Increased Fibrinogen Concentration Research Articles

Effects of fibrinogen concentration on fibrin glue and bone powder scaffolds in bone regeneration

Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 80mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6±3.6%, while the compressive strength increased 1.16±0.02Mpa, when compared with the values for the 10mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering.

Predictors of Obstetrical Complications: A Prospective Cohort Study

Background: The objective was to identify predictors of obstetrical complications. Methods: A prospective cohort study, a state-run obstetrical hospital, Omsk, Russia. Out of a total 2,497 pregnant women with a gestation age of less than 12 weeks, 2,356 women with singlet pregnancies were selected. Data at gestation outcome were available for 2,177 women. Medical and social factors were evaluated and blood coagulation screening was performed in women in the first trimester. Ordered logistic regression was used to assess risks of obstetrical complications. The following obstetrical complications were evaluated after 28 weeks of gestation: preeclampsia, abruptio placentae, preterm labor, intrauterine growth restrictio n a nd intrauterine hypoxia. Results: A prognostic model comprised of 21 predictors (P < 0.001) with strong association (0.82) between the studied parameters and the obstetrical complications was obtained. Probability of obstetrical complications (91.1%) was associated with the following parameters in women: age, education, parity, medical history, heredity (family history ) and blood coagulation profile. Increased fibrinogen concentrations and reduced thrombin clotting time in the first trimester w ere associated with severe obstetrical complications late in pregnancy. Conclusions: Women with late obstetrical complications were found to have increased blood viscosity and an increase in coagulation potential early in pregnancy. The prognostic model obtained may have great significance and requires further validation. J Clin Gynecol Obstet. 2014;3(1):14-21 doi: http://dx.doi.org/10.14740/jcgo202w

Prevalence, predictors and outcome of hypofibrinogenaemia in trauma: a multicentre observational study

IntroductionExsanguination due to trauma-induced coagulopathy is a continuing challenge in emergency trauma care. Fibrinogen is a crucial factor for haemostatic competence, and may be the factor that reaches critically low levels first. Early fibrinogen substitution is advocated by a number of authors. Little evidence exists regarding the indications for fibrinogen supplementation in the acute phase. This study aims to estimate the prevalence of hypofibrinogenaemia in a multi-center trauma population, and to explore how initial fibrinogen concentration relates to outcome. Also, factors contributing to low fibrinogen levels are identified.MethodsPatients arriving in hospital less than 180 minutes post-injury requiring full trauma team activation in four different centers were included in the study. Time from injury, patient demographics, injury severity scores (ISS) and 28 days outcome status were recorded. Initial blood samples for coagulation and blood gas were analyzed. Generalized additive regression, piecewise linear regression, and multiple linear regression models were used for data analyses.ResultsOut of 1,133 patients we identified a fibrinogen concentration ≤1.5g/L in 8.2%, and <2 g/L in 19.2%. A non-linear relationship between fibrinogen concentration and mortality was detected in the generalized additive and piecewise linear regression models. In the piecewise linear regression model we identified a breakpoint for optimal fibrinogen concentration at 2.29 g/L (95% confidence interval (CI): 1.93 to 2.64). Below this value the odds of death by 28 days was reduced by a factor of 0.08 (95% CI: 0.03 to 0.20) for every unit increase in fibrinogen concentration. Low age, male gender, lengthened time from injury, low base excess and high ISS were unique contributors to low fibrinogen concentrations on arrival.ConclusionsHypofibrinogenaemia is common in trauma and strongly associated with poor outcome. Below an estimated critical fibrinogen concentration value of 2.29 g/L a dramatic increase in mortality was detected. This finding indicates that the negative impact of low fibrinogen concentrations may have been previously underestimated. A number of clinically identifiable factors are associated with hypofibrinogenaemia. They should be considered in the management of massively bleeding patients. Interventional trials with fibrinogen substitution in high-risk patients need to be undertaken.

