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PubMed1986

Determination of soluble fibrin in plasma by a rapid and quantitative spectrophotometric assay.

A rapid, sensitive and quantitative spectrophotometric assay of soluble fibrin in plasma samples has been developed. The method is based on the principle that fibrin stimulates the activation of plasminogen by tissue plasminogen activator (t-PA). A sample containing fibrin is incubated with t-PA, plasminogen and a plasmin-sensitive chromogenic substrate. An increase in absorbance which is dependent on the fibrin concentration in the sample is obtained. In plasma samples an initial lag-phase, due to the presence of alpha 2-antiplasmin is observed. However, the change in A405 per square minute during the later part of the reaction was found to be proportional to the fibrin content and to generate linear standard curve intercepts at the origin. The detection limit of bathroxobin-digested fibrinogen added to plasma was about 5 nmol/L. Recovery experiments at 20 and 75 nmol/L levels in plasma samples from healthy individuals were excellent. The "within-run" variation (CV) was determined as 3.7%. The formation of fibrin after addition of minute amounts of thrombin to plasma could be monitored with the method. Plasma from 8 healthy individuals was found to contain about 9.2 +/- 1.9 nmol/L fibrin. Plasma samples from 46 patients with a suspected haemostatic disturbance had higher levels of soluble fibrin (53 +/- 62 nmol/L). Seven of the 46 samples had concentrations above 150 nmol/L.

Disseminated Intravascular Coagulation↗
PubMed1985

Platelets interact with fibrin only after activation.

Interactions between platelets and fibrin have been visualized by phase contrast, epifluorescence, and scanning electron microscope examination of clots formed with dansylcadaverine-labeled fibrin and gel-filtered platelets. After thrombin activation, the platelets appeared as fluorescent aggregates with bridging strands of fibrin; formaldehyde-fixed platelets were not fluorescent under the same experimental conditions. Scanning electron micrographs demonstrated that thrombin-activated cells had numerous pseudopods to which the fibrin strands adhered; fixed platelets exhibited a smooth discoid appearance and did not interact with the clot. Platelets trapped in clots formed with Batroxobin (Pentapharm) (platelets are not activated by Batroxobin as confirmed by light-scattering aggregometry measurements) remained as nonfluorescent, discoid cells, whereas platelets first activated by adenosine diphosphate formed brightly fluorescent aggregates. Light-scattering data of thrombin activation (0.2 U/mL) indicated that preincubation of platelets with 0.1 mmol/L prostaglandin E1 (PGE1) prior to addition of thrombin decreased the extent and rate of platelet shape change and resulted in 100-fold slower aggregation. Clots formed in the presence of PGE1 revealed decreased fluorescence intensity and fewer platelet-fibrin contacts. Gly-Pro-Arg-Pro, which blocks fibrinogen binding and fibrin assembly, was also effective in blocking platelet-fibrin interactions. These results indicate that platelet activation is a prerequisite for attachment of platelets to fibrin.

Adenosine Diphosphate↗
PubMed1995

Platelet accumulation on fibrin-coated polyethylene: role of platelet activation and factor XIII.

Platelet accumulation on small- and medium-calibre vascular grafts plays a significant role in graft occlusion. We examined platelet accumulation on the surface of fibrin-coated polyethylene tubing (internal diameter 0.17 cm) during 10 min flow (10 ml/min) at high wall shear rate (764 s-1). Washed platelets labelled with 51Cr were resuspended in Tyrode solution containing albumin, apyrase and red blood cells (hematocrit 40%). When the thrombin that was used to form the fibrin-coated surface was inactivated with FPRCH2Cl before perfusion of the tubes with the platelet: red blood cell suspension, the accumulation of platelets was 59,840 +/- 27,960 platelets per mm2, whereas accumulation on fibrin with residual active thrombin was 316,750 +/- 32,560 platelets per mm2 (n = 4). When the fibrin on the surface was cross-linked by including recombinant factor XIII (rFXIII) in the fibrinogen solution used to prepare the fibrin-coated surface, platelet accumulation, after thrombin neutralization, was reduced by the cross-linking from 46,974 +/- 9702 to 36,818 +/- 7964 platelets per mm2 (n = 12, p < 0.01). Platelet accumulation on tubes coated with D-dimer was ten times less than on tubes coated with D-domain; this finding also supports the observation that cross-linking of fibrin with the formation gamma-gamma dimers reduces platelet accumulation on the fibrin-coated surface. Thrombin-activated platelets themselves were shown to cross-link fibrin when they had adhered to it during perfusion, or in a static system in which thrombin was used to form clots from FXIII-free fibrinogen in the presence of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor XIII↗
PubMed1993

Binding of urinary protein C inhibitor to fibrin(ogen) and its binding mechanism.

