Fibrin in human plasma: Gel architectures governed by rate and nature of fibrinogen activation

Blombäck, Birger; Carlsson, Kjell; Fatah, K.; Hessel, Birgit; Procyk, Roman

doi:10.1016/0049-3848(94)90227-5

Cited by 241 publications

(200 citation statements)

References 30 publications

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“…5,8,10,[16][17][18][19][20][21] In particular, the thrombin concentration influences both the fiber thickness and density of the fibrin clot. Low thrombin concentrations produce very turbid, highly permeable fibrin clots that are composed of thick, loosely-woven fibrin strands (Figure 1).…”

Section: Nih Public Accessmentioning

confidence: 99%

Thrombin generation, fibrin clot formation and hemostasis

Wolberg

Campbell

2008

Transfusion and Apheresis Science

298

222

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Hemostatic clot formation entails thrombin-mediated cleavage of fibrinogen to fibrin. Previous in vitro studies have shown that the thrombin concentration present during clot formation dictates the ultimate fibrin structure. In most prior studies of fibrin structure, clotting was initiated by adding thrombin to a solution of fibrinogen; however, clot formation in vivo occurs in an environment in which the concentration of free thrombin changes over the reaction course. These changes depend on local cellular properties and available concentrations of pro-and anti-coagulants. Recent studies suggest that abnormal thrombin generation patterns produce abnormally structured clots associated with an increased risk of bleeding or thrombosis. Further studies of fibrin formation during in situ thrombin generation are needed to understand fibrin clot formation in vivo. Keywordsthrombin; fibrinogen; fibrin; plasmin; fibrinolysis; clot structure; hemophilia; thrombosis Fibrinogen and fibrin clot formationFibrinogen is a 450 Å, 340 kDa trinodular protein present at high (2 -4 mg/mL) concentrations in plasma. Fibrinogen consists of pairs of three different disulfide-linked polypeptide chains: Aα, Bβ, and γ. These six polypeptide chains are arranged with their N-termini converged in a central "E" domain of the molecule. The C-termini of the Bβ and γ chains extend outward into distal "D" domains. The C-termini of the Aα chains are globular and situated near the central E domain of fibrinogen where they interact intra-molecularly. 1 Comprehensive reviews on the biochemistry of fibrinogen and fibrin structure have been published. 2-4Mechanisms of fibrin production have been elucidated in studies conducted by adding exogenous thrombin to purified fibrinogen. These studies have shown that thrombin removes N-terminal peptides from the fibrinogen Aαl and Bβ chains, causing the spontaneous formation of half-staggered, double-stranded protofibrils followed by thickening of protofibril chains. 5 Initial formation of protofibrils occurs during a "lag" phase in which no turbidity increase is detected. Subsequent lateral aggregation of fibrin protofibrils causes a turbidity increase. The magnitude of the turbidity increase relates to the structure of the formed clot; formation of thicker fibers causes a greater increase in final turbidity. 6,7 Fibrin formation can be followed Address correspondence to: Alisa Wolberg, Ph. D., Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 815 Brinkhous-Bullitt Building, CB #7525, Chapel Hill, NC 27599-7525, phone: (919) 966-8430, fax: (919) 966-6718, email: alisa_wolberg@med.unc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production p...

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Section: Nih Public Accessmentioning

confidence: 99%

Thrombin generation, fibrin clot formation and hemostasis

Wolberg

Campbell

2008

Transfusion and Apheresis Science

298

222

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“…and less permeable fibrin network, while a decreased fiber mass-length ratio (m) indicates a reduced fiber diameter [18,19]. The properties of fibrin gel structure depend on the conditions prevailing during activation and the structure may vary between two extremes, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The properties of fibrin gel structure depend on the conditions prevailing during activation and the structure may vary between two extremes, i.e. thin fiber strands with small liquid pores and thicker strands with large liquid pores [9,[18][19][20][21]. The properties of the fibrin network appear to influence the rate of fibrinolysis, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…the permeability coefficient (Ks) and the fiber mass-length ratio (m), was determined as described in Blombäck et al [18]. The plasma samples were dialyzed against TNE-buffer (0.05 mol L À1 Tris, 0.1 mol L À1 NaCl, 1 mmol L À1 EDTA-buffer, with aprotinin 5 kIU mL À1 , pH 7.4) and 1 mL of the dialyzed plasma was then recalcified with CACl 2 to give a final concentration of 20 mmol L À1 in the cuvettes.…”

Section: Blood Chemistry Analysesmentioning

confidence: 99%

“…CSII was administered via an insulin infusion pump. The average age of the patients was 37 (30-45) years and diabetes duration 22 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) years. Twenty-two patients had microangiopathy (retinopathy, microalbuminuria, and/or neuropathy), seven patients were smokers and six were non-smokers for >5 years.…”

Section: Introductionmentioning

confidence: 99%

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Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusion

Jörneskog

et al. 2003

Journal of Thrombosis and Haemostasis

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Summary. Background: Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). Objectives: The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. Patients and methods: Twenty-eight patients were investigated before and after 4-6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. Pfibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. Results: Eighteen patients showed improved and 10 patients unchanged HbA 1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass-length ratio (m) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA 1c (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r ¼ 0.50; P < 0.01) and in LDLcholesterol (r ¼ 0.46; P < 0.05). Conclusions: Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity.

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Haemophilia A and Haemophilia B

Roberts¹

2007

Haemophilia and Haemostasis

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Fibrin in human plasma: Gel architectures governed by rate and nature of fibrinogen activation

Cited by 241 publications

References 30 publications

Thrombin generation, fibrin clot formation and hemostasis

Thrombin generation, fibrin clot formation and hemostasis

Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusion

Haemophilia A and Haemophilia B

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