Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FIBRINOGEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1988

Interaction of fibrinogen with its platelet receptor. Differential effects of alpha and gamma chain fibrinogen peptides on the glycoprotein IIb-IIIa complex.

The platelet membrane glycoprotein IIb-IIIa complex (GPIIb-IIIa) recognizes peptides containing the amino acid sequence Arg-Gly-Asp, a sequence present at two locations in the alpha chain of fibrinogen. GPIIb-IIIa also interacts with peptides containing the carboxyl-terminal 10-15 residues of the fibrinogen gamma chain. We found that the alpha chain tetrapeptide, Arg-Gly-Asp-Ser (RGDS), and the gamma chain peptide, Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (LGGAKQAG-DV), each inhibited fibrinogen binding to ADP-stimulated platelets with Ki values of 15.6 +/- 2.7 and 46.2 +/- 8.2 microM, respectively. Furthermore, the inhibitory effect of the peptides was additive, indicating that they interact with GPIIb-IIIa in a mutually exclusive manner. Mutually exclusive binding suggests that either the alpha and gamma chain peptides bind to identical or overlapping sites on the GPIIb-IIIa complex or that one peptide induces a change in the complex that excludes the other. To differentiate between these possibilities, we compared the ability of RGDS and LGGAKQAGDV to inhibit the binding of fibrinogen and two GPIIb-IIIa complex-specific monoclonal antibodies, A2A9 and PAC-1, to ADP-stimulated platelets. A2A9 and PAC-1 appear to bind to different sites on GPIIb-IIIa because A2A9 binds to both stimulated and unstimulated platelets while PAC-1 only binds to stimulated platelets. RGDS specifically inhibited fibrinogen and PAC-1 binding with nearly identical Ki values of 15.6 +/- 2.7 and 20.2 +/- 3.5 microM, respectively. In contrast, LGGAKQAGDV had a differential effect on fibrinogen and PAC-1 binding, inhibiting PAC-1 binding with a Ki of 116.1 +/- 12.9 microM and fibrinogen binding with a Ki of 46.2 +/- 8.2 microM (p less than 0.005). Furthermore, while RGDS had no effect on the binding of the monoclonal antibody A2A9, LGGAKQAGDV was a partial inhibitor of A2A9 binding to activated platelets. These results suggest that the bindings sites for RGDS and LGGAKQAGDV are spatially distinct. They also suggest that ligand-induced changes in GPIIb-IIIa conformation are likely to be responsible for the mutually exclusive nature of alpha and gamma chain peptide binding.

Adenosine Diphosphate↗
PubMed1984

A murine monoclonal antibody that blocks fibrinogen binding to normal platelets also inhibits fibrinogen interactions with chymotrypsin-treated platelets.

We recently described a monoclonal antibody, 10E5 , that completely blocks adenosine diphosphate (ADP) induced fibrinogen binding to platelets and aggregation induced by ADP, epinephrine, and thrombin. Multiple lines of evidence indicate that 10E5 binds to platelet membrane glycoproteins IIb and/or IIIa. Because it has been reported that platelets treated with chymotrypsin aggregate when fibrinogen is added, we tested the effect of 10E5 antibody on chymotrypsin-induced fibrinogen binding and platelet aggregation. Aspirin-treated human platelets were washed in modified Tyrode's buffer (pH 7.5), incubated for 5 minutes at 22 degrees C with 300 micrograms/mL chymotrypsin, and washed again. The amount of 10E5 antibody bound to these platelets (37,232 +/- 2,928 molecules/platelet; mean +/- SEM, N=9) was similar to that bound to unstimulated control platelets (36,910 +/- 2,669) and did not differ significantly from the amount of antibody bound to ADP-treated platelets (P less than .01, N = 5). The amount of 10E5 bound to chymotrypsin-treated platelets correlated directly with the amount of fibrinogen bound to separate aliquots of the same platelet samples (r = .876, P less than .001). The 10E5 antibody caused virtually complete inhibition of both the binding of fibrinogen to chymotrypsin-treated platelets and the aggregation induced by exogenous fibrinogen. Immunoprecipitation studies of 125I-labeled chymotrypsin-treated platelets revealed that the 10E5 antibody bound proteins with molecular weights characteristic of glycoproteins IIb and IIIa. These data suggest that the fibrinogen receptor on chymotrypsin-treated platelets is identical to that on ADP-treated platelets and that this receptor is either near to, or on, the glycoprotein IIb/IIIa complex.

