Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FIBRIN”

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 505 records · Page 28Linked to original sources
PubMed1991

[An experimental study on effect of bone morphogenetic protein and fibrin sealant in tendon implantation into bone].

The purpose of this investigation was to raise the strength of bone-tendon junctions. Fibrin sealant system and bone morphogenetic protein (BMP) was utilized for tendon implantations in bones. Histological findings, findings of soft X-ray radiograms and changes of the tensile strength at bone-tendon junctions were investigated with the passage of time after a free tendon was inserted into a bone tunnel in the lateral femoral condyle of rabbits and fixed with a pull-out suture. There were 4 groups, (BMP(-).Fibrin(-) Group, BMP(+).Fibrin(-) Group, BMP(-).Fibrin(+) Group, and BMP(+).Fibrin(+) Group). In the BMP(+).Fibrin(+) Group the tendon was combined with the bone at 3 weeks the earliest of the 4 groups. These findings would indicate that the fibrin sealant introduced many fibroblastic cells and undifferential mesenchymal cells early and accelerated restoration of tissue around the tendon. Moreover, BMP incorporated with the fibrin sealant probably acted on the objective region without obstructing the BMP. The fibrin sealant, and the mixture of BMP and fibrin sealant enabled early tendon union with the bone, but didn't contribute to the early formation of enthesis.

Animals↗
PubMed1990

Effects of cross-linking on clearance of circulating alpha-fibrin monomer and its complexes.

Preceding studies showed that fibrin-monomer of the type lacking only fibrinopeptide A (alpha-fibrin) cleared from the circulation more rapidly than a tighter aggregating form of monomer that lacks both fibrinopeptides A and B (alpha beta-fibrin). The rapid clearance of alpha-fibrin may be related to the high dissociability of the soluble complexes that it forms with fibrinogen in blood. In this study, we use cross-linking by factor XIIIa to suppress dissociation of fibrin complexes and examine the effect of the cross-linking on the circulatory half-life of the fibrin. Incubation of alpha-fibrin-monomer/fibrinogen solutions with factor XIIIa before injection in rabbits increased the circulatory half-life of the fibrin (range, 2 to 16 hours) in proportion to the percentage conversion of monomer to cross-linked dimers and small oligomers. Electrophoretic analyses of plasma samples confirmed that, compared with non-cross-linked monomer, cross-linked dimers and small oligomers were long lived and, further, were not degraded. The inhibition of clearance through cross-linking occurs only under conditions that produce partial cross-linking of the fibrin. An opposite effect occurs when cross-linking is allowed to approach completion, as a result of polymerization of the fibrin into large fibers that disappear almost immediately after injection. Cross-linking elicited in vivo with injected factor XIIIa has an inhibitory effect on clearance of injected monomer similar to the effect produced by partial cross-linking in vitro. It is proposed that the prolonged survival of cross-linked dimers and small oligomers in the circulation provides a partial explanation for the frequent prevalence of cross-linked rather than non-cross-linked complexes in blood of human subjects with vascular disease.

Animals↗
PubMed1991

Evidence for thrombin enhancement of fibrin polymerization that is independent of its catalytic activity.

Inhibition of thrombin proteolysis of fibrinogen with D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK) results in irreversible inactivation of the thrombin catalytic site, but the PPACK-inhibited thrombin, through its exosite, retains its ability to bind to fibrinogen or fibrin. Hirudin inactivates thrombin at the catalytic site and also inhibits thrombin exosite binding to fibrin or fibrinogen. PPACK or hirudin was added to a clotting mixture of fibrinogen and active thrombin (enzyme-to-substrate ratio = 1:400 at ionic strength of 0.14; 1:800 at ionic strength of 0.09) before the onset of gelation. Subsequent fibrin assembly was evaluated by turbidity measurements at 350 nm and by determining the fibrin and fibrinogen content of the clots that ultimately formed. Polymerization rates and the fibrin-fibrinogen content of the clots that formed were greater in the PPACK-inhibited system than in the hirudin-inhibited system, and the effect was amplified at the lower ionic strength. PPACK-thrombin also promoted the polymerization of native or prepared mixtures of fibrin and fibrinogen. The results suggest that in addition to its well-recognized role in the proteolytic conversion of fibrinogen to fibrin, thrombin functions through exosite binding to fibrin as a cofactor in fibrin polymerization by accelerating fibrin clot assembly.

