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PubMed1999

A prospective study of fibrinogen and risk of myocardial infarction in the Physicians' Health Study.

OBJECTIVES: We examined the association of baseline plasma fibrinogen with future risk of myocardial infarction (MI) in the Physicians' Health Study. BACKGROUND: Elevated plasma fibrinogen increases and low dose aspirin decreases risk of MI. However, prospective data are limited about their interrelationships. METHODS: Blood samples were prospectively collected at baseline from 14,916 men in the Physicians' Health Study, aged 40 to 84 years, who were randomly assigned to take aspirin (325 mg every other day) or placebo for 5 years. We measured baseline plasma fibrinogen among 199 incident cases of MI and 199 age- and smoking-matched control subjects free of cardiovascular disease at the time of the case's diagnosis. RESULTS: Cases had significantly higher baseline fibrinogen levels (geometric mean: 262 mg/dl) than did control subjects (245 mg/dl, p = 0.02). Those with high fibrinogen levels (> or =343 mg/dl, the 90th percentile distribution of the control subjects) had a twofold increase in MI risk (age- and smoking-adjusted relative risk = 2.09, 95% confidence interval = 1.15 to 3.78) compared with those with fibrinogen below 343 mg/dl. Adjustment for lipids and other coronary risk factors as well as randomized aspirin assignment did not materially change the result. Furthermore, we observed no interaction between fibrinogen level and aspirin treatment. CONCLUSIONS: Among these apparently healthy U.S. male physicians, fibrinogen is associated with increased risk of future MI independent of other coronary risk factors, atherogenic factors such as lipids and antithrombotics such as aspirin.

Adult↗
PubMed2003

Fibrinogen predicts mortality in high risk patients with peripheral artery disease.

OBJECTIVE: Fibrinogen plays a key role in the pathogenesis of atherosclerosis and complications of atherothrombotic disease. We investigated the prognostic impact of fibrinogen levels on mortality of high risk patients with peripheral artery disease (PAD). METHODS: We studied 486 patients with PAD and several cardiovascular comorbidities. Atherosclerotic risk factors and fibrinogen levels were determined at initial presentation and patients were followed for median 7 years (IQR 6-10) for all-cause and cardiovascular mortality. Multivariate Cox regression analysis was applied to assess the predictive value of fibrinogen levels (in quartiles) on patients' outcome. RESULTS: Cumulative survival rates at 1, 3, 5 and 10 years were 96, 91, 83 and 67%, respectively. Overall, 138 patients (28%) died, 70% of these patients died of cardiovascular complications (n=96). Patients with fibrinogen levels 10.2-12.2 micromol/l (third quartile) and patients with fibrinogen levels above 12.2 micromol/l (fourth quartile) had a significantly increased adjusted risk for all-cause mortality (hazard ratios [HR] 1.87 and 1.90, p=0.025 and p=0.020, respectively) compared to patients in the lowest quartile (fibrinogen below 8.6 micromol/l). A consistent effect was observed for cardiovascular causes of death. Diabetes mellitus and critical limb ischemia were the only other independent predictor variables (HR 2.08, p<0.001 and 1.88, p=0.001, respectively). CONCLUSION: Elevated fibrinogen levels in high risk patients with PAD indicate an increased risk for poor outcome, particularly for fatal cardiovascular complications.

Aged↗
PubMedDate not supplied

Direct observation of fibrinogen-heparinoid complexes formation using surface plasmon resonance.

We analyzed the binding of heparinoid or heparin with fibrinogen by real-time measurement using surface plasmon resonance technology. Poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA) sulfate] and dextran sulfate were used as heparinoids. The binding ability of each sulfated polymer was estimated by having each polymer-containing buffer interact with the sensor chip surfaces that had immobilized fibrinogen. Dextran sulfate and poly(GEMA) sulfate showed high affinity to the fibrinogen in this experiment, while the heparin did not. All of the dextran sulfates were desorbed from its surface, while about 30% of the poly(GEMA) sulfate remained on the immobilized fibrinogen upon the addition of NaCl to the buffer which was done in order to analyze the desorption of poly(GEMA) sulfate or dextran sulfate from the surface of the fibrinogen. These data show that the type of binding between fibrinogen-poly(GEMA) sulfate was different from that of dextran sulfate, indicating that the interaction between fibrinogen and poly(GEMA) sulfate was caused not only by an electrostatic but also by a hydrophobic force. These results suggest that the interaction mechanism of heparinoids with fibrinogen was different from that of heparin.

