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PubMed1992

Adsorption of baboon fibrinogen and the adhesion of platelets to a thin film polymer deposited by radio-frequency glow discharge of allylamine.

Platelet adhesion under static and flow conditions from a washed platelet suspension containing albumin to a polymer deposited by radio-frequency glow discharge of allylamine vapour on a poly(ethylene terephthalate) substrate was measured. Electron spectroscopy for chemical analysis was used to characterize the surface. Fibrinogen adsorption from a series of dilute plasma solutions to radio-frequency glow discharge/allylamine, measured using 125I radiolabelled baboon fibrinogen, increased with decreasing plasma dilution to a level much higher than that previously observed on polyurethanes. Elutability by sodium dodecyl sulphate of fibrinogen adsorbed from dilute plasma also increased with increasing plasma concentration, but fibrinogen preadsorbed from plasma became non-elutable when surfaces were stored in buffer for 5 d before contact with sodium dodecyl sulphate. Platelet adhesion to substrates which had been pre-adsorbed with dilute plasma was measured using baboon platelets radiolabelled with 111In. Adhesion greatly decreased as the plasma concentration used for preadsorption increased, suggesting that non-specific platelet binding to the bare surface occurs when protein coverage is incomplete. Non-specific platelet binding was inhibited to varying degrees by preadsorption of different proteins to the surface. Platelet adhesion to surfaces preadsorbed with dilute (1.0%) baboon and human plasmas lacking fibrinogen (i.e. serum, heat-defibrinogenated plasma and congenitally afibrinogenemic plasma) was diminished compared with normal plasma. Addition of exogenous fibrinogen to the deficient plasma partially restored platelet adhesion to normal levels. Adhesion to surfaces preadsorbed with human plasma deficient in von Willebrand factor was comparable to that observed with normal plasma. The plasma preadsorption studies with fibrinogen deficient media suggested that adsorbed fibrinogen is necessary for platelet adhesion to the radio-frequency glow discharge/allylamine substrate at high protein coverage. However, since adhesion was greatly reduced when the plasma preadsorbed substrate was stored in buffer before platelet contact, the conformation of adsorbed fibrinogen is also important in mediating platelet adhesion to radio-frequency glow discharge.

Adsorption↗

PubMed1982

Sequence content of alpha-fetoprotein, albumin and fibrinogen polypeptide mRNAs in different organs, developing tissues and in liver during carcinogenesis in rats.

To investigate the variable gene activities of alpha-fetoprotein, albumin and fibrinogen polypeptides as markers of 'liver specific proteins' in different developing organs or tissues, we have used specific complementary DNA probes to detect and to quantitate alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA, respectively, in RNA fractions, prepared from various tissues of rats at different stages of fetal and postnatal development and from hepatomas induced by diethylnitrosamine. The results indicate that there is no consistent relationship between sequence content of alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA in different developing tissues. Intestines which are like the liver also of endodermal origin do not contain alpha-fetoprotein, albumin and fibrinogen polypeptide mRNAs, while kidneys which are mesodermal in origin were found to be alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA producers in neonatal life. In yolk sac, only alpha-fetoprotein and fibrinogen polypeptide mRNA could be detected. In the liver, the increased level of albumin and fibrinogen polypeptide mRNA during fetal and neonatal development is accompanied with a diminished amount of alpha-fetoprotein mRNA. The neosynthesis of alpha-fetoprotein mRNA in the liver during carcinogenesis occurred without a decreased content of albumin and fibrinogen polypeptide mRNAs. These findings suggest that complex mechanisms of gene regulation are involved in variable gene activities of alpha-fetoprotein, albumin and fibrinogen polypeptides in cells of different organs or tissues developed from a single cell.

Aging↗

PubMed1983

Structural and chromatographic heterogeneity of normal plasma fibrinogen associated with the presence of three gamma-chain types with distinct molecular weights.

