Altered properties of the fibrin gel structure in patients with IDDM

Jörneskog, Gun; Egberg, Nils; Fagrell, B; Fatah, K.; Hessel, Birgit; Johnsson, Hans; Brismar, Kerstin; Blombäck, Margareta

doi:10.1007/s001250050607

Cited by 95 publications

(80 citation statements)

References 22 publications

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“…Although previous groups have demonstrated changes in clot structure to occur in association with type 1 diabetes [17,18], these studies were performed on clots formed from plasma, so it cannot be ruled out that other constitutive plasma proteins (such as albumin and fibronectin [30,31]) and other plasma constituents (the levels or structures of which may become altered in association with the metabolic changes that occur in diabetes) played a role Results are expressed as the mean value for each group with the SEM in parentheses in causing the changes in clot structure found in those studies. By using fibrinogen purified from diabetic and control subjects, we were able to assess the effect of posttranslational modifications of fibrinogen that occur in vivo in association with type 2 diabetes, while eliminating the potential impact of other proteins/plasma constituents, which would confound the results had a plasma system been used.…”

Section: Discussionmentioning

confidence: 94%

“…However, the mechanism(s) by which fibrin clot structure is altered in type 1 diabetes are unclear. The changes found were inversely correlated to glycaemic control (HbA 1 c) [17], leading the authors to suggest that this effect may result from glycation of the fibrinogen molecule. Indeed, fibrinogen has been shown to be glycated in vivo [20], and in vitro glycation of fibrinogen has been shown to influence its interaction with other coagulation/fibrinolytic proteins [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of the structure of the fibrin clot in relation to diabetes has revealed that fibrin clots formed from the plasma of subjects with type 1 diabetes have a denser structure, with smaller intrinsic pores than those formed by healthy control subjects [17,18], a feature that has been shown to enhance a clot's resistance to fibrinolysis [16,19]. However, the mechanism(s) by which fibrin clot structure is altered in type 1 diabetes are unclear.…”

Section: Introductionmentioning

confidence: 99%

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The influence of type 2 diabetes on fibrin structure and function

2005

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Aims/hypothesis: The precise mechanisms underlying the increased risk of cardiovascular disease (CVD) in type 2 diabetes are unclear. Fibrin clot structure has been related to CVD risk in the general population. We therefore assessed this in type 2 diabetic patients as a potential mechanism whereby diabetes influences CVD risk. Methods: Fibrin clots were formed from fibrinogen purified from 150 subjects with type 2 diabetes and varying degrees of glycaemic control (assessed by HbA 1 c), and from 50 matched control subjects. Clot structure was assessed by turbidity, permeation and confocal microscopy. The specific effect of glucose itself was assessed by analysing the structure of clots formed from purified fibrinogen in the presence of increasing concentrations of the sugar. Results: Clots formed by fibrinogen purified from type 2 diabetic subjects had a denser, less porous structure than those from control subjects. The structural changes found were related to the individual's glycaemic control; HbA 1 c correlated negatively with permeation coefficient (K s ) values (indicates clot pore size) (r=−0.57, p<0.0001) and positively with maximum absorbance (indicator of fibre size) (r=0.33, p<0.0001), branch point number (r=0.78, p<0.0001) and fibre density (r=0.63, p<0.0001). The ambient glucose level influenced clot structure; hypo-(<5 mmol) and hyperglycaemia (≥10 mmol/l) were both associated with a reduction in K s values and maximum absorbance, and with increased fibre density and branch point number within clots. Conclusions/ interpretation: The structural differences found to occur in type 2 diabetes and in association with hypo-and hyperglycaemia may confer increased resistance to fibrinolysis, and in consequence contribute to the increase in CVD risk in diabetic patients.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The influence of type 2 diabetes on fibrin structure and function

2005

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“…19,20 After MI, fibrin clots have reduced permeability and a lower fiber mass-to-length ratio. 13,21 There are independent associations between permeability and the extent and severity of coronary artery stenosis and also of fibrinolytic activity.…”

Section: Abnormal Clot Architecture and Atherothrombotic Vascular Dismentioning

confidence: 99%

Genetic and Environmental Determinants of Fibrin Structure and Function

Scott

Ariëns

Grant

2004

ATVB

139

129

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Abstract-The formation of a fibrin clot is one of the key events in atherothrombotic vascular disease. The structure of the fibrin clot and the genetic and environmental factors that modify it have effects on its biological function. Alterations in fibrin structure and function have implications for the clinical presentation of vascular disease. This review briefly describes the key features involved in the formation of a fibrin clot, its typical structure, and function. This is followed by a review of the current literature on genetic and environmental influences on fibrin structure/function and the relationship to clinical disease. Key Words: fibrin Ⅲ hemostatis Ⅲ genetic Ⅲ environment Ⅲ atherothrombosis D iseases associated with the development of thrombosis are a major cause of morbidity and mortality in the developed world. Atherothrombotic vascular disorders develop over many decades and involve the interaction of classic atherogenic risk factors such as diabetes, hyperlipidemia, and hypertension with abnormalities of the inflammatory and hemostatic systems. Arterial disease develops in a high-pressure, high-flow system, with lipid deposition and smooth muscle hyperplasia occurring to form an atherosclerotic plaque. 1 Subsequently, the plaque becomes unstable and ruptures exposing a prothrombotic lipid core activating the clotting cascade and leading to the development of a platelet-rich fibrin blood clot and arterial thrombotic occlusion. The extent of this process determines clinical outcome, ranging from no clinically noticeable event to acute coronary artery syndromes including myocardial infarction (MI), cerebrovascular and peripheral vascular disease, or sudden death. The Formation of a Fibrin ClotFibrin is the major protein constituent of the blood clot and is formed from fibrinogen, a glycoprotein that circulates largely inactively, in the blood stream. Fibrinogen consists of 6 polypeptide chains (A␣, B␤, ␥) 2 held together by disulphide bonds in a molecule with bilateral symmetry (Figure 1). The molecule consists of 3 main structural regions, 2,3 including a central region (E), which contains fibrinopeptides A and B and the amino acid termini of all 6 polypeptide chains, 2 distal regions (D) connected to the E region by 2 ␣-helical coiled segments and the D regions containing the carboxyl termini of the B␤ and ␥ chains, and those of the A␣ chain, which extend to form relatively flexible ␣C-domains, each ending in a globular domain. 2,3 In situations of tissue injury and inflammation, thrombin is generated after cleavage of prothrombin by the Xase complex. Thrombin subsequently binds to fibrinogen and cleaves the amino termini of the fibrinogen A␣ and B␤ chains at region E. This results in the release of fibrinopeptides A and B from fibrinogen, producing fibrin and initiating fibrin clot formation. Release of fibrinopeptide A by thrombin is fast and exposes a polymerization site on the E region of fibrin. 4,5 This combines with a complementary binding site on the ␥ chain in the D region of an adjac...

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“…In those studies, the permeability coefficient (Ks) and fiber mass-length ratio (m) were decreased. A reduced fibrin gel permeability (Ks) has also been demonstrated in patients with Type 1 diabetes, despite no evidence of macroangiopathy and irrespective of microangiopathy [13]. The exact mechanism behind the altered fibrin gel properties in patients with diabetes is unclear, but metabolic factors might be important and inflammatory mechanisms may also contribute.…”

Section: Introductionmentioning

confidence: 99%

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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Altered properties of the fibrin gel structure in patients with IDDM

Cited by 95 publications

References 22 publications

The influence of type 2 diabetes on fibrin structure and function

The influence of type 2 diabetes on fibrin structure and function

Genetic and Environmental Determinants of Fibrin Structure and Function

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

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