Animals↗
PubMed1981

Inhibitors of ADP-induced platelet aggregation prevent fibrinogen binding to rabbit platelets and cause rapid deaggregation and dissociation of bound fibrinogen.

125I-fibrinogen binds to washed rabbit platelets when they ar stimulated wit ADP, and it has previously been observed that fibrinogen binding is prevented by several inhibitors of ADP-induced aggregation. We have now shown that other inhibitors of aggregation, the phosphodiesterase inhibitors caffeine and dipyridamole, and colchicine and cytochalasin B which affect the platelet cytoskeleton, also inhibit specific 125I-fibrinogen binding. A positive correlation was observed between ADP-induced aggregation and fibrinogen binding at limiting concentrations of these inhibitors. Colchicine and cytochalasin B appear to act independently, with no indication of synergism. When any of these inhibitors, as well as those previously tested (EDTA, EGTA, PGE1 and PGI2) was added to platelets that had already been stimulated with ADP and undergone considerable aggregation and fibrinogen binding, it caused rapid deaggregation of the platelets and dissociation of bound fibrinogen, although in some cases the inhibitory effects were not as pronounced as when the inhibitor was added before ADP stimulation. These observations reinforce the concept that fibrinogen plays an essential role in the formation of ADP-induced platelet aggregates.

Adenosine Diphosphate↗
PubMed1993

The role of beta-fibrinogen genotype in determining plasma fibrinogen levels in young survivors of myocardial infarction and healthy controls from Sweden.

Beta-fibrinogen G/A-455 polymorphism genotype was determined in 123 young survivors of myocardial infarction and 86 healthy controls from Sweden. Frequency of the A-455 allele was 0.25 (95% Confidence Interval 0.21-0.29) in both patients and controls, significantly higher than that reported previously (0.19, 95% CI 0.16-0.22) in 292 men from the UK. Mean plasma fibrinogen level was significantly higher in patients (3.6 g/l) than in controls (3.1 g/l), with p < 0.001. Genotype was significantly associated with (adjusted) plasma fibrinogen level in controls (p = 0.003). This effect was confined to the smokers (n = 50) where mean fibrinogen level was significantly (p = 0.001) higher in G/A-455 and A/A-455 individuals (3.5 g/l) compared with G/G-455 homozygotes (2.9 g/l). There was a significant interaction between smoking status and genotype in determining plasma fibrinogen levels in the controls. These data provide independent confirmation of the association between beta-fibrinogen G/A-455 genotype and plasma fibrinogen levels previously observed in healthy men from the UK.

Adult↗
PubMed1993

[Association between fibrinogen and blood sedimentation rate in combined extracorporal and fibrinogen reducing drug therapy].

Fibrinogen appears to play an important role in atherogenesis, whereby high levels of fibrinogen can lead to a disturbance of the haemorheologic pattern. To evaluate the association between fibrinogen and blood sedimentation rate (BSR) 40 patients suffering from cerebral multi-infarct disease underwent a single heparin-induced extracorporeal LDL < fibrinogen > precipitation (HELP). Subsequently they were randomly assigned to two groups, either receiving sustained-release bezafibrate 400 mg daily (n = 21) or placebo (n = 19) over a period of eight weeks. HELP led to a statistically significant reduction of fibrinogen (p < 0.0001). At the end of the trial the difference between the bezafibrate group and the controls became significant (p < 0.05). The BSR strictly followed the course of fibrinogen, indicating a significant reduction after HELP (p < 0.0001 for both BSR values) and a difference between both groups at the end of the study (p < 0.05 and p < 0.03, respectively). The correlation between fibrinogen and BSR remained significant during the whole trial.

Aged↗
PubMed2002

A fibrinogen receptor from group B Streptococcus interacts with fibrinogen by repetitive units with novel ligand binding sites.