The region and mechanism of urinary protein C inhibitor (PCI) binding to fibrin(ogen) were examined using fibrin(ogen)-Sepharose and ligand blotting. Urinary PCI bound to fibrin(ogen)-Sepharose in a heparin-dependent manner at a level about 1.6-fold higher to fibrin-Sepharose than to fibrinogen-Sepharose. Scatchard analysis of the binding between urinary PCI and fibrin(ogen)-Sepharose showed that the Kd for fibrin-Sepharose and fibrinogen-Sepharose were 4.0 nM and 5.7 nM respectively. Ligand blotting using urinary PCI and an enzyme-linked immunoassay showed that urinary PCI bound to fibrinogen, fibrinogen degradation products (X, Y, D and E) and the A alpha-, B beta- and gamma-chains of fibrinogen. Binding between urinary PCI and fibrin(ogen)-Sepharose was slightly suppressed (16%) by alpha-methylmannose and largely suppressed (42%) by EACA, which indicates that the carbohydrate chain and the lysine binding site participate in the binding. These findings suggest that urinary PCI binds to fibrin(ogen) via the A alpha-, B beta- and gamma-chains and its binding is partly mediated by carbohydrate and the lysine binding site.

Aminocaproic Acid↗
PubMed1998

Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant.

OBJECTIVE: To determine whether fibrin sealant can replace suture as a means of holding a cartilage graft securely in the trachea. DESIGN: Randomized blinded control study comparing the use of fibrin sealant vs sutures in laryngotracheal reconstruction in ferrets. We compared results at 7 and 30 days. SUBJECTS: Forty ferrets randomized into 2 groups of 20: fibrin sealant and sutures. Within each group, half were studied at 7 days and the rest at 30 days. No ferrets were withdrawn from study because of adverse effects of the intervention. INTERVENTION: A carved costal cartilage graft was placed in the anterior cricoid split incision, and was secured with either fibrin sealant or sutures. All animals were extubated after recovery from anesthesia. Specimens were examined grossly and histologically. RESULTS: All animals survived until humanely killed. The pathologist, unaware of the groupings, measured lumen expansion in millimeters, cartilage graft migration, mucosal in-growth, degree of inflammation, graft integration, and graft viability. The fibrin sealant group had statistically significant (P<.05) better results in mucosal in-growth. In no categories was the suture group better than the fibrin sealant group. In comparing 7-day with 30-day results, the 30-day group had significantly better results in inflammation and graft viability. CONCLUSIONS: Fibrin sealant can be used in place of sutures with improvement in mucosal growth in costal cartilage laryngotracheal reconstruction in the experimental animal model. Use of fibrin sealant (instead of sutures) may result in less surgical trauma and edema, less surgical time, and faster recovery.

Animals↗
PubMed1986

Antibiotics fail to prevent abscess formation secondary to bacteria trapped in fibrin clots.

We inoculated 120 rats with 2 X 10(9) Escherichia coli or 2 X 10(9) Bacteroides fragilis suspended in normal saline solution or incorporated into fibrin clots. In the control group, all animals died after inoculation with E coli, but none died after the inoculation with B fragilis; both were suspended in normal saline solution. Escherichia coli entrapped in fibrin did not cause mortality but did result in abscess formation in all animals. Bacteroides fragilis incorporated into fibrin clots resulted in abscess formation in the majority of animals. Treatment with gentamicin sulfate, ampicillin sulfate, and cefoxitin sodium completely abolished the mortality secondary to E coli suspended in normal saline solution but did not influence the rate of abscess formation secondary to E coli incorporated into fibrin clots. Similarly, cefoxitin and clindamycin phosphate did not significantly change abscess formation secondary to B fragilis incorporated into fibrin clots. We conclude that systemic antibiotics are ineffective in the prevention of abscesses secondary to bacteria trapped in fibrin, either because they do not reach bactericidal levels in the fibrin clot, as in the case of gentamicin, ampicillin, and clindamycin, or, as in the case of cefoxitin, because of the inoculum effect caused by the high number of bacteria. Fibrinogen or fibrin itself do not afford any protection of bacteria against the action of antibiotics.