Amino Acid Chloromethyl Ketones↗
PubMed1990

Tissue-type plasminogen activator and its substrate Glu-plasminogen share common binding sites in limited plasmin-digested fibrin.

The enzyme tissue-type plasminogen activator (t-PA) and its substrate Glu-plasminogen can both bind to fibrin. The assembly of these three components results in about a 1000-fold acceleration of the conversion of Glu-plasminogen into plasmin. Fibrin binding of t-PA is mediated both by its finger (F) domain and its kringle-2 domain. Fibrin binding of Glu-plasminogen involves its kringle structures (K1-K5). It has been suggested that particular kringles contain lysine-binding sites and/or aminohexyl-binding sites, exhibiting affinity for specific carboxyl-terminal lysines and intrachain lysines, respectively. We investigated the possibility that t-PA and Glu-plasminogen kringles share common binding sites in fibrin, limitedly digested with plasmin. For that purpose we performed competition experiments, using conditions that exclude plasmin formation, with Glu-plasminogen and either t-PA or two deletion mutants, lacking the F domain (t-PA del.F) or lacking the K2 domain (t-PA del.K2). Our data show that fibrin binding of t-PA, mediated by the F domain, is independent of Glu-plasminogen binding. In contrast, partial inhibition by Glu-plasminogen of t-PA K2 domain-mediated fibrin binding is observed that is dependent on carboxyl-terminal lysines, exposed in fibrin upon limited plasmin digestion. Half-maximal competition of fibrin binding of both t-PA and t-PA del.F is obtained at 3.3 microM Glu-plasminogen. The difference between this value and the apparent dissociation constant of Glu-plasminogen binding to limitedly digested fibrin (12.1 microM) under these conditions is attributed to multiple, simultaneous interactions, each having a separate affinity. It is concluded that t-PA and Glu-plasminogen can bind to the same carboxyl-terminal lysines in limitedly digested fibrin, whereas binding sites composed of intrachain lysines are unique both for the K2 domain of t-PA and the Glu-plasminogen kringles.

Binding Sites↗
PubMed1985

Regulation of plasma factor XIII binding to fibrin in vitro.

The binding of plasma factor XIII to fibrinogen or fibrin that has been chemically or enzymatically induced to polymerize was studied. Factor XIII binding was assayed using a 3H-putrescine incorporation assay and an 125I-plasma factor XIII binding assay. More than 80% of the native and radiolabeled plasma factor XIII was bound to fibrin I formed by reptilase in EDTA, citrate, or heparin anticoagulated plasma. Plasma factor XIII and 125I-factor XIII was bound (89.6% to 92.5%) to fibrin II formed by thrombin in either citrate or EDTA anticoagulated plasma. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 125I-plasma factor XIII bound to fibrin I or fibrin II formed by reptilase or thrombin in the presence of EDTA demonstrated the b2-subunit remained bound to the a-chains or thrombin-cleaved a-chains. In the presence of calcium chloride and thrombin, the b2-subunit dissociated and factor XIIIa was bound. Protamine sulfate caused fibrinogen polymerization in the absence of divalent cations and reduced both plasma factor XIII and immunologic fibrinogen levels. Fibrinogen polymerized by protamine sulfate bound plasma factor XIII and the a2-subunit of 125I-platelet factor XIII. Plasma factor XIII was also bound to sonicated non-cross-linked fibrin II in either normal plasma or afibrinogenemic plasma. Plasma levels of several coagulation proteins were unchanged after the addition of reptilase, protamine sulfate, or sonicated fibrin to plasma. These results demonstrate that a specific binding site for the a2-subunit of plasma factor XIII is present on polymerized fibrinogen, fibrin I, and fibrin II. Furthermore, the presence of divalent cations, thrombin-cleavage of plasma factor XIII, and release of fibrinopeptides A or B are not required for plasma factor XIII binding to polymerized fibrinogen and fibrin.

