent correlation with A10 (R:0.99/1.00) and MCF (R:0.97/0.99). The correlation between EXTEM AS and platelet count (R:0.74) was comparable with the correlation of A10 (R:0.73) and MCF (R:0.70) with platelet count. FIBTEM AS predicted fibrinogen levels (R:0.87) as well as A10 (R:0.86) and MCF (R:0.87). PLTEM AS (R:0.85) correlated better with platelet count than EXTEM A5 (R:0.74; p = 0.04) and showed significantly better area under the curve values than EXTEM for predicting thrombocytopenia (A5 p = 0.012, A10 p = 0.019). Turnaround time for ROTEM tests, 12 minutes, was comparable with emergency requests for platelet count, 13 minutes, and shorter than emergency requests for fibrinogen levels, 37 minutes.Conclusions: Implementation of PLTEM and FIBTEM AS in ROTEM-guided transfusion protocols may improve transfusion management.

We evaluate the clinical implication of hypercoagulability surrogates, D-dimer (fibrinolysis) and fibrinogen (thrombosis) levels, in PCI-treated patients. Baseline D-dimer and fibrinogen levels were measured (n=2,344). We stratified patients into four groups according to D-dimer and fibrinogen

Summary Objective There is a wealth of data routinely collected and stored by healthcare facilities, which are not consistently exploited for surveillance of healthcare associated infections (HCAI). Syndromic surveillance has not yet been widely applied to HCAI. This study aimed to create syndromic surveillance for surgical site infections (SSI) following coronary artery bypass graft (CABG) procedures. Methods A cohort of CABG patients from Imperial College Healthcare NHS Trust was investigated. Data from the local Patient Administration System, Laboratory Information Management System, radiology department, cardiac registry and Health Protection Agency SSI surveillance were linked. This data was explored for biological markers and proxies of infection, which were used to develop syndromic surveillance algorithms; sensitivity analysis was used to determine the best algorithms. Results 303 patients were included, with a SSI incidence of 6.6%. Wound culture requests, raised platelet and fibrinogen levels were all found to be good indicators of SSI. Two algorithms were generated, one to detect all SSI (sensitivity: 90%; specificity: 93.8%) and one to detect organ space infections specifically (sensitivity: 100%; specificity: 98.5%). Conclusion Data which is routinely collected and stored in healthcare facilities can be used for syndromic surveillance of SSI, allowing for an efficient surveillance system without the need for resource intensive data collection.

Evidence on the usefulness of fibrinogen for the risk stratification of patients with coronary artery disease remains inconclusive. The aims of this study were to investigate the association of fibrinogen with cardiovascular events and to assess whether this biomarker provides additional prognostic information on top of that provided by traditional cardiovascular risk factors. This study included 13,195 patients with angiography-proved coronary artery disease and fibrinogen measurements available. Receiver-operating characteristic curve analysis showed that the best fibrinogen cutoff for mortality prediction was 402.0 mg/dl. On the basis of this cutoff, patients were divided into 2 groups: the group with fibrinogen >402.0 mg/dl (n = 5,198) and the group with fibrinogen ≤402.0 mg/dl (n = 7,997). The primary outcome was 1-year mortality. All-cause deaths occurred in 393 patients with fibrinogen >402.0 mg/dl and in 246 patients with fibrinogen ≤402.0 mg/dl (Kaplan-Meier estimates of mortality 7.7% and 3.1%, log-rank test p

Cross-sectional and prospective studies have linked cardiovascular events and traditional risk factors (TRFs) with higher plasma fibrinogen levels. In a young cohort, we sought to determine longitudinal associations between changes in/development of TRFs and fibrinogen levels over 13 years.We included 2525 adults from the CARDIA study, aged 25-37 with fibrinogen and TRFs measured at year 7 (study baseline; 1992-1993); and year 20 (follow-up). Multiple linear regressions were used to compare mean changes in fibrinogen to TRFs.Mean fibrinogen increased by 71 mg/dL vs. 70 mg/dL (p = NS) in black vs. white men, and 78 mg/dL vs. 68 mg/dL (p 0.05) in black vs. white women, respectively over 13 years. After multivariable adjustments, fibrinogen generally rose with increasing BMI (p 0.001; all sex/race groups), LDL cholesterol, log triglycerides and diastolic blood pressure; and fell with increasing HDL cholesterol and physical activity. 13-year increase in fibrinogen for persons who quit smoking or became non-obese were comparable (p = NS) to that of never-smokers and never-obese persons.Among young black and white men and women with few baseline cardiovascular risk factors, fibrinogen tracked longitudinally with changes in TRFs over 13 years through middle age. There was a strong inverse longitudinal relationship between modifiable risk factors (weight loss/smoking cessation) and 13-year change in fibrinogen. Our study helps provide some insight into the role of fibrinogen as a disease marker in the associations between fibrinogen and CVD.