Abscess↗
PubMed1996

Effects of fibrin and alpha2-antiplasmin on plasminogen activation by staphylokinase.

Staphylokinase obtains plasminogen activating activity by forming a complex with plasminogen. Although the enzymatic activity of staphylokinase is enhanced by fibrin, how fibrin enhances enzymatic activity has not been determined yet. The effects of fibrin, or fibrinogen fragments, on the activation of plasminogen by staphylokinase was investigated using CNBr-digested fibrinogen fragments (FCB-2 and FCB-5) and plasmin-degraded cross-linked fibrin fragments ((DD)E complex, DD fragments and E fragments). Kinetic analysis of the activity of staphylokinase revealed that its plasminogen activating activity, which was expressed as kcat/Km, was enhanced by FCB-2 (10-fold) and FCB-5 (5-fold). These fibrin fragments caused 38-, 30-, and 8.5-fold increases in activity for the DD fragment, (DD)E complex and E fragment, respectively. Although alpha2-antiplasmin inhibited the activation of plasminogen by staphylokinase, FCB-2 abolished its inhibitory effects, and the plasminogen activating activity of staphylokinase was restored. The inhibitory effects of alpha2-antiplasmin on the activation of mini-plasminogen by staphylokinase were less than for Glu- or Lys-plasminogen, and the inhibitory effect of alpha2-antiplasmin was not altered by fibrin or EACA. These findings indicate that the staphylokinase/plasmin(ogen) complex reacts with fibrin even in the presence of alpha2-antiplasmin, and efficient plasminogen activation takes place on the surface of fibrin.

Aminocaproic Acid↗
PubMed1996

Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels.

The mechanism of neurite penetration of three-dimensional fibrin matrices was investigated by culturing embryonic chick dorsal root ganglia (DRGs) within fibrin gels, upon fibrin gels, and upon laminin. The length of neurites within three-dimensional matrices of fibrin was decreased in a concentration-dependent manner by agents that inhibited plasmin, e.g. aprotinin, or that inhibited plasminogen activation, e.g., epsilon-aminocaproic acid (EACA), or plasminogen antiserum. In contrast, such agents increased the length of neurites growing out from DRGs cultured upon two-dimensional substrates of fibrin and had no effect on the length of neurites growing out from DRGs cultured upon laminin. Visualization of neurites within three-dimensional fibrin matrices demonstrated that the distance between fibrin strands was much smaller than the diameter of neurites. All these data were consistent with the hypothesis that fibrinolysis localized to the region of the neurite tip is an important mechanism for neurite penetration of a physical barrier of fibrin strands arranged in a three-dimensional matrix.

Animals↗
PubMed2006

Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins.

Formation of the epitopes recognized by the rheumatoid arthritis (RA)-specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the alpha- and beta-chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by their amino-acyl environment. Using competition with five citrullinated filaggrin-derived peptides bearing major ACPA epitopes, we confirmed the close cross-reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15-mer peptides derived from all the sites of the alpha- and beta-chains of fibrin harboring arginyl residues were tested by ELISA using ACPA-positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin-derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro-inflammatory effector mechanisms but also via impairment of fibrinolysis.

Amino Acid Sequence↗
PubMed1977

Altered morphology and increased cell adhesiveness of chinese hamster ovary cells cultured on fibrin.

