Better increase in fibrin gel porosity by low dose than intermediate dose acetylsalicylic acid

Williams, Stella; Fatah, K.; Hjemdahl, Paul; Blombäck, Margareta

doi:10.1053/euhj.1998.1088

Cited by 54 publications

(41 citation statements)

References 28 publications

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“…31 In our study, clots formed in plasma from patients with CAD taking aspirin were less permeable, whereas lysis time was essentially unaffected compared with age-and sex-matched healthy controls with similar fibrinogen concentrations and lipid profiles. This finding suggests that other determinants of CAD-related changes in blood coagulation, such as tHcy, have a major impact on fibrin clot structure that cannot be easily overcome by aspirin administration.…”

Section: Discussionmentioning

confidence: 41%

Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects

Undas

Brožek

Jankowski

et al. 2006

ATVB

112

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Objective-Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a hypothesis that the clot permeability and its resistance to fibrinolysis is associated with plasma total Hcy (tHcy) in human subjects. Methods and Results-We studied healthy men not taking any medication (nϭ76), male patients with advanced coronary artery disease (CAD) taking low-dose aspirin (nϭ33), men with diabetes mellitus diagnosed recently (median hemoglobin A 1c 7.65%; nϭ16), and patients with isolated hypercholesterolemia (Ͼ7.0 mmol/L; nϭ15). We assessed clot permeability and turbidimetric lysis time as the determinants of fibrin clot structure. In a regression model, including age and fibrinogen, plasma tHcy was an independent predictor of clot permeation and fibrinolysis time in healthy subjects (R 2 ϭ0.88, PϽ0.0001 and R 2 ϭ0.54, PϽ0.0001, respectively). In CAD patients, tHcy and fibrinogen were stronger predictors of the permeation coefficient (R 2 ϭ0.84; PϽ0.0001) than was fibrinogen alone (R 2 ϭ0.66; PϽ0.0001), whereas tHcy was the only predictor of lysis time (R 2 ϭ0.69; PϽ0.0001). Elevated tHcy levels observed after methionine load were not associated with any of the fibrin clot properties. In patients with diabetes or hypercholesterolemia, the influence of Hcy on permeation and, to a lesser extent, on the lysis time was obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels resulted in increased clot permeability (Pϭ0.0002) and shorter lysis time (PϽ0.0001). Conclusions-Our results indicate that plasma tHcy predicts clot permeation and susceptibility to fibrinolysis in healthy men and CAD patients. Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy-thiolactone.

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Section: Discussionmentioning

confidence: 41%

Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects

Undas

Brožek

Jankowski

et al. 2006

ATVB

112

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“…In vitro, clots formed from purified fibrinogen show increased fibrin gel porosity when incubated with aspirin, making them relatively less thrombotic [18]. In vivo, aspirin administration to healthy volunteers favourably alters fibrin clot structure-an effect that is more pronounced with lower doses of aspirin [19,20]. Acetylation of fibrinogen is a likely mechanism for the observed in vitro and in vivo changes in clot structure after aspirin treatment [21].…”

Section: Cardiovascular Risk Reduction: Aspirin and Its Mode Of Actionmentioning

confidence: 99%

Aspirin resistance and diabetes mellitus

2008

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“…Patients with severe coronary artery disease have more rigid clot structures and an elevated fiber mass-to-length ratio. 22 It is of note that this is the case despite subjects being treated with aspirin, which has been shown to increase fibrin clot permeability 23,24 and potentially enhance the response to fibrinolysis. The plasma from healthy male first-degree relatives of patients with premature coronary artery disease also form ex vivo fibrin clots with abnormal structure.…”

Section: Abnormal Clot Architecture and Atherothrombotic Vascular Dismentioning

confidence: 99%

Genetic and Environmental Determinants of Fibrin Structure and Function

Scott

Ariëns

Grant

2004

ATVB

138

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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Better increase in fibrin gel porosity by low dose than intermediate dose acetylsalicylic acid

Abstract: Low dose acetylsalicylic acid causes the greatest increase in fibrin gel porosity; this may well be of therapeutic importance.

Cited by 54 publications

References 28 publications

Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects

Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects

Aspirin resistance and diabetes mellitus

Genetic and Environmental Determinants of Fibrin Structure and Function

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