C-Reactive Protein and Fibrinogen as Indicators of Systemic Inflammatory Response in Patients Undergoing VATS and Conventional Pulmonary Lobectomy

Abstract Introduction. There is still ongoing discussion about superiority of video-assisted thoracoscopic surgery or VATS approach for performing lobectomy over conventional pulmonary lobectomy performed by open thoracotomy for the treatment of non-small cell lung cancer at an early stage. Aim of the study. This encouraged us to conduct a prospective study for evaluation and comparison of the systemic inflammatory response by using these two approaches. Materials and methods. We have conducted a prospective study for evaluation of C-reactive protein and Fibrinogen as indicators of systemic inflammatory response during early postoperative course. Surgery was prospectively randomised in two groups: 15 patients underwent VATS lobectomy and 15 patients underwent conventional open lobectomy. Blood samples were taken preoperatively, 24 and 72 hours after operation, on the day of drain removal, and 1 and 9 days after the drain removal. Results. Surgery caused systemic inflammatory response in both groups. The increase in CRP was notably higher in OL group in all measurements except preoperative (p&lt;0,05). The increase in Fibrinogen concentrations was also higher in OL group but statistical significance (p&lt;0,05) was reached only in day of drain removal. Conclusions. VATS approach caused reduced systemic inflammatory response compared with conventional open thoracotomy approach and was also associated with lesser postoperative pain as duration of chest drains and total amount of drained effusion is significantly smaller.

Rheological and Turbidity Study of Fibrin Hydrogels

SummaryFibrin hydrogels prepared from different fibrinogen concentrations (12.5, 25 and 50 mg/mL) were studied through oscillatory rheology (gelation kinetics, stress amplitude tests and frequency sweeps), static experiments (creep and recovery tests) and turbidity (gelation kinetics). The experimental parameters obtained from these measurements (including gel point, characteristic times for different kinetic phases, loss and storage moduli), were used to gain some insight on the processes concurring to form the network structure of fibrin hydrogels. Here, we show (turbidity measures) that lateral fibre aggregation appears to be significantly depressed with increasing fibrinogen concentration. Among other important findings, a caveat in using absolute data of mechanical properties from gelation kinetics: we have shown that at low fibrinogen concentration, the actual modulus values are significantly affected by the application of shear stress during gelation.

Blood rheology and aging.

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concentration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.

Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

AbstractFibrinogen γ′ is known to influence fibrin clot structure in purified experimental models, but little is known regarding its influence on clot structure in plasma. Furthermore, the environmental and biological factors that affect its concentration are poorly described. We analyzed fibrinogen γ′, total fibrinogen concentration, and fibrin clot structure in 2010 apparently healthy black South Africans and related them to traditional cardiovascular disease (CVD) risk factors. Fibrinogen γ′ generally increased with increasing fibrinogen concentration, but a decreased γ′/total fibrinogen ratio was found at the highest total fibrinogen concentrations. Clot maximum absorbance increased with total fibrinogen and fibrinogen γ′, but decreased with γ'/total fibrinogen ratio. Clot lysis time showed a stronger relationship with fibrinogen γ′ than with total fibrinogen, whereby increased fibrinogen γ′ delayed clot lysis. CVD risk factors (excluding fibrinogen) explained 20% and 3%, respectively, of the variance in fibrinogen γ′ and the γ′/total fibrinogen ratio, with C-reactive protein making the biggest contribution. More than 50% of the variance in fibrinogen γ′ and γ′/total fibrinogen ratio is explained by factors other than total fibrinogen or other traditional CVD risk factors. Our data show that fibrinogen γ′ modulates plasma clot structure and fibrinolysis and is also influenced by factors other than fibrinogen.

Disaggregating shear stress: The roles of cell deformability and fibrinogen concentration

Red blood cell (RBC) aggregation is greatly affected by cell deformability and reduced deformability and increased RBC aggregation are frequently observed in hypertension, diabetes mellitus, and sepsis, thus measurement of both these parameters is essential. In this study, we investigated the effects of cell deformability and fibrinogen concentration on disaggregating shear stress (DSS). The DSS was measured with varying cell deformability and geometry. The deformability of cells was gradually decreased with increasing concentration of glutaraldehyde (0.001~0.005%) or heat treatment at 49.0°C for increasing time intervals (0~7 min), which resulted in a progressive increase in the DSS. However, RBC rigidification by either glutaraldehyde or heat treatment did not cause the same effect on RBC aggregation as deformability did. The effect of cell deformability on DSS was significantly increased with an increase in fibrinogen concentration (2~6 g/L). These results imply that reduced cell deformability and increased fibrinogen levels play a synergistic role in increasing DSS, which could be used as a novel independent hemorheological index to characterize microcirculatory diseases, such as diabetic complications with high sensitivity.