Biopolymers↗
PubMed2000

Interactions of human fibrinogens with factor XIII: roles of calcium and the gamma' peptide.

Plasma factor XIII is the zymogen of the transglutaminase factor XIIIa. This enzyme catalyzes the formation of isopeptide cross-links between fibrin molecules in nascent blood clots that greatly increase the mechanical stability of clots and their resistance to thrombolytic enzymes. We have characterized the solution interactions of factor XIII with two variants of fibrinogen, the soluble precursor of fibrin. Both the predominant fibrinogen gamma(A)/gamma(A) and the major variant gamma(A)/gamma' form complexes with a 2 fibrinogen:1 factor XIII ratio. The absence of detectable concentrations of 1:1 complexes in equilibrium mixtures containing free factor XIII and 2:1 complexes suggests that this interaction is cooperative. Factor XIII binds fibrinogen gamma(A)/gamma' approximately 20-fold more tightly than fibrinogen gamma(A)/gamma(A), and the interaction with fibrinogen gamma(A)/gamma' (but not fibrinogen gamma(A)/gamma(A)) is accompanied by a significant release of Ca(2+). Taken together, these results suggest that the strikingly anionic gamma' C-terminal sequence contains features that are important for factor XIII binding. Consistent with this notion, a synthetic 20-residue polypeptide containing the gamma' sequence was found to associate with factor XIII in a 2:1 molar ratio and act as an efficient competitor for fibrinogen gamma(A)/gamma' binding.

Binding, Competitive↗
PubMed1992

Modulation of thrombin-fibrinogen interaction by specific ion effects.

Steady-state measurements of synthetic substrate hydrolysis by human alpha-thrombin in the presence of human fibrinogen, under experimental conditions where light scattering due to the formation of fibrin aggregates is negligible, have allowed for a quantitative evaluation of Km for fibrinogen. Measurements of Km for fibrinogen carried out at pH 7.5 and 37 degrees C as a function of NaCl, NaBr, KCl, and KBr concentration, from 50 to 500 mM, show that the derivative d ln Km/d ln a +/-, where a +/- is the mean ion activity, is constant over the entire range of salt concentrations and is strictly dependent on the particular salt present in solution. The values of d ln Km/d ln a +/- are found to be equal to 0.75 +/- 0.03 (NaCl), 0.90 +/- 0.01 (NaBr), 0.62 +/- 0.07 (KCl), and 0.60 +/- 0.03 (KBr). Measurements of Km for two synthetic amide substrates, under identical solution conditions, reveal practically no change in Km with salt concentration, while they show a significant decrease in kcat when Na+ salts are replaced by K+ salts. The drastic difference in the salt dependence of Km between fibrinogen and the synthetic amide substrate points out that a significant role may be played by the fibrinogen recognition site in the energetics of thrombin-fibrinogen interaction. The sensitivity of Km for fibrinogen to different salts unequivocally demonstrates that specific ion effects, rather than nonspecific ionic strength effects, modulate thrombin-fibrinogen interaction under experimental conditions of physiological relevance. Analysis of ion effects on clotting curves obtained at pH 7.5 and 37 degrees C also shows a drastic differential effect of cations and anions.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗
PubMed1984

Glycosylated A alpha chains in chicken fibrinogen.

Fibrinogen immunoprecipitated from cultured chick embryo hepatocytes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and compared with fibrinogen from chicken plasma. The character and relatedness of the constituent polypeptide bands were established on the basis of enzymatic treatment, peptide analysis, metabolic labeling with [14C]glucosamine, and inhibition of glycosylation with tunicamycin. Hepatocyte-derived fibrinogen resolved into five polypeptides that, in order of decreasing apparent molecular weight, were identified as glycosylated A alpha, non-glycosylated A alpha, B beta, gamma', and gamma. Fibrinogen immunoprecipitated directly from chicken plasma yielded an identical profile except for an additional smaller A alpha chain. This small A alpha chain appears to be the product of partial proteolysis in the circulation and was the only A alpha band found in purified plasma fibrinogen (fraction I-2). The observation of glycosylated A alpha chains is novel. The gamma/gamma' chain heterogeneity appears to be due to an amino acid extension similar to that observed in mammalian fibrinogens. Fibrinogen from cells exposed to fetal bovine serum, a potent stimulator of fibrinogen production, was enriched in glycosylated A alpha chains, which constituted approximately one-third of the A alpha chain population. Serum did not affect the gamma/gamma' chain distribution.