Antithrombins↗
PubMed1989

The polymerization of fibrin prepared from fibrinogen Haifa (gamma 275Arg----His).

Fibrinogen Haifa is a congenital heterozygous fibrinogen variant (gamma 275 Arg----His) characterized by prolonged thrombin and reptilase times and normal fibrinopeptide (FPA, FPB) release. We compared the polymerization rate (by turbidity measurements at 350 nm) and the ultrastructure of Haifa alpha-, beta-, and alpha, beta-fibrin with that of normal. Haifa alpha, beta-fibrin polymerized less rapidly than did normal and formed a highly branched matrix with a smaller mean fiber diameter; this network closely resembled that of normal alpha, beta-fibrin with EDTA added. In the presence of CaCl2 (1 to 10 mM), Haifa alpha, beta-fibrin polymerized more rapidly than in buffer alone and possessed a matrix structure closely resembling that of normal fibrin. From these observations it appears that the functional defect in Haifa fibrin can be related to the inability of the abnormal molecule to effectively utilize available calcium. The polymerization profile of Haifa alpha-fibrin differed only modestly from that of normal alpha-fibrin, whereas that of Haifa beta-fibrin was markedly impaired. This finding plus similarities in the ultrastructure of Haifa and normal alpha-fibrin specimens suggests that the defective gamma chain structure of Haifa fibrinogen results in greater impairment of the carboxy terminal "b" polymerization domain reacting with the site exposed by cleavage of FPB ("B" site) than it does that of the carboxy terminal "a" domain reacting with the site exposed by cleavage of FPA ("A" site). Whether this effect is due to absolute differences in the degree of impairment of these two types of polymerization sites, or whether proper utilization of the "B" to "b" site is dependent upon participation of the "A" to "a" site remains to be determined.

Calcium↗
PubMed1985

Fibronectin and fibrin gel structure.

Plasma fibronectin is covalently incorporated into alpha-chains of fibrin gels in the presence of Factor XIII activated by thrombin (FXIIIaT) but not by Factor XIII activated by the snake venom enzyme batroxobin (FXIIIaB). FXIIIaB catalyzes introduction of gamma-gamma cross-links in fibrin but cross-linked alpha-chains are not formed. In the presence of FXIIIaT, fibrin gels formed by batroxobin incorporated fibronectin and the alpha-chains are cross-linked indicating that FXIIIaB has a different substrate specificity from FXIIIaT. In the presence of FXIIIaT the incorporation of fibronectin approaches 1 mol/340 kDa unit weight of fibrin. Fibronectin when present in a fibrinogen thrombin mixture containing FXIII does not influence the clotting time of the system nor the release of fibrinopeptides. Incorporation of fibronectin is not appreciable before the gel point. This indicates that the polymerization and gelation of fibrinogen is essentially not perturbed by the presence of fibronectin and that fibrin in the gel matrix rather than the fibrin polymers formed prior to gel point is the preferred structure for fibronectin incorporation. Incorporation of fibronectin into fibrin gels during formation leads to an increase in turbidity and a small decrease in Ks (permeability coefficient). This suggests that the width of the strands in the gel increases as a result of fibronectin incorporation. Fibronectin is also incorporated into preformed gels having completely cross-linked gamma- and alpha-chains perhaps indicating that the sites in fibrin involved in fibronectin incorporation are different from those involved in fibrin cross-linking. FXIIIaT appeared to be adsorbed to fibrin gel matrix in the presence but not in the absence of calcium ions.

Batroxobin↗
PubMed1986

Binding of various thrombin fractions to fibrin and the influence of AT-III on their adsorption.