Characterization of Flowing Blood Optical Property Under Various Fibrinogen Levels Using Optical Coherence Tomography

The feasibility of characterization of human blood fibrinogen levels using optical coherence tomography (OCT) was investigated. Three groups of blood samples were reconstituted of red blood cells: 1) phosphate-buffered saline; 2) plasma with its intrinsic fibrinogen removed and commercial fibrinogen added; and 3) native plasma with various fibrinogen levels (0-12 g/L). OCT signal slope (OCTSS) of blood was extracted from OCT depth-reflectivity profiles. Effects of hematocrit (HCT) and blood flow on OCTSS of the blood under various fibrinogen concentrations were also studied. The results of blood flowing at 5 mm/s showed that OCTSS of all the three groups at HCT of 40% decreases with the increasing fibrinogen concentration up to a certain level, i. e., >8, 6, and 4 g/L for groups 1, 2, and 3, respectively. The blood of group 2 at HCTs of 30%, 40%, and 50% had a rapid decrease in OCTSS in the range of fibrinogen concentration of 0-2, 0-6, and 0-10 g/L, respectively. OCTSS value of blood flowing at 2.5 mm/s was lower than that at 5 mm/s at each fibrinogen concentration. In conclusion, OCTSS has a strong correlation with plasma fibrinogen concentration, and has the potential to identify the abnormal level of human blood fibrinogen.

Daily Profiles of Fibrinogen Metabolism for 5 Days Following Hemorrhage and Lactated Ringer’s Resuscitation in Pigs

This study's objective was to investigate the daily dynamics of fibrinogen metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. Then, a primed constant infusion of stable isotopes was performed in both groups daily for 5 days to measure changes in fibrinogen metabolism, together with changes in hemodynamics and coagulation function. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate. Fluid resuscitation corrected these changes. Compared with baseline day 1, fibrinogen levels in H were decreased to 76% ± 6% by hemorrhage and resuscitation on day 1, increased to 217% ± 16% on day 2, and remained elevated afterward; clot strength in H was decreased by hemorrhage on day 1 and returned to baseline values on day 2 and afterward. Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in fibrinogen concentration and clot strength, followed by an increase in fibrinogen concentration and recovery of clot strength. The increase in fibrinogen appeared primarily due to a sustained increase in fibrinogen synthesis.

The prognostic value of plasma fibrinogen concentrations of patients with ST-elevation myocardial infarction and treated by primary percutaneous coronary intervention: A cautionary message

Background. Fibrinogen elevation is associated with a worse prognosis in patients with acute coronary syndrome (ACS). The aim of the present study was to assess the prognostic value of increased fibrinogen concentrations in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods. A total of 428 STEMI patients treated with primary PCI were retrospectively selected (median age: 62 years; 82.5% males) from a continuous case series of 832 ACS patients. Plasma fibrinogen concentrations were measured before PCI and after 24, 48, and 72 hours. In the 4-year follow-up, one major adverse cardiovascular event (MACE) occurred in 111 patients (40%): 17 re-STEMI (7%), 64 re-PCI (22%), 22 cardiac deaths (7%), and eight non ST-elevated acute coronary syndromes (NSTEACS, 4%). Results. According to the reference change value, fibrinogen concentrations increased in 25% of patients at 24 h, 64% at 48 h and 19% at 72 h. Only fibrinogen concentrations at 48 h showed a mild association with overall MACEs (p = 0.036): the risk increased, starting from a concentration of 4 g/L. However a further multivariate model did not confirm any prognostic value. No association with specific MACEs emerged. Conclusions. In contrast to NSTEACS patients, fibrinogen concentrations increased slightly in STEMI patients after primary PCI, however, they were not as prognostic as for MACEs.