Chinese hamster ovary cells cultivated on fibrin exhibited different characteristic from cells growing on plastic. While sparsely plated cells on plastic dishes had an epithelioid morphology, cells on fibrin assumed a round shape and then converted to a stretched form with protruded processes that increased with cell density. Within a few days, cells fibrinolysed adjacent fibrin and returned to the morphology seen in plastic dishes. When fibrinolysis was inhibited by epsilon-aminocaproic acid (EACA), cells continued to grow on the fibrin for a longer period and showed dense, criss-crossed fibroblast-type congestion. Whereas, cells on plastic maintained pavement-like epitheloid appearance when they grew to a confluent monolayer. The other altered characteristics on fibrin was increased accumulation of cells in multilayers. Normally as Chinese hamster cells on plastic proliferate, many cells float into the medium instead of piling up after they form a monolayer. On the other hand, cells on fibrin, being maintained by the addition of EACA, remained adherent, piling up multilayers instead of floating into the medium. A possible explanation of these findings is that the surface properties of the stretched cells on fibrin are altered to make them more adhesive. A possible link of these characteristics of the cells on fibrin to tumor cell behavior in vivo is dicussed.

Aminocaproates↗
PubMed1990

Platelet-fibrin interaction in the suspension and under flow conditions.

Interactions between platelets and fibrin are important in hemostasis but often confused with platelet-fibrinogen interactions. A stirred mixture of solubilized fibrin and washed platelets at neutral pH range showed drastic reduction in turbidity and concomitant platelet adhesion onto newly formed fibrin strands. This platelet-fibrin interaction did not require platelet activation nor did it cause platelet aggregation. A device consisting of a parallel-plate flow chamber mounted on a fluorescence microscope has been constructed to allow direct visualization and recording of platelet-fibrin interaction under flow conditions. Platelets in whole blood adhered to the fibrin-coated portion but not to the uncoated portion of the flow chamber. Slow motion playback of video tapes indicated that the adhesion phenomenon was a dynamic process that involved attaching, detaching, relocation and transient contact. The fibrin coating influenced platelet adhesion both by increasing the number of cells making short-term attachments to the surface and by increasing the duration of cells attached to the surface. These observations provided basic characteristics of platelet-fibrin interaction.

Blood Platelets↗
PubMed1987

[Characteristics of fibrin formation in stab wounds of the skin, determined by scanning electron microscopy].

In an investigation on fibrin formation in skin cut wounds on guinea pigs using scanning electron microscopy, it was established that immediately after the infliction of cuts on live animals, a fine, netlike fiber structure of fibrin forms that gradually covers the entire wounded surface. In the period early after the cuts blood-forming elements attach to the fibrin net through numerous fine fibrin fibers, which incorporate a great number of thrombocytes. Postmortem investigations of these wounds showed that the fibrin net formed preserves its structure. It was also established that a fibrin net forms over skin wounds that were inflicted at different periods after death. In the wounds in the early periods after death, the fibrin net formed was very similar to the one established on wounds inflicted on living animals. Our investigation describes some peculiar characteristics of the fibrin net formed in living animals; there is a fine fiberlike net and the quantity is definitely larger. These characteristics permit the establishment of whether the wounds occurred before death and how much time has lapsed since then.

Animals↗
PubMed1997

[Cataract surgery in narrow pupil and postoperative fibrin reaction, especially after sphincterectomy].

BACKGROUND: Since increased intraoperative iris irritation can lead to increased postoperative inflammation, we are interested in postoperative reactions to several varied surgical procedures. We performed pupil stretching, iridotomy with iris suture, and partial sphincterectomy. MATERIALS AND METHODS: From January 1995 to January 1996, 100 patients (103 eyes) with narrow pupils underwent cataract surgery. In 13 eyes a iridotomy and iris suture were performed, in 28 eyes a partial sphincterectomy. In 62 eyes there was no surgical intervention after pupil stretching. Postoperative examinations were carried out in the early postoperative phase (up to 5 days postoperative) as well as 4 weeks after surgery. Fibrin reaction was classified according to 3 grades, (1) faint fibrinous threads, (II) fibrinous net, and (III) membranous fibrin exsudation. RESULTS: In the group without additional surgery there was a fibrinous reaction of grade I and II in 11 eyes. This complication occurred after iridotomy and iris suture in four cases and after sphincterectomy in four cases. While the intensity of fibrinous reaction was comparable in the first two groups, the fibrinous reaction after sphincterectomy was more intensive in one eye (grade III). However, response to intensive local antiphlogistic therapy was good. Frequency of fibrinous reaction in the three groups was statistically not significant. It should be pointed out that there was a partial restoration of pupil movements through sphincterectomy: mean pupil diameter was 4 mm, and 2.5 mm under exposure to light. Three patients had no pupillary reaction at all. CONCLUSIONS: Partial sphincterectomy facilities intraoperative manipulations of cataract surgery. Postoperative inflammatory reaction is rare and was very responsive to medical treatment. The reconstruction of pupillary movement is part of full visual function and, last but not least a round pupil is aesthetically more desirable.