Human thrombin with high affinity for fibrin was obtained by subjecting purified thrombin to affinity chromatography on Sepharose insolubilized fibrin monomers, after addition of a radioiodinated subsample of thrombin, molar ratio 1:600. As judged by radioprofiling of the electrophoretic distribution of high-affinity thrombin on 10 per cent polyacrylamide gel containing urea/SDS, the preparation consisted of 70 per cent alpha-thrombin, 28 per cent beta-thrombin and only 2 per cent gamma-thrombin. Although alpha-thrombin was bound more strongly to insolubilized fibrin monomers than the other subfractions, complete separation of the individual components could not be achieved. High-affinity thrombin was employed for studies on thrombin adsorption to polymerized fibrin, assuming equal behaviour of labelled and unlabelled thrombin. To avoid passive entrapment of thrombin within the fibrin meshwork at physiological pH, ionic strength and calcium concentration, the optimal fibrinogen concentration was found to be 2.94 umol/l. During such conditions, adsorption of thrombin to polymerized fibrin did not exceed 65 per cent of added thrombin, despite an increasing availability of fibrin-related thrombin binding domains obtained by reducing the thrombin concentration. Adsorption of thrombin to polymerized fibrin increased by 25 per cent when the ionic strength was reduced to 0.05 mol/l. These findings suggest the presence of thrombin subfractions with different affinities for polymerized fibrin. Aggregates of high-affinity thrombin formed during its preparation by affinity chromatography, but were prevented by adding polyethylene glycol (m.w. 6,000, final conc. 6.6 g/l). Such aggregates were not inactivated by AT-III, but could still adsorb to polymerized fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1994

[Sealing effect of fibrin glue spray on protection of cerebrospinal fluid leakage through the dura mata].

Fibrin glue, a biologic adhesive, is made with highly concentrated human fibrinogen and clotting factors. It has become used frequently in neurosurgical procedures, in particular in the closure of the dura mata to prevent cerebrospinal fluid leakage. This report evaluates sealing effects of the fibrin glue on cerebrospinal fluid leakage through the dura. (1) Three manipulations for application of fibrin glue were used; i.e., layer, mixture and spray methods. These methods were compared to estimate their sealing effects on water leakage through a 1.2mm pore in an artificial dura. The burst pressure was significantly higher when the spray method was used than when the other two methods were used. (2) Dural incision was made and then sutured at intervals of 2mm, 3mm, 4mm, 6mm, and 8mm. Fibrin glue was applied by a spray method on the sutured dura. The burst pressure of the fibrin plate was over 80cmH2O on every interval of dural suture. (3) Dural defects 2mm, 4mm, 6mm, and 8mm in diameter were made, and then spray of fibrin glue was used to shield the defects. The fibrin clot spreading to the inner and outer surfaces of the pore defect was plug-shaped. The fibrin plug tolerated water pressure over 200cmH2O, in every size of pore. In conclusion, the optimal method for using fibrin glue on the surface of the dura was a spray method. Fibrin plate/clot made by the spray method sealed the dural tear or pore so well that it sustained a water pressure of over 80cmH2O, which is far higher than normal pressure of the intracranial cerebrospinal fluid.

Cerebrospinal Fluid Rhinorrhea↗
PubMed1995

Fibrin enhances the expression of IL-1 beta by human peripheral blood mononuclear cells. Implications in pulmonary inflammation.

Tissue injury is accompanied by increased vascular permeability and influx of plasma proteins including fibrinogen. Fibrinogen is converted into a fibrin matrix by procoagulants activated at the site of tissue injury and inflammation. This fibrin matrix is thought to participate early in the inflammatory response by providing a temporary protein "scaffold" for inflammatory cell adhesion and migration, and subsequent remodeling of the tissue with permanent extracellular matrix proteins such as collagen. Collagen and fibronectin have been shown to regulate the expression of inflammatory cytokines, but whether fibrin can regulate cytokine expression is not known. We hypothesized that fibrin induces the expression of the proinflammatory cytokine IL-1 beta and sought to explore mechanisms responsible for this induction. In this report, we demonstrate that fibrin stimulates human PBMCs to express IL-1 beta message and protein. We show that induction of IL-1 beta by fibrin is mediated partly by the integrin receptor CD11b/CD18 and modulated by cytoskeletal rearrangement. Fibrin also suppresses production of IL-1 receptor antagonist (IL-1ra) a non-bioactive competitor of IL-1 for IL-1Rs. We propose that injured tissues where the conditions favor coagulation and fibrin accumulation, the interaction between mononuclear cells and the newly formed fibrin matrices may elicit the production of the proinflammatory cytokine IL-1 beta. This proposal is supported by immunohistochemical studies which show the co-distribution of fibrin and IL-1 beta in granulomas in lung sections from patients with the systemic granulomatous disease, sarcoidosis.