Three different gamma chains have been identified in fibrinogen isolated from normal human plasma with apparent molecular weights of 50000 (gamma 50), 55000 (gamma 55) and 57500 (gamma 57.5), as shown by SDS-polyacrylamide gel electrophoresis. Plasma fibrinogen was separated by ion-exchange chromatography on DEAE-Sephacel into three populations of molecules, each differing in gamma-chain composition. The first peak contained 87% of the total fibrinogen and was composed of molecules containing only gamma 50 chains; the second peak included 3% of the fibrinogen and contained one gamma 50 and one gamma 55 chain, and the third peak had 10% of the total which contained one gamma 50 and one gamma 57.5 chain. Cross-linked fibrin obtained from fibrinogen with only gamma 50 chains contained gamma gamma dimers exclusively of Mr 100000, representing a uniform gamma 50 gamma 50 dimer composition. The gamma gamma dimers from purified fibrinogen of gamma 50 gamma 55 type had molecular weights of 111000, 105000 and 100000, while dimers from gamma 50 gamma 57.5 fibrinogen were of Mr 115000, 108000 and 100000. The relative proportions of gamma gamma dimers from each purified fibrinogen population were consistent with random crosslinking of the gamma monomers. The gamma-chain identity of the variants was established by their conversion to covalent dimeric species after clotting by thrombin in the presence of Factor XIII, their incorporation of the fluorescent lysine analog dansyl cadaverine, by the staining intensity of monomeric and dimeric forms with the periodic acid-Schiff reagent after electrophoretic separation, and by plasmic degradation of all monomeric and dimeric forms in a pattern that was characteristic for gamma chains. Individual gamma gamma dimers were purified by preparative gel electrophoresis, and tyrosine was demonstrated to be the amino-terminal residue of all three gamma chain types. We conclude that normal human fibrinogen can be separated into three populations of molecules due to molecular weight heterogeneity of their gamma chains.

Chromatography, Ion Exchange↗

PubMed1991

Inhibition of platelet aggregation by a fibrinogenase from Naja nigricollis venom is independent of fibrinogen degradation.

Fibrinogenases, proteinases which release peptides from the carboxy-terminal end of fibrinogen, are classified as alpha-fibrinogenases or beta-fibrinogenases, based on their ability to preferentially attack the A alpha or B beta chain, respectively, of fibrinogen. alpha-Fibrinogenases have been shown to inhibit platelet aggregation whereas beta-fibrinogenases do not. We have studied the inhibition of platelet aggregation by proteinase F1, an alpha-fibrinogenase from Naja nigricollis venom. This proteinase inhibits whole blood aggregation in a dose-dependent manner, with an IC50 value of 145 micrograms. However, the proteinase fails to inhibit aggregation in washed platelet suspensions. Thus, proteinase F1 appears to require a plasma factor to cause inhibition. Since fibrinogen acts as an adhesive protein which links platelets during aggregation, and since proteinase F1 cleaves fibrinogen, we investigated the role of fibrinogen in the inhibition of platelet aggregation by proteinase F1. The degradation products of fibrinogen formed by the proteinase did not cause significant inhibition. Thus, the inhibition of platelet aggregation appears to be independent of the formation of fibrinogen degradation products. We also studied the effect of proteinase F1 on aggregation of platelets that were reconstituted with defibrinogenated plasma. The proteinase inhibited aggregation of platelets even in the absence of plasma fibrinogen. Proteinase F1 was about 4-fold more potent in inhibiting platelet aggregation in defibrinogenated blood. From these results, we conclude that the inhibition of platelet aggregation by proteinase F1 from N. nigricollis venom is independent of its action on fibrinogen.

Animals↗

PubMed1995

Plasma fibrinogen levels and their correlates in 6457 coronary heart disease patients. The Bezafibrate Infarction Prevention (BIP) Study.