We report the case of a 7-month-old boy who developed hypofibrinogenemia (66.6 mg/dL; reference value, 170-405 mg/dL) during adrenocorticotropic hormone (ACTH) therapy for infantile spasms. Although the patient showed no clinical signs of a bleeding diathesis, we recommend that plasma fibrinogen levels should be monitored during ACTH therapy, which should be discontinued when fibrinogen levels fall below hemostatic levels (60.0mg/dL) or when bleeding tendencies are recognized.

Background Postpartum haemorrhage is an important cause of maternal morbidity and mortality. It is associated with haemostatic impairment which may exacerbate bleeding. Methods All deliveries over a 3-year period in a large UK unit were reviewed and cases of haemorrhage of 1500 mL or more identified. Laboratory records were reviewed and the lowest value for haemoglobin, platelet count and fibrinogen, and longest value for prothrombin time and activated partial thromboplastin time within 24 h of delivery were recorded. Results Of 18 501 deliveries there were 456 bleeds of 1500 mL or more (2.5%). Fibrinogen levels correlated best with blood loss (r −0.48 P < 0.01) and fell progressively as volume increased. Activated partial thromboplastin time was less sensitive (r 0.4 P < 0.01) to increasing blood loss. Prothrombin time did not correlate with blood loss (r 0.01). Activated partial thromboplastin time and prothrombin time remained within the normal range in most women despite large bleeds. Similar results were observed in women who received four or more units of red blood cells. Haemoglobin level was adequately maintained irrespective of blood loss. Based on UK national guidelines only 13 of 456 (3%) women should have received fresh frozen plasma, although it was given to 45; despite this, fibrinogen levels below the pregnancy-related normal range were observed in most cases. Conclusion Fibrinogen level was the parameter that best correlated with increasing volume of haemorrhage and was the most useful marker of developing haemostatic impairment. Guidelines for fresh frozen plasma use in major postpartum haemorrhage were rarely followed and should be reviewed.

Backround 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. Methods 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. Results 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. Conclusion 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.

This study retrospectively assesses whether significantly accelerating thrombolysis with ultrasound affects fibrinogen levels in the treatment of peripheral arterial occlusions.Between December 2005 and August 2007, 38 limbs in 38 patients (17 women; mean age, 60.5 +/- 19.7 years; age range, 17-94 years) were treated with ultrasound-accelerated thrombolysis for peripheral arterial occlusion (PAO) and deep vein thrombosis (DVT), with serum fibrinogen levels measured at baseline and every 24 hours. All occlusions were treated with alteplase (0.5-1.0 mg/h).Complete or partial lysis was achieved in 92.1% of patients. All patients received thrombolytic therapy with mean infusion time of 42.3 hours (range, 20-96 hours). As part of standard clinical practice, patients were not assessed angiographically overnight. Mean total alteplase dose was 40.6 mg (range, 18-96 mg). Across all patients, the fibrinogen level at the end of infusion decreased by an average of 18.5% from baseline, and no patient exhibited a fibrinogen level100 mg/dL during treatment. Fibrinogen depletion was more pronounced among patients with venous occlusions (26.4% from baseline) than those with arterial occlusions (15.8% from baseline). No major hemorrhagic complications occurred. One patient (2.6%) experienced a minor bleeding event at the access site, and use of thrombolytics was discontinued; and one patient with a chronic arterial occlusion and underlying coronary disease who did not respond to thrombolytic therapy, experienced an acute myocardial infarction. Of documented 30-day clinical outcomes in 20 patients, 80.0% remained patent at 30 days.Ultrasound-accelerated thrombolysis for the treatment of PAO and DVT is associated with a very low complication rate and nominal fibrinogen depletion.

Objective: To investigate the correlation of fibrinogen level and absorbance change in both PT and APTT clotting curves on BCSXP Analyzer. Methods:A serial of standard fibrinogen and 250 patient plasma samples with different qualities(normal, hemolysis,icterus, and lipemia) were run on BCSXP for assays PT, APTT and Fibrinogen. The absorbance change(DeltaA) from baseline to plateau in clotting curve was retrieved and analyzed on its correlation with the Fibrinogen result. Influence of plasma quality and PT/APTT result on this correlation was also studied respectively. Results:Both PT-DeltaA and APTT-DeltaA showed good linear regression with fibrinogen level in the sample, with Re close to 0.90 in both standard and patient samples. Hemolysis(H), itcterus(1) and lipemia(L) of the sample with valid clotting curves were found to have no significant difference in this correlation from normal(N) sample(R2: 0.83H, 0.92I 0.81L and 0.79N in PT; 0.89H, 0.95I, 0.91L and 0.89N in APTT) in either PT or APTT curve. PT or APTT result also has little impact on this correlation(0.71 in range 7 ～ 10 sec, 0.56 in10 ～ 20 sec, and 0.70 in 20 sec～; R2 in APTT: 0.88 in 20～30 sec,0.92 in 30～40 sec, and 0.95 in 40 sec～). Conclusion:The absorbance change in either PT or APTT clotting curve correlates well with the fibrinogen level in plasma, which is independent of plasma quality PT or APTT results. The absorbance change can be used as an alternative way to roughly estimate fibrinogen level in either PT or APTT clotting curve when the result of clauss-based fibrinogen measurement is not available.