CD18 Antigens↗
PubMed1993

Oxidized fibrin stimulates the activation of pro-urokinase and is the preferential substrate of human plasmin.

Activated phagocytes participate in physiological thrombolysis producing non-radical excited oxidants and the important proteases elastase and urokinase. The interaction of oxidized fibrin with the proteases of the fibrinolytic system is therefore physiologically relevant. Here it is shown that human pro-urokinase is activated three- to four-fold faster in the presence of an oxidized solid fibrin matrix. In contrast, oxidized fibrin did not favour the fibrinolytic activity of urokinase or t-PA. Measurement of urokinase antigen showed that urokinase bound slightly to strongly oxidized denatured fibrin, whereas pro-urokinase did not. Plasmin degraded oxidized fibrin more rapidly than non-oxidized fibrin. Thus, singlet molecular oxygen (1O2) converts fibrin to a form that stimulates the activation of plasminogen (bound to oxidized fibrin) by pro-urokinase and that of pro-urokinase by plasmin. The oxidative modification of fibrin by 1O2 is specific. In contrast to oxygen radicals (H2O2 in high concentration) 1O2 does not directly destroy protein chains but favours subsequent fibrinolysis. Thus 1O2 prepares fibrin for its specific degradation.

Enzyme Activation↗
PubMed1993

Spreading of platelets on fibrin is mediated by the amino terminus of the beta chain including peptide beta 15-42.

We have investigated the adhesion and spreading of platelets on polymerized fibrin of varying structure to identify sites that mediate these interactions. Fibrin was prepared with thrombin to remove both fibrinopeptide A (FPA) and fibrinopeptide B (FPB) and with reptilase or Agkistrodon contortrix thrombin-like enzyme (ACTE) to selectively remove FPA or FPB, respectively. Residual fibrin-bound enzymes were inhibited with D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK). Platelet adhesion was independent of fibrinopeptide cleavage and was equal on fibrin prepared with each of the three enzymes. In contrast, FPB cleavage increased spreading as quantitated by fluorescence microscopy of platelets stained for glycoprotein IIb-IIIa. The 24% +/- 4% spreading on reptilase-fibrin was significantly less than the 70% +/- 8% on thrombin-fibrin or 65% +/- 9% on ACTE-fibrin (P < .0005 for both). Protease III from Crotalus atrox venom was used to specifically cleave residues B beta 1-42 from fibrinogen to further investigate the role of the beta chain N-terminus in promoting platelet spreading. After clotting with thrombin, this fibrin derivative lacked beta 15-42 and supported significantly less spreading. A monoclonal antibody (MoAb) reactive with beta 15-21 inhibited spreading on thrombin-fibrin as did peptide beta 15-42, while control MoAbs and peptides had no significant effect. These results indicate that adhesion and spreading of platelets on fibrin are mediated by different interactions, and that spreading can be mediated by FPB cleavage and the amino terminus of the beta chain including residues beta 15-42.

Amino Acid Chloromethyl Ketones↗
PubMed1996

Quantitative comparison of fibrin degradation with plasmin, miniplasmin, neurophil leukocyte elastase and cathepsin G.

The relative contribution of plasmin, miniplasmin, PMN-elastase and cathepsin G to the fibrin-gel dissolution is studied. The global kcat/KM ratios are determined as a measure of the fibrinolytic catalytic efficiency using spectrophotometric kinetic analysis of the competition between fibrin and synthetic peptide substrates for the proteases, turbidimetric assay for fibrin dissolution and gel-filtration of the partially degraded fibrin. When the substrate is fibrin polymerized in the presence of 3 mM Ca2+, the value of this ratio is 4.3 x 10(5) M-1.s-1 for plasmin, 1.9 x 10(5) M-1.s-1 for miniplasmin, 5.0 x 10(4) M-1.s-1 for PMN-elastase and 2.2 x 10(3) M-1.s-1 for cathepsin G. When fibrin is polymerized without addition of Ca2+, the kcat/KM values are increased by a factor of 2.3 for plasmin, 2.0 for miniplasmin and 1.6 for cathepsin G, whereas that of PMN-elastase is unchanged. Progressive cross-linking of fibrin decreases the catalytic action of all studied proteases, but no change in their relative contribution to fibrinolysis is observed. When plasmin inhibitor (at physiological concentration) is also cross-linked to fibrin, the most efficient fibrinolytic enzymes are miniplasmin and PMN-elastase. The effect of 6-aminohexanoate on the formation of fibrin degradation products by plasmin and miniplasmin suggests that the high-affinity lysine binding site in the N-terminal kringle domain of plasmin is involved in the interactions with the native polymerized fibrin, whereas the fifth kringle found in both enzymes participates in binding to newly exposed lysine residues. These results provide a quantitative basis for the evaluation of fibrinolytic efficiency and support the concept of synergistic fibrinolysis.