The association between fibrinogen measured in healthy individuals and subsequent development of ischemic heart disease is well established, but studies reporting fibrinogen levels in coronary heart disease patients are scarce. Plasma fibrinogen was determined for 5729 men and 728 women (aged 45 to 74) with established coronary heart disease, screened for participation in the Bezafibrate Infarction Prevention study, with the following lipid profile at the time of the first screening visit: total serum cholesterol < or = 270 mg/dl, high density lipoprotein cholesterol < or = 45 mg/dl and triglyceride < or = 300 mg/dl. Increased age was associated with augmented plasma fibrinogen values. Age-adjusted fibrinogen levels were higher in women than in men. A direct association was found between mean fibrinogen levels and low density lipoprotein cholesterol. On the other hand, the correlation with high density lipoprotein cholesterol was inverse. Fibrinogen was also associated with body mass index, behavioral variables and severity of coronary heart disease. In a multivariable linear regression analysis performed, risk factors considered explained merely 6 and 4% of fibrinogen variation for men and women, respectively. Therefore, most of the fibrinogen level variability in coronary heart disease patients is accounted for by factors that remain to be established by further research.

Age Factors↗

PubMed2002

Quantitative RT-PCR analysis demonstrates that synthesis of the recombinant fibrinogen is dependent on the transcription and synthesis of gamma-chain.

BACKGROUND: The purpose of this study was to examine the relationship between the production of secreted fibrinogen and the synthesis of gamma-chain mRNA. METHODS: We transfected a gamma-chain expression vector into Chinese hamster ovary cells already expressing both Aalpha- and Bbeta-chains of fibrinogen and measured fibrinogen output concentrations by ELISA. We quantified both gamma-chain and Bbeta-chain mRNA concentrations using the recently developed TaqMan fluorogenic detection system. RESULTS: The concentration of secreted fibrinogen into the media positively correlated with the amount of fibrinogen contained in the cell lysates. Additionally, quantitative mRNA assays revealed that the fibrinogen concentration in the cell lysates correlated well with the concentration of gamma-chain mRNA (r=0.7077, p<0.01) but not with the concentration of Bbeta-chain mRNA (r=0.0224, NS). CONCLUSIONS: These results demonstrate that the amount of recombinant fibrinogen produced in cells transfected with the gamma-chain vector, also expressing normal Aalpha- and Bbeta-chains, is dependent on the transcription of gamma-chain mRNA. Namely, in this recombinant expression system using a two-step transfection procedure, gamma-chain synthesis is the rate-limiting factor for fibrinogen production. This quantitative method to measure mRNA may prove very useful for further in vivo analysis of fibrinogen gene transcription.

Amino Acid Sequence↗

PubMed1999

Fibrinogen gene polymorphism in a non-Caucasian population.

OBJECTIVE: The purpose of this study was to investigate the two polymorphisms of fibrinogen gene (RsaI and MnlI RFLPs in the coding region of the fibrinogen gene) in Koreans, and their relation to plasma fibrinogen. METHODS: Using PCR-amplified DNAs, RsaI and MnlI RFLPs were analyzed in 112 patients with coronary artery disease (CAD) and 137 healthy subjects. To compare the mean of plasma fibrinogen and lipid levels among different genotypes, one-way analysis of variance (ANOVA) test was performed. RESULTS: Allele frequencies of fibrinogen gene polymorphism in Koreans were not significantly different between CAD and control groups; fibrinogen polymorphism in this population showed a lack of association with plasma fibrinogen levels, but significant association with BMI (p < 0.05). CONCLUSION: This evidence suggests that in Korean populations, fibrinogen gene polymorphism is not a factor in the expression of atherosclerosis. There might, however, be an association between fibrinogen gene and obesity in such population.

Aged↗

PubMed2001

Fibrinogen is an antioxidant that protects beta-lipoproteins at physiological concentrations in a cell free system.