Aged↗
PubMed2005

In vivo biological performance of composites combining micro-macroporous biphasic calcium phosphate granules and fibrin sealant.

INTRODUCTION: Fibrin glues are currently used by surgeons and can facilitate the handling of biomaterials. Combining fibrin glue with calcium phosphate bioceramics gives a mouldable composite that cements the granules into the implantation site. In addition to the mechanical aspect of the composite, it has been suggested that the mixture also promotes wound healing. These human blood derivatives contain natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic substances. We compared the bioactivity of two composites combining calcium phosphate granules with two different types of fibrin glue, one with aprotinin and the other with tranexamic acid. MATERIALS AND METHODS: The composite was composed of fibrin glue (Tissucol) and 1 to 2 mm granules of biphasic calcium phosphate granules (MBCP) with a volume ratio of 1 for 2. Bone cavities were drilled in 12 New Zealand rabbits and filled with a composite with aprotinin-fibrin glue on the right condyle and one with tranexamic acid-fibrin glue on the left condyle. The rabbits were randomized into two groups: 3 and 6 weeks of delay. Light microscopy, scanning electron microscopy and image analysis were performed. RESULTS: No adverse reactions were observed in either sample. Bony ingrowth associated with bioceramic resorption by osteoclastic TRAP-positive cells was noted. No significant difference was observed between the two composites. The bony ingrowth and ceramic resorption were qualitatively and quantitatively similar with both composites. CONCLUSION: This study demonstrated that the choice of a natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic agent in the fibrin sealant associated with calcium phosphate granules and used as a bone substitute had no effect on the bioactivity of the composite. It remained efficient in bone reconstruction, no adverse effects were observed, and the bony ingrowth was qualitatively and quantitatively equivalent with the two types of fibrin sealant.

Animals↗
PubMed2006

Open inguinal hernia repair by plug and patch: the value of fibrin sealant fixation.

BACKGROUND: Prosthetic meshes give excellent results in groin hernia repair. However, although recurrence rates are very low, chronic pain remains frequent and mesh fixation may play a role in the occurrence of this complication. The use of fibrin sealant to secure the mesh may represent a useful alternative for the prevention of chronic pain. The aim of this study is to confirm that the mesh may be secured by spraying fibrin sealant and to assess the reduction in the incidence of chronic pain. METHODS: Seventy hernias were operated on in 57 patients and were evaluated on a prospective basis. The procedure involved placement of a plug and patch mesh which was secured with fibrin sealant alone. These patients were compared to a matched retrospective series of 57 patients who underwent the same procedure, except that conventional non-absorbable suture was used to secure the mesh. RESULTS: The two groups were equivalent for inclusion criteria and preoperative data. The complication rate was similar in the two groups. The operative time was shorter in the fibrin sealant group: 7 min for unilateral hernia (p=0.0017) and 16 min for bilateral hernia (p=0.0008). The length of hospital stay was also shorter in the fibrin sealant group (1.8 days vs. 2.5 days: p < 0.0001). There was no recurrence in the fibrin sealant group after a minimum follow-up of 12 months and no recurrence in the suture group after a minimum follow-up of 25 months. Finally, a significant reduction in chronic pain was observed in the fibrin sealant group (3.5% vs. 22.8%: p=0.042). CONCLUSION: This study confirms the effectiveness of fibrin glue in securing prosthetic meshes and reducing chronic inguinal pain.

Adult↗
PubMed2005

Activation of gelatinases by fibrin is PA/plasmin system-dependent in human glomerular endothelial cells.