Group B Streptococcus (GBS) is a frequent cause of bacterial sepsis and meningitis in neonates. During the course of infection, GBS colonizes and invades a number of host compartments, thereby interacting with different host proteins. In the present report, we describe the isolation of the fbsA gene, which encodes a fibrinogen receptor from GBS. The deduced FbsA protein is characterized by repetitive units, each 16 amino acids in length. Sequencing of the fbsA gene from five different GBS strains revealed significant variation in the number of repeat-encoding units. The deletion of the fbsA gene in the genome of GBS 6313 completely abolished fibrinogen binding, suggesting that FbsA is the major fibrinogen receptor in this strain. Growth of the fbsA deletion mutant in human blood was significantly impaired, indicating that FbsA protects GBS from opsonophagocytosis. In Western blot experiments with truncated FbsA -proteins, the repeat region of FbsA was identified as mediating fibrinogen binding. Using synthetic peptides, even a single repeat unit of FbsA was demonstrated to bind to fibrinogen. Spot membrane analysis and competitive binding experiments with peptides carrying single amino acid substitutions allowed the prediction of a fibrinogen-binding motif with the consensus sequence G-N/S/T-V-L-A/E/M/Q-R-R-X-K/R/W-A/D/E/N/Q-A/F/I/L/V/Y-X-X-K/R-X-X.

Amino Acid Sequence↗
PubMed1982

Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers of rat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. However, if the fragments were incubated with isolated peripheral blood leukocytes, they caused these cells to secrete a factor that when added to the hepatocytes caused an increase in fibrinogen synthesis 4- to 6-fold over controls. Moreover, the hepatocyte-stimulating factor also affected the production of several other proteins produced by the hepatocyte. These results demonstrate that both fragments D and E can stimulate hepatic fibrinogen synthesis via an indirect leukocyte-mediated pathway.

Animals↗
PubMed1983

Fibrinogen Baltimore II: congenital hypodysfibrinogenemia with delayed release of fibrinopeptide B and decreased rate of fibrinogen synthesis.

A congenital hypodysfibrinogenemia, fibrinogen Baltimore II, was found in a young asymptomatic Caucasian female. Prothrombin, partial thromboplastin, and euglobulin lysis times were normal, as were platelet function and coagulation factor assays. Subnormal plasma fibrinogen levels were found using chronometric, rate-independent, and immunologic assay methods. Kinetic analysis of fibrinopeptide release revealed a delay in the thrombin-catalyzed release of fibrinopeptide B from the abnormal protein. Proteolysis of fibrinopeptide A by thrombin or Arvin, fibrin monomer polymerization, and fibrin polymer ligation occurred at normal rates. Catabolism of radiolabeled autologous and homologous fibrinogen was also normal, but the fibrinogen synthetic rate was less than half the normal value. Comparison of the coagulation characteristics of fibrinogen Baltimore II with those of other abnormal fibrinogens indicates that it represents a unique example of hypodysfibrinogenemia.

Adult↗
PubMed1982

Comparative studies on the structures of the carbohydrate moieties of human fibrinogen and abnormal fibrinogen Nagoya.

Human fibrinogen contains four asparagine-linked sugar chains in one molecule. All B beta and gamma subunits obtained from both normal fibrinogen and abnormal fibrinogen Nagoya contain 1 mol each of an asparagine-linked sugar chain. The sugar chains were quantitatively liberated as radioactive oligosaccharides from the polypeptide portion by hydrazinolysis followed by N-acetylation and NaB3H4 reduction. By the combination of sequential exoglycosidase digestion and methylation analysis, the structures of the sugar chains of human fibrinogen were elucidated to be NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNac beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc and Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4GlcNAc. Neither quantitative nor qualitative differences were found between the sugar chain moieties of normal fibrinogen and fibrinogen Nagoya, indicating that the molecular basis of the abnormality in the latter may reside in its polypeptide moieties.

Asparagine↗
PubMed1988

Substitution of gamma Arg-275 by Cys in an abnormal fibrinogen, "fibrinogen Osaka II". Evidence for a unique solitary cystine structure at the mutation site.