Oxidation of beta-lipoproteins has been linked to the development of arteriosclerosis. Using a copper mediated cell free system to oxidize beta-lipoproteins, we found that beta -lipoproteins isolated from plasma were less susceptible to oxidation than lipoproteins from serum and that this was probably due to inhibition by fibrinogen, because removal of fibrinogen from plasma enhanced oxidation, while addition of fibrinogen restored inhibition. Fibrinogen inhibited conjugated diene formation and peroxide formation assayed by the xylenol orange assay (absorbance+/-confidence interval: 0.155+/-0.007 with fibrinogen vs 0.255+/-0.014 without) and retarded copper mediated oxidation of apolipoproteins in low density lipoproteins, reducing the distance of electrophoretic migration by 5 mm. The effect of fibrinogen was not due to chelation of copper, since it provided protection when hydrogen peroxide was substituted for copper as an oxidizing agent. At normal physiological concentration equivalents, fibrinogen showed superior antioxidant properties compared to albumin, melatonin, vitamin C and vitamin E and was superior to the vitamins when compared on an equimolar basis. Other studies have shown the fibrinogen to be more oxidizable than other major plasma proteins and to inhibit peroxide production. Because of its high mass concentration, we postulate fibrinogen is an important antioxidant protecting beta-lipoproteins in plasma and that it may be important in protecting lipoproteins in tissue spaces.

Antioxidants↗

PubMed2003

Induced removal of dipalmitoyl phosphatidylcholine by the exclusion of fibrinogen from compressed monolayers at air/liquid interfaces.

The induced removal of dipalmitoyl phosphatidylcholine (DPPC) by the exclusion of fibrinogen from mixed DPPC/fibrinogen monolayers at compressed air/liquid interfaces was analyzed. The surface pressure-area hysteresis curves of the monolayers at interfaces were obtained by a Langmuir trough. The hysteresis curves of equilibrium fibrinogen adsorption layers suggest that fibrinogen desorption during the area compression stage became significant at a higher bulk concentration of 1000 ppm. For mixed monolayers of DPPC with fibrinogen, the fibrinogen molecules were expelled from the interface upon compression due to the presence of insoluble DPPC molecules. The squeeze-out of fibrinogen molecules evidently removed a significant number of DPPC molecules from the interface, with the extent depending on fibrinogen surface concentration. During the subsequent area expansion stage, fibrinogen molecules entered the interface and participated in the rise of surface pressure. The induced loss of free DPPC molecules at the interface by the expelled fibrinogen molecules during the area compression stage was then evaluated from the hysteresis curves.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

Thrombotic dysfibrinogenemia. Fibrinogen "Caracas V" relation between very tight fibrin network and defective clot degradability.

Fibrinogen Caracas V is a thrombotic dysfibrinogenemia with an Aalpha 532 Ser-->Cys mutation characterized by a tight fibrin network formed of thin fibers responsible for a less porous clot than a normal one. In the present work, fibrinogen Caracas V is further characterized in order to understand the relationship between the structural defect and thrombophilia. This thrombotic disorder has been attributed to a tight fibrin network responsible for a decreased permeation of flow through the clot, leading to defective thrombus lysis due to a diminished availability of fibrinolytic enzymes to the inner fibrin surface. Correction of clot structure anomaly, by addition of dextran 40 to fibrinogen before clotting, induces an improvement in fibrin degradation that was attributed to an increase in porosity. The pulmonary embolism observed in this family has been related to an hyper rigidity of the clot, an anomaly that is also corrected by dextran. Furthermore, this abnormal fibrinogen binds more albumin than does normal fibrinogen, a phenomenon attributed to the mutation of serine in Aalpha-532 by cysteine. Therefore, this fibrinogen shows a striking similarity to the fibrinogen Dusart, allowing us to confirm that the alphaC-terminal part of fibrinogen plays an important role in fibrin structure, and to conclude that the anomaly of fibrin network observed in fibrinogen Caracas V is responsible for a deficient thrombus lysis.

Albumins↗

PubMed2000

Fibrinogen fractions in the third trimester of pregnancy and in puerperium.