Amino Acid Sequence↗
PubMed1997

[Use of fibrin glue in the prevention of secondary anastomotic stenosis from repair and reconstruction of the injury of the bile duct].

The secondary anastomotic stenosis is often occured from the repair and reconstructive operation of the injured bile duct. It is difficult to treat and the outcome is serious. In order to prevent this complication, the fibrin glue instead of traditional suturing technique combined with inner support was used. Fifty-four hybrid dogs were divided into 3 groups. Group A received Roux-en-y choledochojejunostomy with fibrin glue; group B received Roux-en-y choledochojejunostomy, with a fibrin glue combined support left permanently in the bile duct and group C received Roux-en-y choledocholejejunostomy with fibrin glue combined a support left temporarily in the bile duct. The amount of collagen in the scar was measured at 3/4, 3, 6, 9, 12 months respectively after operation. The results showed: 1. the mature period of scar was shortened from 12 months to 9 months when fibrin glue instead of suture was used in choledochojejunostomy; 2. the mature period of scar was further shortened from 9 months to 6 months when fibrin glue combined with inner support instead of fibrin glue was used in choledochojejunostomy. The conclusions were as follows: 1. fibrin glue could facilitate the healing of wound by inhibiting the formation of scar and accelerrate the maturation of scar; 2. when the inner support was used with fibrin glue in the operation, the mature period of scar could be further shortened; 3. the mechanism of action of the fibrin glue included minimizing the injury, avoiding foreign-body reaction, modifying organization of hematoma, preventing formation of biliary fistular and enhancing intergration and cross-linkage of collagen.

Anastomosis, Roux-en-Y↗
PubMed1998

Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases.

The efficiency of plasmin, miniplasmin, and neutrophil leukocyte elastase in fibrin digestion is well characterized in static systems. Since in vivo the components of the fibrinolytic system are permanently exposed to flow, we have developed two in vitro models and studied the effect of shear forces on fibrin dissolution with these proteases. Cylindrical nonocclusive fibrin clots are perfused at various flow rates through their preformed axial channel, and dissolution of fibrin is followed by measuring the absorbance of degradation products released into the circulating fluid phase. In one experimental setting, fibrin surface is degraded with enzymes applied in the recirculating fluid phase; in another setting, clots containing gel-embedded proteases are perfused with enzyme-free buffer. As shear rate at fibrin surface is changed from 25 to 500 s(-1), the rate of product release by recirculated enzymes increases 2.8-, 2.9-, and 4-fold for plasmin, miniplasmin, and porcine pancreatic elastase, respectively. Buffer-perfused fibrin containing gel-embedded plasmin or miniplasmin is disintegrated by shear forces at a relatively early stage of dissolution, and this disassembly is related to the formation of fragment Y (150 kDa) and fragment D (100 kDa) fibrin degradation products. Fibrin clots degraded by incorporated polymorphonuclear leukocyte elastase, which yields different degradation products, do not disassemble abruptly, even at the highest shear rate (500 s(-1)). Our results suggest that fibrin surface degradation is accelerated with increasing shear rate and that plasmin or miniplasmin embedded in the clot promotes the release of particular clot remnants into the circulating phase, whereas polymorphonuclear leukocyte elastase does not.

Animals↗
PubMed1999

Possible mechanisms through which dietary pectin influences fibrin network architecture in hypercholesterolaemic subjects.