Effect of chronic hyperglycaemia on the parameters of protein, lipid metabolism and platelet-coagulation haemostasis in acromegaly

The aim of the research. Assessing the impact of chronic hyperglycemia on the parameters of the protein, lipid metabolism and platelet-coagulation haemostasis in patients with active phase of acromegaly. Materials and methods: The research included 58 patients with the active phase of acromegaly (36 women and 28 men), median age 50 (43, 57) years, disease duration 9.0 (5.0, 15.0) years, 26 of whom had verified diabetes mellitus. Results: Biochemical parameters and parameters of haemostasis in patients with active phase of acromegaly with normoglycemia differed from the control group by higher levels of total cholesterol, high-density lipoproteins, an increase in the average volume of platelet aggregation and enhancement of their function. The presence of diabetes mellitus was accompanied by the increase in concentration of total cholesterol, triglycerides, decrease in high-density lipoproteins, and increase in fibrinogen concentration, soluble fibrin-monomeasured complexes, as well as reduction of disaggregation properties of platelets and enhancement of ejection reactions. Conclusion: The presence of diabetes mellitus with acromegaly can be regarded as a significant risk factor for atherogenic dyslipidemia, hyperfibrinogenemia and platelet disfunction.

Neurite Outgrowth in Fibrin Gels Is Regulated by Substrate Stiffness

Fibrin is a promising matrix for use in promoting nerve repair given its natural occurrence in peripheral nerve injuries, and the biophysical properties of this matrix can be regulated to modulate tissue regeneration. In this study, we examined the effect of physical and mechanical properties of fibrin gels on dorsal root ganglia (DRG) neurite extension. Increases in fibrinogen concentration increased the number of fibrin strands, resulting in decreased pore size and increased stiffness. Neurite extension was reduced when DRG explants were cultured within fibrin gels of increasing fibrinogen concentrations (from 9.5 to 141 mg/mL). The addition of NaCl also increased the number of fibrin strands, reducing fiber diameter and porosity, while increasing mechanical strength, and reductions in neurite extension correlated with increases in NaCl content. We determined that neurite extension within fibrin gels is dependent on fibrinolysis and is mediated by the secretion of serine proteases and matrix metalloproteinases by entrapped DRGs, as confirmed by culturing cells in the presence of inhibitors against these enzymes and real-time-polymerase chain reaction. Taken together, the results of this study provide new insight into the effect of fibrin gel biophysical properties on neurite extension and suggest new opportunities to improve the efficacy of these materials when used as nerve guidance conduits.

In vitro adipogenesis of adipose-derived stem cells in 3D fibrin matrix of low component concentration

This study evaluated the suitability of adipose-derived stem cells (ASCs) combined with fibrin matrix of variable composition for adipose tissue-equivalent formation in vitro. Therefore, undifferentiated ASCs were embedded in fibrin clots composed of 2 IU/ml thrombin and fibrinogen of varying concentrations (6.25, 12.5 and 25 mg/ml) and kept under control or adipogenic conditions. Fibrin-cell composites were evaluated by scanning electron microscopy, live/dead staining, lactate-dehydrogenase (LDH) assay, quantitative PCR for the adipogenic markers fatty acid binding protein 4 (FABP4), peroxisome proliferative activated receptor-γ (PPARγ) and leptin, leptin ELISA and oil red O staining. Cells were found homogeneously distributed throughout the clot. Their number increased to day 7 (up to 3.62-fold median) and decreased thereafter until day 28. The proliferation was unaffected by fibrinogen concentration in the control. Adipogenic conditions generally yielded higher cell numbers, which were in addition increasing with increasing fibrinogen concentrations. FABP4, PPARγ and leptin mRNA expression was strongly upregulated by adipogenic medium, which was confirmed by the levels of leptin secretion and lipid vesicles formation demonstrated by oil red O staining. When embedded in 25 mg/ml fibrinogen clots, ASCs showed the highest expression levels of FABP4 (up to 629.0-fold), PPARγ (up to 1.6-fold) and leptin (up to 57.9-fold), corroborated by significantly elevated leptin secretion (median 33.29 ng/ml) on day 14. Constructs composed of fibrin matrix of low component concentrations-allowing homogeneous cell distribution-with ASCs should represent a suitable strategy for adipose tissue formation in vivo.