Platelet thrombi are central to the development of most vascular ischemic events. There is marked interindividual variation in platelet responsiveness, with some subjects displaying platelet hyperreactivity. An increasing number of reports indicate that there are laboratory measures of platelet function that predict clinical thrombotic events. Some, but not all, measures of platelet function are reproducible. Platelet hyperreactivity can be assessed with multiple stimuli in multiple assays and is more likely to be present in women and in subjects who have elevated fibrinogen levels.

Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis.Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT.Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.

To explore the relationship between the composite index of the serum bilirubin and serum lipid variables, the serum fibrinogen(FIB) level and the severity of coronary heart disease. To investigate whether it is more significant for the composite index of the serum bilirubin and serum lipid variables

Higher fibrinogen level and on-thienopyridine platelet reactivity are associated with ischemic cardiac events after PCI, while relationships with bleeding after PCI are unclear. Subjects pretreated with thienopyridines undergoing elective or urgent (acute coronary syndrome [ACS]) PCI were enrolled

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared—15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates (P < .01), as well as in relative viscosity at both periods (P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation (P < .001) and fibrinogen level (P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery (P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

The formation of a fibrin clot is one of the key events in atherothrombotic vascular diseases, such as myocardial infarction, ischemic stroke and peripheral arterial disease. Fibrin is formed from a circulating precursor, fibrinogen, by the action of thrombin. Both genetic and environmental factors are important determinants of the circulating fibrinogen levels. Epidemiologic studies have demonstrated a role for this hemostatic protein in the prediction of cardiovascular disease. As an acute-phase reactant, fibrinogen is also a marker of inflammation. Likewise, recent studies from our group have shown that increased fibrinogen levels represent a marker of subclinical atherosclerosis, likely to be useful in the identification of asymptomatic subjects at risk for cardiovascular disease.

Erythrocyte aggregation is an indicator of cardiovascular risk, which is influenced by plasma fibrinogen concentration. Fibrinogen levels are elevated during cardiovascular diseases. Our main goals were to understand how fibrinogen-erythrocyte binding influences erythrocyte aggregation and how it constitutes a cardiovascular risk factor in essential arterial hypertension (EAH) and chronic heart failure (CHF). Fibrinogen-erythrocyte and erythrocyte-erythrocyte adhesion measurements were conducted by atomic force microscopy (AFM)-based force spectroscopy. Upon increasing fibrinogen concentration, there was an increase in the work and force necessary for cell-cell detachment, both for healthy donors and EAH patients. Nevertheless, higher values were obtained for the EAH patients at each fibrinogen concentration. Fibrinogen-erythrocyte (un)binding forces were higher in EAH and CHF patients, when compared with the control group, despite a lower binding frequency. Ischemic CHF patients showed increased binding forces compared to non-ischemic patients. Differences between CHF patients and healthy donors, in terms of erythrocyte elasticity (Young's modulus) and AFM tip penetration depth into the cells were also assessed. Erythrocytes from non-ischemic patients presented higher stiffness than those from the other two groups. Nevertheless, a significantly higher cell penetration depth at the same applied force was observed for ischemic heart failure patients. Erythrocyte deformability (assessed as elongation index) results show that heart failure patients presented higher erythrocyte deformability than the control group at lower shear stresses, and lower deformability at higher shear stresses. This indicates that patients’ erythrocytes are more deformable than those from healthy donors in blood vessels with larger internal diameters; however, in smaller-diameter vessels the opposite trend exists. Finally, a 12-month clinical follow-up shows that CHF patients with higher fibrinogen-erythrocyte binding forces, probed by AFM at the beginning of the assessment, had a significantly higher probability of being hospitalized due to cardiovascular complications on the subsequent year. Our results show that AFM can be a promising tool for clinical prognosis, pinpointing those patients with increased risk for cardiovascular diseases.Guedes et al. (2016) Nature Nanotechnology, 11:687-92.

To cite this article: Peyvandi F, Biguzzi E, Franchi F, Bucciarelli P, Acaia B, Zaina B, Musallam KM. Elevated prepartum fibrinogen levels are not associated with a reduced risk of postpartum hemorrhage. J Thromb Haemost 2012; 10: 1451–3.