It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a "prudent" diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial. In a previous study performed in our laboratory, it was shown that dietary pectin influences fibrin network architecture in hypercholesterolaemic men without causing any changes in fibrinogen concentration. To elucidate the possible mechanisms, it was necessary to study the possibility that pectin may itself have indirect effects on fibrin network architecture. Pectin is fermented in the gastrointestinal tract to acetate, propionate, and butyrate. In humans, only acetate reaches the circulation beyond the liver. This investigation primarily examined the possibility that pectin may, through acetate, influence fibrin network architecture in vivo. The effects of pectin and acetate supplementation in hypercholesterolaemic subjects were compared. Furthermore, this study also aimed at describing the possible in vitro effects of acetate on fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each received a pectin (15 g/day) or acetate (6.8 g/day) supplement for 4 weeks. Acetate supplementation did not cause a significant change in plasma fibrinogen levels. As in the pectin group, significant differences were found in the characteristics of fibrin networks developed in plasma after 4 weeks of acetate supplementation. Fibrin networks were more permeable (from 213+/-76 to 307+/-81 x 10(11) cm2), had lower tensile strength (from 23+/-3 to 32+/-9% compaction), and were more lyseable (from 252+/-11 to 130+/-15 minutes). These results strongly suggest that the effect of pectin on network architecture could partially be mediated by acetate. Progressive amounts of acetate were used in vitro to investigate the possibility that acetate may be directly responsible for changes that occurred in fibrin network architecture in the plasma medium. Results indicated that acetate influenced fibrin network architecture directly. From the results, it seems highly possible that acetate may be responsible in part for the beneficial effects of pectin supplementation in vivo. It is evident that pectin or acetate supplementation can be useful during the treatment or prevention of some clinical manifestations, especially those associated with raised total cholesterol and possibly also plasma fibrinogen.

Adult↗
PubMed1991

Fibrin and fibrinogen-related antigens in systemic sclerosis (scleroderma)

Abnormalities in fibrin deposition are implicated in the pathogenesis of vascular occlusion in systemic sclerosis. We have used a technique that involves electrophoresis and densitometric analysis of captured fibrin- and fibrinogen-related antigens to measure the concentration of the individual fibrin and fibrinogen degradation products in 13 patients with systemic sclerosis and in 15 healthy control subjects. As a group, patients with systemic sclerosis had markedly elevated levels of total fibrin-related antigen (p = 0.0007) and D-dimer (p = 0.0004), the terminal degradation product of cross-linked fibrin. The levels of fibrin monomer, an intermediate product in the conversion of fibrinogen to cross-linked fibrin, and of D-monomer, a terminal breakdown fragment of fibrinogen and fibrin monomer, were also elevated (p less than 0.005). We conclude that patients with systemic sclerosis have evidence of enhanced fibrin formation and degradation.

Adult↗
PubMed1996

Immunologic quantification of fibrin deposition in thrombi formed in flowing native human blood.

We describe a new method for quantification of fibrin in thrombi formed in native human blood at venous and arterial shear conditions in a parallel-plate perfusion chamber device. Thrombi consisting of various proportions of fibrin and platelets were digested by plasmin. Fibrin deposition (micrograms/cm2) was calculated from the measured D-dimer levels. Fibrin deposition in thrombi formed on a tissue factor (TF)-rich surface increased with increasing shear rate from 37 micrograms/cm2 at 100/s to 77 micrograms/cm2 at 2600/s (significant at 95%, ANOVA). The plasma levels of thrombin-antithrombin III complexes (TAT) increased in concert. In contrast, fibrin deposition in thrombi formed on collagen fibrils and the corresponding TAT plasma levels were independent of the shear rate and much lower than those elicited by the TF-rich surface (significant at 95%, ANOVA). The intra-individual variation in fibrin deposition was on average 10%, whereas the inter-individual differences were > 500%. Such a large inter-individual difference has not been detected by morphometry which usually is employed in similar studies. The present method is more accurate and less time-consuming than the morphometric approach. The novel method measures fibrin on the surface and in and around the thrombi, thus total deposited fibrin. In contrast, the morphometry approach quantifies surface coverage with fibrin only, thus being semiquantitative at best.

Collagen↗