Impact of Acute Normovolemic Hemodilution with Autoplasma Transfusion on Hemostatic Parameters during Abdominal Delivery

Objective: to evaluate the impact of acute normovolemic hemodilution (ANH) with autoplasma transfusion on hemostatic parameters during cesarean section. Subjects and methods. The study covered 119 patients in whom ANH was used during cesarean section. Group 1 included 62 women undergoing ANH with autoplasma transfusion; Group 2 (control) comprised 57 pregnant women receiving ANH only. Examination of the hemostatic system involved studies of the plasma link, thromboelastogram readings, vascular platelet hemostasis and evaluation of intravascular thrombogenesis. Results. Transfusion of stored autoplasma as a hemostatic component during ANH favored the development of moderate hypercoagulation due to a significant increase in fibrinogen concentrations by 8%, r+k shortening by 11%, and a rise in the thrombodynamic potential index by 12%. A statistically significant difference has been found in the results between the groups at a stage of surgical hemostasis, which proves the best hemostat-ic effect of ANH used with autoplasma transfusion. Conclusion. The study has demonstrated that the combined use of ANH and autoplasma transfusion contributes to the stabilization of the blood coagulation potential during cesarean section and extends the feasibilities of ANH when the volume of intraoperative blood loss is as high as 25% of the circulating blood volume. Key words: cesarean section, acute normovolemic hemodilution, autoplasma transfusion, coagulation potential.

Hemostatic abnormalities in dogs with carcinoma: A thromboelastographic characterization of hypercoagulability

Hemostatic abnormalities were investigated in 32 dogs with carcinoma and 19 age-matched healthy dogs. Thromboelastography, hemostasis profile (i.e. prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), platelet count (PLT), thrombin-antithrombin complexes (TAT), and plasminogen activator inhibitor-1 (PAI-1) activity were evaluated. Dogs with carcinomas had faster thrombus generation (TEG(TG), a mathematic value obtained from the first derivate of the thromboelastographic tracing; 834.8±91.1 vs. 707.8±75.8mm/min; mean±SD), increased fibrinogen concentration (276 vs. 151mg/dL), and PLT (425 vs. 324U×10(9)/L), but had decreased PAI-1 activity (15.7 vs. 26.2IU/mL).The most common hemostatic abnormalities found in carcinoma dogs were hypercoagulability (TEG(TG)>mean+2 SD of healthy dogs) and thrombocytosis (PLT>424×10(9)U/L) in 46% of cases, and hyperfibrinogenemia (fibrinogen >384mg/dL) in 32% of cases. Disseminated intravascular coagulation was uncommon and the extent of disease was not correlated with hypercoagulability. TEG(TG) showed good correlation with fibrinogen (r=0.80) and hyperfibrinogenemia seems to be a main factor of the hypercoagulable state in carcinoma dogs. In conclusion, TEG(TG) is a valid parameter to diagnose hypercoagulability.

Fibrinogen concentration and its role in CVD risk in black South Africans – effect of urbanisation

The aim of this study was to investigate correlates of fibrinogen concentration in black South Africans, as well as its association with cardiovascular disease (CVD) risk and whether urbanisation influences this association. A total of 1,006 rural and 1,004 urban black South Africans from the PURE study were cross-sectionally analysed. The association of fibrinogen with CVD risk was determined by investigating the association of fibrinogen with other CVD risk markers as well as with predicted CVD risk using the Reynolds Risk score. The rural group had a significantly higher fibrinogen concentration than the urban group, despite higher levels of risk factors and increased predicted CVD risk in the urban group. Increased levels of CVD risk factors were, however, still associated with increased fibrinogen concentration. Fibrinogen correlated significantly, but weakly, with overall predicted CVD risk. This correlation was stronger in the urban than in the rural group. Multiple regression analysis showed that a smaller percentage of the variance in fibrinogen is explained by the traditional CVD risk factors in the rural than in the urban group. In conclusion, fibrinogen is weakly associated with CVD risk (predicted overall risk as well with individual risk factors) in black South Africans, and is related to the degree of urbanisation. Increased fibrinogen concentration, in black South Africans, especially in rural areas, is largely unexplained, and likely not strongly correlated with traditional CVD-related lifestyle and pathophysiological processes. This does, however, not exclude the possibility that once increased, the fibrinogen concentration contributes to future development of CVD.