Animals↗
PubMed1988

C1q component of complement binds to fibrinogen and fibrin.

The interaction of complement component C1q with fibrinogen and fibrin was studied by using a solid-phase direct binding assay. Scatchard analysis of radioiodinated fibrinogen binding to C1q indicated at least two high-affinity binding constants (Kd) calculated as 8.5 and 120 nM. In contrast, binding of radioiodinated fibrin to C1q showed only a single class of binding sites with a calculated Kd of 600 nM. Fibrinogen-C1q binding was shown to decrease as a function of increasing salt concentrations, indicating either the presence of charged amino acids in the binding sites or an ionic strength induced conformational dependency of the binding. In direct binding studies using isolated fragments of C1q, both the collagen-like domain of C1q and the globular domains of C1q were shown to bind fibrinogen, indicating at least one binding site for fibrinogen is located in each of the major domains of C1q. Addition of the thrombin-generated peptides of fibrinogen, fibrinopeptides A and B, enhanced C1q-fibrinogen binding, again indicating a complex binding interaction. These results indicate that C1q and fibrinogen are capable of high-affinity interactions that may serve to sequester these complexes in areas of tumors, immune complex deposition, or wounds.

Binding Sites↗
PubMed2005

Interactions of thrombin with fibrinogen adsorbed on methyl-, hydroxyl-, amine-, and carboxyl-terminated self-assembled monolayers.

We have examined the initial phase of fibrin formation, thrombin-catalyzed fibrinopeptide cleavage, from adsorbed fibrinogen using surface plasmon resonance and liquid chromatography-mass spectrometry. Fibrinogen adsorption impaired thrombin-fibrinogen interactions compared to the interactions of thrombin with fibrinogen in solution. The properties of the underlying substrate significantly affected the extent and kinetics of fibrinopeptide cleavage, and the conversion of adsorbed fibrinogen to fibrin. Fibrinogen adsorbed on negatively charged surfaces (carboxyl-terminated self-assembled monolayers) released a smaller amount of fibrinopeptides, at a reduced rate relative to those of hydrophobic, hydrophilic, and positively charged surfaces (methyl-, hydroxyl-, and amine-terminated self-assembled monolayers, respectively). Additionally, the conversion of adsorbed fibrinogen to fibrin was comparatively inefficient at the negatively charged surface. These data correlated well with trends previously reported for fibrin proliferation as a function of surface properties. We conclude that thrombin interactions with adsorbed fibrinogen determine the extent of subsequent fibrin proliferation on surfaces.

Adsorption↗
PubMed1997

Integrin alphaIIb beta3 reconstituted into lipid bilayers is nonclustered in its activated state but clusters after fibrinogen binding.

Integrin activation, ligand binding, and integrin clustering were analyzed using alphaIIb beta3 reconstituted into phospholipid vesicles and into supported planar lipid bilayers. Strong and specific binding of fibrinogen and the gamma-chain dodecapeptide of fibrinogen to alphaIIb beta3 indicated that the integrin is in an activated state after membrane reconstitution. Cryoelectron and fluorescence microscopy suggested a nonclustered state of the protein in the vesicle membrane. Supported planar lipid membranes were generated by fusion of vesicles in which approximately equal fractions of integrins were pointing inside-out and outside-in. This distribution led to an immobilization of about 40% of the integrin in supported bilayers due to attachment of the large extracellular domains to the quartz support. Fluorescence recovery after photobleaching indicated a diffusion coefficient of D = (0.70 +/- 0.06) x 10(-8) cm2/s, consistent with a nonclustered state of the mobile integrin. Upon fibrinogen binding, the integrins became immobile, and fluorescence micrographs showed a patchy distribution of fibrinogen-integrin complexes consisting of approximately 250 molecules. In addition to the expected dimer formation by bivalent fibrinogen, additionally induced fibrinogen clustering may account for the large size of the complexes. In contrast, binding of monovalent GRGDS pentapeptide or the gamma-chain dodecapeptide of fibrinogen altered neither the mobile fraction nor the association state of alphaIIb beta3. Our data indicate that integrin alphaIIbb3 is activated while monodisperse, and became clustered upon fibrinogen binding, leading to an irreversibly bound state.