The concentration of fibrinogen, its fractions, and the concentration of C-reactive protein were determined in 45 healthy pregnant women before and after vaginal (27) or caesarean section 18 delivery. The control group consisted of 33 blood donors. In pregnancy, increased concentration of total fibrinogen and its fractions and a normal concentration of C-reactive protein were noted. Three days after vaginal delivery the concentration of total and high molecular weight fibrinogen fraction decreased slightly and the ratio of high to low molecular weight fibrinogen increased. After caesarean section both total and high molecular weight fibrinogen and the ratio of high to low molecular weight fibrinogen increased. The C-reactive protein concentration increased after either type of delivery. The degree of augmentation, however, was ten times as strong after caesarean section. In all women at the end of puerperium the concentrations of the compounds studied returned to normal values. The results suggest that the mechanisms leading to the increase of fibrinogen during pregnancy and after delivery are different. The increase of all fibrinogen fractions in pregnancy may depend first of all on hormones, whereas the increased proportion of high molecular weight to low molecular weight fibrinogen after delivery depends on the acute phase reaction. The degree of this reaction depends on the type of delivery.

Adult↗

PubMed1998

Movement of fibrinogen receptors on the ventral membrane of spreading platelets.

We have used fibrinogen gold conjugates and fluorescein-labelled fibrinogen to examine the presence of fibrinogen receptors on the ventral membrane of spreading platelets and to visualize the redistribution of the receptors during platelet spreading. The movement of fibrinogen gold conjugates was observed in real time using video-enhanced interference reflection microscopy (VEIRM) and the redistribution of fluorescein-labelled fibrinogen was examined using video-intensified epifluorescence microscopy (VIFM). Fibrinogen was picked up by spreading platelets and moved towards the centre of the platelets. The velocity of the movement of fibrinogen-gold conjugates under the ventral membrane ranged from less than 0.1 microm min(-1) to more than 10 microm min(-1). The average velocity in the peripheral web region was more than 6 microm min(-1), and was reduced to around 1 microm min(-1) in the outer and inner filamentous zones. The centralized fibrinogen molecules were internalized and eventually removed from the platelets. Video microscopy in conjunction with colloidal gold particles provides a simple method for real-time observation of the movement of fibrinogen receptors on the ventral membrane of spreading platelets.

Adsorption↗

PubMed1998

Protein and platelet interactions with thermally denatured fibrinogen and cross-linked fibrin coated surfaces.

In this work the hypothesis that a mature, cross-linked fibrin clot, pre-formed on a biomaterial, may be relatively nonthrombogenic was investigated. A cross-linked fibrin layer was formed on polyethylene which had been precoated with thermally denatured fibrinogen. Plasma protein adsorption and platelet interactions with the cross-linked fibrin and denatured fibrinogen surfaces were investigated. The adsorption of albumin, fibrinogen, and fibronectin from plasma was measured. For all three proteins, the cross-linked fibrin surface exhibited much higher levels of adsorption than either the thermally denatured fibrinogen or the polyethylene surface. Vroman peaks were observed for fibrinogen and fibronectin on polyethylene but not on the cross-linked fibrin and thermally denatured fibrinogen materials. In dilute plasma the thermally denatured fibrinogen surface showed considerable resistance to protein adsorption. However, at plasma concentrations greater than about 5% normal, this protein resistance was apparently lost. Platelet interactions (adhesion and release of granule constituents from adherent platelets) using suspensions of washed platelets in the presence of red cells were investigated at shear rates of 50, 300, and 525 s(-1) using a cone and plate apparatus. The levels of platelet adhesion on the different surfaces were in the order: adsorbed fibrinogen > cross-linked fibrin > thermally denatured fibrinogen = polyethylene. Platelets on the cross-linked fibrin surface also showed high levels of release indicating significant platelet activation. Scanning electron microscopic observations were in agreement with the platelet adhesion and release data, showing only a few (but well-spread) adherent platelets on the cross-linked fibrin surface.

Adsorption↗

PubMed2006

Multiple interactions of FbsA, a surface protein from Streptococcus agalactiae, with fibrinogen: affinity, stoichiometry, and structural characterization.