In an abnormal fibrinogen with impaired fibrin monomer polymerization designed as fibrinogen Osaka II, we have identified substitution of Arg by Cys at position 275 of the gamma chain. This Cys is linked to a free cysteine molecule by a disulfide link as evidenced by fast atom bombardment mass spectrometry. This finding was supported by identification of a single cysteine released from isolated abnormal fragment D1 upon reduction. This unique cystine structure at the mutation site has not been reported heretofore in any abnormal protein including fibrinogen. The substitution may well perturb the structure required for fibrin monomer polymerization, specifically that assigned to the carboxyl-terminal D domain of fibrinogen. Indeed, isolated fragment D1 with the Cys substitution failed to inhibit thrombin-mediated clotting of normal fibrinogen and normal fibrin monomer polymerization, while normal fragment D1 inhibited them markedly. Our data seem to provide supporting evidence that the putative polymerization site(s) assigned to the D domain of fibrinogen may be structure-dependent, including the carboxyl-terminal segment of the gamma chain as well as a contiguous region that contains the gamma 275 residue.

Adolescent↗
PubMed1993

Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin alpha-chain to fibrin polymerization site 'A': effects of fibrinogen and fibrinogen derivatives, and pretreatment of samples with NaSCN.

A novel murine monoclonal antibody against the fibrin alpha-chain N-terminus is presented, which reacts with desAA- and desAABB-fibrin. In immunoblot procedures, the antibody reacted with fibrin degradation products X and Y of non-crosslinked fibrin, and fragment E. No binding was observed to the fibrin fragment D-dimer, and fibrinogen fragments D and E. Minor binding to fibrinogen fragments X, and Y, and desBB-fibrin were presumably due to minor contamination with (desAA)-fibrin. A prerequisite for binding was release of fibrinopeptides A (FpA), the binding site being a fibrin-specific neo-epitope. No binding was observed to fibrinogen or to thrombin-treated dysfibrinogen MANNHEIM III (A alpha 16 Arg-->Cys) molecules, which do not release FpA. The antibody bound to abnormal fibrin molecules prepared from dysfibrinogen MANNHEIM I (A alpha 19 Arg-->Gly), albeit to a lesser extent than to normal fibrin. Binding of the antibody to the fibrin epitope was greatly enhanced by denaturation, e.g. by heat, or by treatment with chaotropic ions. Soluble fibrin in clinical samples is generally found as a complex with fibrinogen, since polymerization sites 'A' exposed by release of FpA react with complementary binding sites 'a' on the D-domains of other fibrin and fibrinogen molecules. Treatment of samples with NaSCN caused dissociation of fibrin monomer complexes. Reassociation was prevented by denaturation of both polymerization sites 'A' and 'a'. The antibody in combination with NaSCN-treatment of samples was useful for specific detection of fibrin monomer in plasma samples. Measurement was not influenced by fibrinogen degradation products, whereas fibrin degradation products at very high concentration caused some underestimation of fibrin monomer concentration.

Animals↗
PubMed1997

Platelet adhesion to fibrinogen, fibrin monomer, and fibrin protofibrils in flowing blood -- the effect of fibrinogen immobilization and fibrin formation.

Platelet fibrin(ogen) adhesive interactions were investigated in whole citrated blood using the rectangular perfusion chamber at wall shear rates of 300 and 1600 s(-1) with regard to the amount and structure of immobilized protein. Only single platelets adhered to adsorbed fibrinogen at both low and high surface fibrinogen concentrations and at 1600 s(-1) almost no adhesion was observed. When using spray-immobilized protein, platelet adhesion was significantly higher than to adsorbed protein. Conversion of adsorbed fibrinogen to fibrin monomer resulted in the formation of pronounced platelets aggregates and with the elevation of wall shear rate 50% decrease of adhesion took place. Degree of platelet adhesion to fibrin monomer was significantly influenced by immobilized protein concentration at both shear rates. However, the morphology (small and dense platelet aggregates) and extent of platelets adhered to fibrin pentamer was nearly the same at both shear rates. Starting with surface-bound fibrinogen and alternating addition of thrombin and fibrinogen fibrin pentamer was prepared using the stepwise synthesis. This methodology is based on the observation that at low concentration immobilized fibrin monomer binds fibrinogen in 1:1 molar ratio. The gradually formed fibrin of a defined size and composition can be a useful tool in the further understanding of the role of fibrin architecture in the pathophysiology of thrombosis.