Amino Acid Sequence↗
PubMed1996

High-level expression of recombinant human fibrinogen in the milk of transgenic mice.

Fibrinogen is a complex plasma protein composed of two each of three different polypeptide chains. We have targeted expression of r-human fibrinogen to the mammary gland of transgenic mice. Three expression cassettes, each containing the genomic sequence for one of the three human fibrinogen chains controlled by sheep whey protein beta-lactoglobulin promoter sequences, were coinjected into fertile mouse eggs. Southern blot analysis demonstrated that more than 80% of the transgenic founders contained all three fibrinogen genes. Reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis of milk from the highest producing founder animal demonstrated the presence of human fibrinogen subunits at concentrations of 2000 micrograms/ml. In several animals with a balanced ratio of the individual fibrinogen subunits, up to 100% of the protein was incorporated into fully assembled fibrinogen hexamers. Incubation of the transgenic milk with thrombin and factor XIII resulted in a cross-linked fibrin clot, indicating that a major portion of the secreted fibrinogen was functional. These studies represent the first report of high-level biosynthesis and secretion of a functional, complex, hexameric protein in the milk of a transgenic animal.

Animals↗
PubMed1967

Amino acid composition of human fibrinogen and anticoagulant derivatives.

1. The amino acid compositions of human fibrinogen and three intermediate anticoagulant derivatives were determined by column chromatography. The derivatives were isolated by ammonium sulphate fractionation and column electrophoresis from solutions of fibrinogen undergoing spontaneous breakdown. One derivative, isolated as the large electrophoretic peak at the end of the clottable period (100% CP) of the parent fibrinogen solution, was labelled LP(100) and others obtained at twice this period (200% CP) were designated as LP(200) and SP(200) (LP, large peak; SP, small peak). 2. Maximal ;molecular' weights of approx. 294000 for LP(100), 137000 for LP(200) and 37000 for SP(200) were calculated for the protein moieties. At least 265 amino acid residues must have been lost from each fibrinogen molecule during the formation of LP(100), and 1362 during the formation of the other two derivatives. 3. Only one derivative (LP(200)) had a partial specific volume ([unk] 0.725ml./g.) different from that of fibrinogen ([unk] 0.721ml./g.). 4. No significant differences in refractive index at 589mmu were detected. 5. Calculation of the total number of ionizable groups/10(5)g. of each protein moiety showed a preponderance of the following numbers of negative charges: 22 in fibrinogen; 24 in LP(100); 26 in LP(200); 49 in SP(200). The isoionic points were estimated to be approx.+0.03pH unit (for fibrinogen), -0.06pH unit for (LP(100)) and +0.28pH unit (for LP(200)) from the pK of imidazole, and 0.78pH unit above the average pK of aspartyl and glutamyl ions (for SP(200)). These figures agree closely with experimentally determined values of the isoelectric point of fibrinogen and its derivatives.

Amino Acids↗
PubMed1993

Effect of temperature on the association step in thrombin-fibrinogen interaction.