Evidence suggests that fibrin deposit is related to severity of glomerulonephropathy. Fibrin is considered to play an active role beyond a haemostatic plug or temporary matrix in response to injury. We have reported that fibrin induced specific morphological changes and up-regulated intercellular adhesion molecule-1 expression of glomerular endothelial cells (GECs). Changes of gelatinases activity have been implicated playing a prominent role in glomerular diseases involving matrix turnover. This study examined whether overlying fibrin influences the expression of gelatinase A and B in cultured human GECs and mechanism underlying the activation. No gelatinase activity was detectable in supernatant of cultured GECs; however, physiological concentration of fibrin (0.5-2.0 mg/ml) induced a dramatic expression of activated MMP-2 and MMP-9 at both mRNA and protein level in a dose and time dependent manner. Increased mRNA level of membrane-type 1 matrix metalloproteinases (MT1-MMPs) was also found. Interestingly, we observed that fibrin also induced the expression of tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 by casein zymographic and reverse zymographic analysis. Fibrin plate assay revealed the net activity was PA predominant. Serine protease inhibitor aprotinin blocked the conversion of pro-gelatinase A and B to their active forms. The results demonstrate that overlying fibrin increased the secretion of gelatinase A and B from GECs. PA/plasmin proteolytic pathways contributed to the activation of gelatinases.

Base Sequence↗
PubMed1981

Adsorption to fibrin of native fragments of known primary structure from human plasminogen.

Limited proteolysis of native Glu-plasminogen with pancreatic elastase produced three major fragments, K1+2#3, K4, K5-light chain (miniplasminogen). Fibrin-binding was determined by clotting fibrinogen in the presence of 125I-labelled fragments and measuring 125I in the washed fibrin and in the supernatant. Of the fragments miniplasminogen showed the highest fibrin-binding, the strength of which was intermediate between those of Glu-plasminogen and Lys-plasminogen. The fibrin-binding of all three fragments was decreased by 6-aminohexanoic acid or tranexamic acid. This decrease was most pronounced with K1+2+3. The fibrin-binding of K1+2+3, but not that of K4 and miniplasminogen was decreased by alpha 2-antiplasmin. The fibrin-binding of K1+2+3 and mini-plasminogen was lower in a plasma clot than in a purified fibrin clot. Our results indicate that each of the three fragments can bind to fibrin. They confirm that an alpha 2-antiplasmin-binding site is located on K1+2+3. Furthermore two of the fragments, namely K4 and K1+2+3 contain lysine-binding site(s).

Binding Sites↗
PubMed1994

Overview on fibrinolysis: plasminogen activation pathways on fibrin and cell surfaces.

Plasminogen activation at the surface of fibrin or of cell membranes is a sophisticated specialized system for localized extracellular proteolysis implicated in a large variety of biological functions (fibrinolysis, cell migration and extracellular matrix degradation). Assembly of plasminogen and/or activators at specific binding sites induces conformational changes that make accessible the scissile peptide bond of plasminogen and exposes the active centre of the tissue-type plasminogen activator. The mechanism of activation by pro-urokinase, a second type of activator that binds to cell membrane but not to fibrin, is far from being understood. It may be able, however, in contrast to urokinase, to specifically activate plasminogen bound to partially degraded fibrin. An extremely low Km and high catalytic rate are characteristic of the process of activation at surfaces. In contrast, activation in liquid phase by tissue-type plasminogen activator proceeds at an extremely low catalytic rate. The initiation and amplification of plasminogen activation depend on specific interactions between the modular constitutive units of these proteins and binding sites present on cell or fibrin surfaces. Thus, the most important mechanism for the acceleration of fibrinolysis and pericellular proteolysis is the unveiling of carboxy-terminal lysine residues on these surfaces, to which plasminogen may bind. Since plasminogen bound to carboxy-terminal lysines of progressively degraded fibrin or membranes is readily transformed into plasmin by fibrin-bound t-PA, this mechanism represents the most important pathway for the acceleration and amplification of fibrinolysis. Alpha-2-antiplasmin, by inhibiting plasmin release from surfaces, regulates the extent and rate of this process but has no effect on fibrin-bound or membrane-bound plasmin. Lipoprotein(a), a particle possessing a plasminogen-like apolipoprotein, apo(a), may interfere with this mechanism by inhibiting the specific binding of plasminogen to lysine residues in membrane or fibrin surfaces.

Amino Acid Sequence↗