Adsorption↗
PubMed1988

Molecular and supramolecular structure of adsorbed fibrinogen and adsorption isotherms of fibrinogen at quartz surfaces.

The adsorption of fibrinogen to quartz surfaces was measured by ellipsometry, ELISA, and electron microscopy. The initial adsorption at low concentrations was diffusion rate limited as determined by the ELISA and by counting the number of adsorbed molecules at electron micrographs. From ellipsometry, ELISA, and electron microscopy measurements it was found that the surface concentration of adsorbed fibrinogen increased continuously over four decades in bulk concentration of fibrinogen. At a hydrophilic quartz surface a plateau level of the adsorption isotherm was found at a surface concentration of 0.1 pmol/cm2 where the adsorbed molecules had a mean intermolecular distance of 10 +/- 5 nm between neighbors. At higher surface concentrations the molecules were densely packed and formed a layer where single molecules could not be identified. Adsorbed fibrinogen showed different structure at hydrophobic and hydrophilic quartz surfaces. At a hydrophilic surface, the fibrinogen molecules appeared as a 46 nm nodose rod consisting of 6-7 nodes with a diameter of 4 nm. At a hydrophobic surface, the molecule appeared as a binodular or trinodular rod with a node diameter of 5-9 nm, connected with a thin filament to form a 40-nm rod. Adsorption from higher concentrations of fibrinogen in solution resulted in adsorbed spheric structures with a diameter of 18-24 nm at the hydrophobic surface and in end-to-end polymers at the hydrophilic quartz membrane.

Adsorption↗
PubMed1978

Characterization of the amino acids of bovine fibrinogen involved in the fibrinogen-thrombin interaction of the blood clotting process. Comparison with the milk clotting process.

Bovine fibrinogen and the Aalpha and Bbeta chains of bovine fibrinogen have been subjected to chemical modification by a number of reagents and the effects of these procedures on the susceptibility of the proteins to thrombin hydrolysis is described. The reagents used were rose bengal (for photo-oxidation), 2-hydroxy-5-nitrobenzyl bromide, N-acetylimidazole, iodoacetic acid and diethyl pyrocarbonate. Evidence is presented which indicates that the tryptophan and tyrosine residues of fibrinogen are not involved to any great extent in the interaction of this protein with thrombin. Modification with iodoacetic acid suggests that methionine residues play a major role in such interactions, but the fibrinogen chains on which the important residues reside remain uncertain. The use of diethyl pyrocarbonate indicates the participation also of histidine in fibrinogen-thrombin interactions and that, whereas the histidine residues of the Bbeta chain are involved to a great extent, it appears that those of the Aalpha chain are not. The similarities which exist between the fibrinogen-thrombin and the kappa-casein-chymosin systems are discussed.

Amino Acid Sequence↗
PubMed1977

Fibrinogen Marburg a new genetic variant of fibrinogen.

A new case of congenital dysfibrinogenemia has been discovered in a 20 year old woman, who suffered from a severe postpartal hemorrhage after the delivery of her first child, followed by episodes of thrombosis. Coagulation studies reveal a prolongation of thrombin time, reptilase time was immeasurable. Thromboplastin time and partial thromboplastin time were slightly prolonged. Low fibrinogen levels were obtained by techniques, which depend on the coagulation velocity following addition of thrombin, while immunological procedures gave slightly diminished values of fibrinogen. Patients's fibrinogen had a moderate inhibitory effect on the fibrin formation in normal plasma. However, inhibitors of the fibrinogen-fibrin conversion could not be detected. Coagulation factors were normal, fibriolysis as well. The cause of the coagulation disorder was found to be a defect of the fibrinogen molecule, leading to an abnormal fibrin polmerization of patient's fibrin monomers. The release of the fibrinopeptides in the paperelectrophoresis was normal. The defect of the fibrinogen molecule did not protect from thrombotic complications. The same defect could be found in the lower scale in patient's father, 4 of her 7 brothers and sisters, and her son.