Streptococcus agalactiae is an etiological agent of several infective diseases in humans. We previously demonstrated that FbsA, a fibrinogen-binding protein expressed by this bacterium, elicits a fibrinogen-dependent aggregation of platelets. In the present communication, we show that the binding of FbsA to fibrinogen is specific and saturable, and that the FbsA-binding site resides in the D region of fibrinogen. In accordance with the repetitive nature of the protein, we found that FbsA contains multiple binding sites for fibrinogen. By using several biophysical methods, we provide evidence that the addition of FbsA induces extensive fibrinogen aggregation and has noticeable effects on thrombin-catalyzed fibrin clot formation. Fibrinogen aggregation was also found to depend on FbsA concentration and on the number of FbsA repeat units. Scanning electron microscopy evidentiated that, while fibrin clot is made of a fine fibrillar network, FbsA-induced Fbg aggregates consist of thicker fibers organized in a cage-like structure. The structural difference of the two structures was further indicated by the diverse immunological reactivity and capability to bind tissue-type plasminogen activator or plasminogen. The mechanisms of FbsA-induced fibrinogen aggregation and fibrin polymerization followed distinct pathways since Fbg assembly was not inhibited by GPRP, a specific inhibitor of fibrin polymerization. This finding was supported by the different sensitivity of the aggregates to the disruptive effects of urea and guanidine hydrochloride. We suggest that FbsA and fibrinogen play complementary roles in contributing to thrombogenesis associated with S. agalactiae infection.

Bacterial Proteins↗

PubMed1996

Alternative adhesion sites in human fibrinogen for vascular endothelial cells.

Fibrinogen mediates endothelial cell adhesion, spreading, and angiogenesis through integrin alphavbeta3. Previous studies by several investigators have suggested that the Arg-Gly-Asp (RGD) site at position 572-574 on the alpha chain of human fibrinogen can bind to alphavbeta3. However, this RGD sequence is absent in fibrinogen from most other species, including bovine, hamster, monkey, mouse, pig, and rat fibrinogen. In these species, an RGD site exists at the equivalent of position alpha252-254, which has the sequence RGG in humans. In addition, the role of an integrin binding site on the gamma chain at position 400-411 has been an issue of controversy. In the present studies, recombinant fibrinogen molecules with mutations in the potential endothelial cell binding sites have been used to test the role of these sites directly. The results show that the RGD at alpha572-574 is the primary adhesion site, and that the gamma chain site plays no significant role. Human and bovine plasma fibrinogens were also assayed for their ability to support adhesion of human and bovine vascular endothelial cells. The results show that although the two types of fibrinogen have RGD sequences at widely divergent sites, there is no significant difference in their ability to support endothelial cell adhesion. Furthermore, a chimeric human fibrinogen molecule with an RGD sequence at the bovine site, position alpha252-254, also supported adhesion. These results indicate that an RGD site in human fibrinogen at either position alpha252-254 or position alpha572-574 can mediate endothelial cell adhesion.

Amino Acid Sequence↗

PubMed1998

Analysis of A alpha 251 fibrinogen: the alpha C domain has a role in polymerization, albeit more subtle than anticipated from the analogous proteolytic fragment X.

Numerous experiments have demonstrated that the C-terminal domain of the fibrinogen Aalpha-chain, the alphaC domain, has a role in polymerization. To further examine the role of this domain, we synthesized a recombinant fibrinogen, Aalpha251 fibrinogen, that lacks the alphaC domain. We examined thrombin-catalyzed fibrinopeptide release and found that the rate of FpB release from Aalpha251 fibrinogen was 2.5-fold slower than FpB release from normal fibrinogen, while the rate of FpA release was the same for both proteins. We examined thrombin-catalyzed polymerization and found that the rates of protofibril formation and lateral aggregation were similar for both proteins, although discernible differences in lateral aggregation were clear. The rate of protofibril formation for Aalpha251 fibrinogen was never less than 85% of normal fibrinogen, while the rate of lateral aggregation for Aalpha251 fibrinogen varied from 64 to 74% of normal. We examined polymerization of fibrin monomers and found that polymerization of Aalpha251 fibrin was similar to normal fibrin at 0.4 M NaCl, but clearly different from normal at 0.05 M NaCl. These results indicate that the alphaC domain has a role in lateral aggregation, but this role is more subtle than anticipated from previous experiments, particularly those with fibrinogen fragment X. We interpret this unanticipated finding as indicative of an important contribution from the N-terminus of the beta-chain, such that protein heterogeneity that includes small amounts of fibrin lacking that N-terminus of the beta-chain leads to markedly altered lateral aggregation.