Kinetics of fibrinopeptide A release by human alpha-thrombin at low fibrinogen concentration allowed us to measure the specificity constant, i.e. kcat/Km, for the interaction between the enzyme and human fibrinogen. A study of the dependence of the ratio kcat/Km upon the viscosity of the medium revealed that fibrinogen acts as a 'sticky' substrate, or, in other words, as a substrate that dissociates from the Michaelis complex with a rate comparable with that for acylation of the active site. These experiments allowed us also to compute for the first time the second-order rate constant for thrombin-fibrinogen association. A study of the temperature-dependence of the association rate, carried out over the temperature range spanning from 10 degrees C to 37 degrees C (pH 7.50; I0.15) permitted the estimation of the enthalpy and entropy of activation, delta H++ and delta S++, which were found to be equal to 5.69 +/- 0.77 kJ.mol-1 and -80.25 +/- 1.79 kJ.K-1.mol-1 respectively. In addition, the values of Km for thrombin-fibrinogen reaction were measured at different solution viscosities in order to derive the equilibrium dissociation constant, Ks, of this interaction. These experiments showed that the Ks values for thrombin-fibrinogen binding was equal to 1.8 microM at 25 degrees C. Altogether these results indicated that fibrinogen, though interacting with both the catalytic pocket and the fibrinogen recognition site on the thrombin molecule, dissociates from Michaelis complex with a rate comparable with that shown by amide substrates, which interact only with the catalytic site.

Acylation↗
PubMed2002

G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis.

BACKGROUND: Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta-chain (FGB G-455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis. MATERIALS AND METHODS: We performed a case-control study including 307 patients with documented deep venous thrombosis and 316 control subjects. beta-fibrinogen genotypes were determined by allele-specific polymerase chain reaction. RESULTS: GG, GA and AA genotype frequencies were similar among the patients (53.1%, 41.0, 5.9) and controls (51.6%, 42.1, 6.3; P = 0.92). Fibrinogen levels of the patients (median 3.72 g l-1; range 1.93-11.6) did not differ significantly from those of the controls (3.76; 2.17-9.99). Carriers of the homozygous AA genotype had significantly higher fibrinogen levels than noncarriers (patients: 5.32 vs. 3.59; P = 0.024; controls: 6.29 vs. 3.72; P = 0.048). CONCLUSION: Our data suggest that the fibrinogen-elevating FGB G-455A gene polymorphism is not linked to an increased risk for deep venous thrombosis.

Alleles↗
PubMed1999

Fibrinogen and mortality in chronic critical limb ischaemia.

OBJECTIVE: Plasma fibrinogen predicts cardiovascular events in patients with stable peripheral arterial occlusive disease, but its predictive value in patients with chronic critical limb ischaemia, a condition associated with a high risk of death, is unknown. DESIGN: A prospective cohort study. SETTING: Determination of fibrinogen and other potential predictors during clinic-based work-up of patients admitted for diagnostic and therapeutic evaluation. SUBJECTS: A total of 108 patients (72 +/- 10 years, 78 males) with atherosclerotic occlusive disease and critical limb ischaemia (pain at rest and/or trophic lesions) followed up for a median period of 1.6 years). (range: 8 days-5.5 years; 218 patient-years). MAIN OUTCOME MEASURES: Total mortality. RESULTS: Forty-five deaths (71% cardiovascular) occurred during the follow-up. Baseline fibrinogen was higher in those who died in the early follow-up period (first 6 months), as were white cell count and serum creatinine, while haematocrit was lower. Plasma fibrinogen values correlated positively with white cell count, and negatively with haematocrit; other cardiovascular prognostic factors did not differ. Only plasma fibrinogen predicted survival independently in multivariate age-corrected Cox regression analysis. Relative risk of death doubled for each standard deviation above the mean and increased with each tertile increase in fibrinogen. CONCLUSIONS: Fibrinogen predicted death in these elderly arteriopaths with critical limb ischaemia, particularly those who died in the first months following critical ischaemia. Inflammatory stimuli secondary to severely defective tissue oxygenation and possibly sepsis and necrosis, might have stimulated fibrinogen, an acute-phase reactant, thereby compromising organ perfusion through increased blood viscosity and/or promoting thrombosis.

Aged↗
PubMed1998

Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus.