Effects of fibrinogen concentrate administration during severe hemorrhage

Fibrinogen concentrate has been shown to improve coagulation in dilutional coagulopathy in experimental studies, but clinical experience is still scarce. The aim of this study was to evaluate laboratory data and the clinical outcome of fibrinogen administration in patients suffering from severe hemorrhage. A retrospective study over a 3-year observation period of consecutive patients who received a single dose of fibrinogen concentrate but not recombinant factor VIIa as part of their treatment of severe hemorrhage, defined as >6 U of packed red blood cells (PRBCs). Thirty-seven patients were included, most of them suffering from severe hemorrhage following open heart surgery (68%). After a median fibrinogen dose of 2 g (range 1-6 g), an absolute increase in the plasma fibrinogen concentration of 0.6 g/l was observed (P<0.001). The activated partial thromboplastin time (APTT) decreased significantly (P<0.001), from 52 to 43 s and the prothrombin time (PT) decreased from 20 to 17 s, respectively. The transfusion requirement for PRBCs decreased from 6 to 3 U (P<0.01) in the 24 h after fibrinogen administration, but fresh-frozen plasma and platelet concentrate transfusions did not change significantly. Eight patients (22%) died in intensive care unit and the pre-operative fibrinogen concentration was not significantly different in these patients. Administration of fibrinogen for severe hemorrhage was associated with an increased fibrinogen concentration and a significant decrease in APTT, PT and the requirement for PRBCs.

Prognostic significance of preoperative plasma fibrinogen in endometrial cancer

Objective To investigate the prognostic significance of preoperative plasma fibrinogen concentration, with particular focus on tumor dissemination and nodal involvement, in a substantial cohort of patients with endometrial cancer. Methods The study population comprised 336 women with endometrial cancer who underwent surgical staging at two tertiary institutions, from 2000 to 2009. Pretreatment plasma samples from the study cohort were assayed for fibrinogen by the Clauss assay. Information on demographics, laboratory testing, histopathology and follow-up was gathered from databases of prospectively collected data. Factors associated with survival were identified in a Cox proportional hazards model. Univariate and multivariate analyses were used to evaluate predictors of extrauterine disease and nodal metastasis. Results One-hundred-thirty-seven (40.8%) patients exhibited preoperative hyperfibrinogenemia. Univariate analysis demonstrated that histological type, tumor grade, depth of myometrial invasion, surgical stage, patient age, and hyperfibrinogenemia affect disease-free (DFS) and overall survival rates significantly. When these variables were entered simultaneously into a Cox regression model, raised preoperative levels of plasma fibrinogen retained significance as poor prognosticator of DFS (HR 2.0, 95%CI 1.1–3.6) and overall survival (HR 2.7, 95%CI 1.3–5.5). Preoperative hyperfibrinogenemia was an independent determinant of extrauterine disease (OR 2.7, 95%CI 1.3–5.6). In the subcohort of women with endometrioid histology, increased fibrinogen concentration at presentation was predictive of pelvic nodal involvement (OR 3.6, 95%CI 1.1–11.7). Conclusion Plasma fibrinogen level may be of value in the prediction of outcome, improve the stratification of endometrial cancer patient, at diagnosis, based on their risk of recurrence, and possibly alter their treatment accordingly.

Fibrinogen Assays for Cardiovascular Risk Assessment

In this issue of Clinical Chemistry , Lovely and colleagues(1) report an evaluation of a new plasma fibrinogen assay for the study of its associations with cardiovascular disease. So, what is the current status of plasma fibrinogen in cardiovascular risk assessment, and how might this new assay advance our knowledge and practice? Fibrinogen, the precursor of fibrin, was the first blood coagulation factor to be described—in 1836 by Buchanan at the University of Glasgow(2). By 1995, many studies had established that the plasma fibrinogen concentration was associated not only with coronary heart disease but also with cerebrovascular and peripheral vascular diseases(2). These associations have led to evaluation of fibrinogen as a possible causal factor in cardiovascular disease, as a therapeutic target, and as a risk predictor in both healthy persons and those with established cardiovascular diseases. The association of fibrinogen with risks of cardiovascular disease and mortality in healthy individuals has been reliably established through international collaborative individual-person metaanalyses, the Fibrinogen Studies Collaboration (http://www.phpc.cam.ac.uk/MEU/FSC/), and its successor, the Emerging Risk Factors Collaboration (http://www.phpc.cam.ac.uk/MEU/ERFC/)(3)(4). The strength of fibrinogen’s associations with coronary heart disease and stroke is similar to those of classic risk factors, such as blood pressure and serum cholesterol, and to the circulating concentration of C-reactive protein (CRP), which, like fibrinogen, is a marker of the inflammatory response, including low-grade inflammation in healthy persons(4). Is fibrinogen a causal risk factor in cardiovascular disease? Increasing fibrinogen concentrations might promote risk …