Adult↗
PubMed1992

Increased phosphate content of fibrinogen in vivo correlates with alteration in fibrinogen behaviour.

Fibrinogen was purified from five patients admitted for hip-replacement surgery the day before (day 0), the day after (day 2) and and one week after the operation (day 8). The behaviour of each patient's three fibrinogens was compared in thrombin gelation assays and plasmin degradation experiments to investigate whether the reported increase in protein-bound phosphate at day 2 and day 8 had any effect on the functional behaviour of fibrinogen as has been demonstrated in vitro. It was found that the thickness of the fibrin fibres produced by thrombin increased markedly at day 2 and declined thereafter. Susceptibility to plasmin appeared to decrease post-operatively by 50% and remained at that level on day 8 despite the phosphate content returning to normal. This has also been shown for fibrinogen phosphorylated in vitro. We conclude, after testing the fibrinogens with and without alkaline phosphatase pretreatment, that our data most resemble the published findings for in vitro phosphorylation of fibrinogen by casein kinase II.

Acute-Phase Reaction↗
PubMed2005

Secreted protein acidic and rich in cysteine (SPARC/osteonectin/BM-40) binds to fibrinogen fragments D and E, but not to native fibrinogen.

Secreted protein acidic and rich in cysteine (SPARC/osteonectin/BM-40) is a matricellular protein that functions in wound healing. Fibrinogen is a plasma protein involved in many aspects of wound healing, such as inflammation, fibrosis and thrombosis. In this study, the binding of SPARC to both native and plasmin-cleaved fibrinogen under physiological conditions was examined by the use of a surface plasmon resonance (SPR) biosensor. We show that SPARC binds to plasmin-cleaved fibrinogen, but not to native fibrinogen. SPARC binds to both fibrinogen fragments D and E fg D and fg E with similar dissociation constants (8.67 x 10(-8) M for Fg D and 1.61 x 10(-7) M for Fg E). Results from endothelial cell proliferation assays show that the binding of SPARC to Fg E suppressed the inhibition of proliferation by SPARC, whereas the binding of SPARC to Fg D did not influence the activity of SPARC on the cell cycle. The interaction of SPARC with fibrinogen fragments D and E, which are produced as a result of proteolytic activation of fibrinolysis, reveals potential storage sites in provisional extracellular matrix for SPARC during the wound healing process and indicates a regulatory role of SPARC in fibrinolysis and angiogenesis.

Animals↗
PubMed2006

Fibrinogen Guarenas, an abnormal fibrinogen with an Aalpha-chain truncation due to a nonsense mutation at Aalpha 467 Glu (GAA)-->stop (TAA).

Fibrinogen Guarenas is a dysfibrinogenemia with a nonsense mutation at G4731T that causes an Aalpha-chain truncation at Ser 466. This abnormal fibrinogen is associated with a bleeding diathesis, severe in the proposita and mild in one brother, even though the fibrinogen levels in plasma are normal. All other family members are asymptomatic. Fibrinogens from the proposita and one family member, the mother of the proposita, both heterozygous for the mutation, were studied. Turbidity curves of fibrin polymerization showed that the lateral association of protofibrils was impaired and the maximum rate of polymerization was slightly diminished. The binding of albumin to fibrinogen was increased compared to control due to the presence of a free sulfhydryl group because of the missing disulphide bridge between Aalpha-Cys 442-472 in the mutated molecules. The abnormal fibrinogen formed much less alpha-polymer, and gamma-dimer formation was delayed compared to the control. Plasminogen activation by t-PA in the presence of fibrin was decreased. When Guarenas clots were perfused with fibrinolytic enzymes, clot degradation was retarded. Clot structure studied by confocal 3D microscopy showed that the fibrin network was dense, made up of thin and highly branched fibers, which accounted for the decreased flow rates by buffer permeation and increased rigidity of the fibrin clots, measured using a torsion pendulum. It seems that the increased clot rigidity, decreased porosity, hypofibrinolysis and t-PA induced fibrinolysis, by itself are not necessarily associated with thrombotic disorders in dysfibrinogenemia.

Afibrinogenemia↗