The surface-located fibrinogen-binding protein (clumping factor; ClfA) of Staphylococcus aureus has an unusual dipeptide repeat linking the ligand binding domain to the wall-anchored region. Southern blotting experiments revealed several other loci in the S. aureus Newman genome that hybridized to a probe comprising DNA encoding the dipeptide repeat. One of these loci is analysed here. It also encodes a fibrinogen-binding protein, which we have called ClfB. The overall organization of ClfB is very similar to that of ClfA, and the proteins have considerable sequence identity in the signal sequence and wall attachment domains. However, the A regions are only 26% identical. Recombinant biotinylated ClfB protein bound to fibrinogen in Western ligand blots. ClfB reacted with the alpha- and beta-chains of fibrinogen in the ligand blots in contrast to ClfA, which binds exclusively to the gamma-chain. Analysis of proteins released from the cell wall of S. aureus Newman by Western immunoblotting using antibody raised against the recombinant A region of ClfB identified a 124 kDa protein as the clfB gene product. This protein was detectable only on cells that were grown to the early exponential phase. It was absent from cells from late exponential phase or stationary phase cultures. Using a clfB mutant isolated by allelic replacement alone and in combination with a clfA mutation, the ClfB protein was shown to promote (i) clumping of exponential-phase cells in a solution of fibrinogen, (ii) adherence of exponential-phase bacteria to immobilized fibrinogen in vitro, and (iii) bacterial adherence to ex vivo human haemodialysis tubing, suggesting that it could contribute to the pathogenicity of biomaterial-related infections. However, in wild-type exponential-phase S. aureus Newman cultures, ClfB activity was masked by the ClfA protein, and it did not contribute at all to interactions of cells from stationary-phase cultures with fibrinogen. ClfB-dependent bacterial adherence to immobilized fibrinogen was inhibited by millimolar concentrations of Ca2+ and Mn2+, which indicates that, like ClfA, ligand binding by ClfB is regulated by a low-affinity inhibitory cation binding site.

Adhesins, Bacterial↗
PubMedDate not supplied

Fibrinogen in cryoprecipitate and its relationship to factor VIII (AHF) levels.

Very little has been published to indicate the quantity of fibrinogen in cryoprecipitates. We assayed 88 preparations from five blood banks for factor VIII(AHF) and fibrinogen to assess whether the AHF assay can predict the fibrinogen content. Cryoprecipitate was considered to be consistent with FDA standards with 80 units of factor VIII/bag (40% yield from 200 ml plasma). Fibrinogen was considered adequate if 200 mg were recovered (40% yield, 200 ml plasma, normal range 150--350 mg/dl). The mean AHF was 145 units/bag and fibrinogen. In 64/88 bags, the fibrinogen and AHF were concordant, but in 24/88 bags the results were discordant. Although it appears safe to conclude that a bag of cryoprecipitate will average 250 mg fibrinogen, adequate control may require separate assays for fibrinogen.

Chemical Precipitation↗
PubMed1998

Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study.

AIMS: Fibrinogen was measured in 5095 men and 4860 men aged 40-59 in a random population sample from 25 districts of Scotland recruited during 1984-87: the Scottish Heart Health Study. Fibrinogen was then related to the chance of fatal and non-fatal coronary events and death from any cause during a subsequent follow-up period of around 8 years. METHODS AND RESULTS: Fibrinogen was measured by the Clauss assay. The effect of fibrinogen on coronary heart disease and death was assessed through age-adjusted means and Cox proportional hazards regression models, accounting for age, cotinine (a measure of tobacco smoke inhalation) and 11 other major coronary risk factors. Fibrinogen was found to be an important risk factor for coronary heart disease in men and women, with and without pre-existing coronary heart disease. There appears to be a threshold effect, with those in the highest fifth of the distribution having a much increased risk. Estimated age-adjusted hazard ratios by sex and pre-existing coronary heart disease group for the highest to lowest fifth of fibrinogen range between 1.93 and 4.86. Fibrinogen is also important as a risk factor for coronary death and all-causes mortality, with a similar threshold effect. Comparing the two extreme fifths, the hazard ratios for coronary death are 3.01 and 3.42, and for all-cause mortality are 2.59 and 2.20, for men and women respectively. Adjustment for cotinine reduces the hazard ratios, but further adjustment for the other 11 risk factors has little effect for coronary heart disease events. After full adjustment there is a remaining significant (P < 0.05) hazard ratio for coronary death and death from any cause and for a coronary heart disease event for those free of coronary heart disease at baseline, amongst men, comparing the highest to the lowest fifth. CONCLUSION: Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women. Its effect is only partially attributable to other coronary risk factors, the most important of which is smoking.

Adult↗
PubMed1978

Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule.

Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.

Blood Coagulation Disorders↗