Animals↗

PubMed1997

Elevated fibrinogen levels decrease following treatment of acromegaly.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality from cardiovascular disease and from stroke in particular. Fibrinogen is an established risk factor for stroke and myocardial infarction and high levels of plasminogen activator inhibitor-1 (PAI-1) activity were predictive of a recurrent myocardial infarction. The aim of this study was to analyse fibrinogen and PAI-1 activity in patients with acromegaly before and after treatment. PATIENTS: Twenty patients with acromegaly were compared with healthy controls matched for sex (12 men, 8 women), age (mean 53 +/- 7 years), body mass index (mean 26.5 +/- 2.5 kg/m2) and smoking. Fibrinogen was also compared with a random population sample of men and women (n = 392), aged 25-64 years, from the WHO's MONICA Project, Göteborg, Sweden. RESULTS: The acromegalic patients had a higher lean body mass of 65 +/- 11 vs 59 +/- 11 kg (P < 0.05), lower body fat of 17 +/- 8 vs 25 +/- 10 kg (P < 0.01), higher plasma fibrinogen of 4.0 +/- 0.9 vs 2.4 +/- 0.5 g/l (P < 0.001) and plasma insulin of 15 +/- 14 vs 7 +/- 2 mU/l (P < 0.01), serum triglycerides of 1.5 +/- 0.5 vs 1.2 +/- 0.5 mmol/l (P < 0.05), as well as serum insulin-like growth factor-I (IGF-I) levels of 742 +/- 271 vs 168 +/- 51 micrograms/l (P < 0.001) compared with the matched controls. PAI-1 activity was similar, as was total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose and blood pressure for acromegalic patients compared with controls. All the acromegalic patients had higher fibrinogen levels (p < 0.001) than the population mean. Plasma fibrinogen correlated positively with serum IGF-I in acromegaly (r = 0.55, P < 0.05). Fibrinogen decreased to a mean value of 3.2 +/- 0.3 g/l on treatment. CONCLUSION: Acromegaly is associated with high fibrinogen levels which may be one explanation for the increased risk of cardiovascular events, and stroke in particular, in this disease. Fibrinogen levels decreased following treatment of acromegaly.

Acromegaly↗

PubMed2003

Fibrinogen storage disease without hypofibrinogenaemia associated with acute infection.

AIMS: The presence of ground glass hepatocytes in a liver biopsy may be related to different conditions, including fibrinogen storage disease. Three types of fibrinogen storage disease have been described, namely types I, II and III. Type I is an hereditary hypofibrinogenaemia genetically characterized by a mutant variant of the fibrinogen molecule designated as fibrinogen Brescia, consistent with a gamma284 Gly-->Arg mutation. Only rare cases of types II and III fibrinogen storage disease have been described. The purpose of the present paper is to describe two cases of fibrinogen storage disease without associated hypofibrinogenaemia, which appeared during acute infectious diseases. METHODS AND RESULTS: Both patients were female, aged 77 and 73 years, who developed high transaminases during an infectious disease. In each case blood coagulation tests were within the normal range, and despite clinical and laboratory investigations no possible cause for liver disease could be found. Liver biopsies were performed; in both cases weakly eosinophilic cytoplasmic inclusions were observed. Using immunohistochemistry the inclusions were found to be due to fibrinogen accumulation. At ultrastructural level features corresponding to type II inclusions were observed. Molecular studies, performed in case 2, excluded the mutation typical of type I fibrinogen storage disease. Both patients also presented features of chronic hepatitis. In case 1, giant cell granulomas were additionally present. No close relatives of the patients presented any clinical or laboratory features of liver disease. In both patients altered liver function test values gradually, spontaneously, returned to within normal ranges after infectious disease was resolved. CONCLUSIONS: These cases suggest that, on rare occasions, hepatocytes may accumulate fibrinogen during an infectious disease.

Acute Disease↗