The effect of acetylsalicylic acid on fibrin gel lysis by tissue plasminogen activator

Williams, Stella; Fatah, K.; Ivert, Torbjörn; Blombäck, Margareta

doi:10.1097/00001721-199512000-00004

Cited by 52 publications

(43 citation statements)

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“…These findings are in accordance with the observed resistance to fibrinolysis of cross-linked plasma fibrin with a tight network architecture. 2,4,5 However, opposite results have been reported with purified and non-crosslinked fibrin, depending on the conditions of fibrin formation. 3,6 Unlike clots made of purified fibrinogen with a tight network obtained under high salt conditions, those obtained by adding contrast media before clotting were found to be more resistant to fibrinolysis than coarse purified fibrin obtained without contrast media.…”

Section: Discussionmentioning

confidence: 93%

“…The theory of a decrease of plasminogen binding to fibrin 3 has been strengthened from observations showing that clots with a fine fibrin (tight) conformation display a slower lysis rate than those with a coarse fibrin (loose) conformation. 2,4,5 So far, neither a molecular nor a structural basis has been detected for these differences. Moreover, a recent report demonstrates that under other conditions clots made of thin fibers may be lysed faster.…”

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confidence: 99%

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Influence of Fibrin Network Conformation and Fibrin Fiber Diameter on Fibrinolysis Speed

Collet

Park

Lesty

et al. 2000

ATVB

443

427

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Abstract-Abnormal fibrin architecture is thought to be a determinant factor of hypofibrinolysis. However, because of the lack of structural knowledge of the process of fibrin digestion, relationships between fibrin architecture and hypofibrinolysis remain controversial. To elucidate further structural and dynamic changes occurring during fibrinolysis, cross-linked plasma fibrin was labeled with colloidal gold particles, and fibrinolysis was followed by confocal microscopy. Morphological changes were characterized at fibrin network and fiber levels. The observation of a progressive disaggregation of the fibrin fibers emphasizes that fibrinolysis proceeds by transverse cutting rather than by progressive cleavage uniformly around the fiber. Plasma fibrin clots with a tight fibrin conformation made of thin fibers were dissolved at a slower rate than those with a loose fibrin conformation made of thicker (coarse) fibers, although the overall fibrin content remained constant. Unexpectedly, thin fibers were cleaved at a faster rate than thick ones. A dynamic study of FITC-recombinant tissue plasminogen activator distribution within the fibrin matrix during the course of fibrinolysis showed that the binding front was broader in coarse fibrin clots and moved more rapidly than that of fine plasma fibrin clots. These dynamic and structural approaches to fibrin digestion at the network and the fiber levels reveal aspects of the physical process of clot lysis. Furthermore, these results provide a clear explanation for the hypofibrinolysis related to a defective fibrin architecture as described in venous thromboembolism and in premature coronary artery disease. Key Words: fibrin Ⅲ fibrinolysis Ⅲ confocal microscopy T he fibrin matrix has a much more complicated role than that of providing the scaffolding of the thrombus or being the target of fibrinolysis. Abnormal fibrin structure in vitro has been related to in vivo premature coronary artery disease in young patients and to severe venous thromboembolic disease in patients with dysfibrinogenemias. 1,2 In those situations, an abnormal fibrin matrix made up of abnormally thin fibers has been shown to promote hypofibrinolysis and embolization. Although much is known about the molecular basis of fibrinolysis, relationships between fibrin conformation and fibrinolysis need to be clarified.Fibrin actively regulates its self-dissolution through numerous interactions with fibrinolytic and antifibrinolytic components. Activation of plasminogen by tissue plasminogen activator (tPA) that is initiated on the conversion of fibrinogen into fibrin is a critical step that is affected by fibrin structure. The theory of a decrease of plasminogen binding to fibrin 3 has been strengthened from observations showing that clots with a fine fibrin (tight) conformation display a slower lysis rate than those with a coarse fibrin (loose) conformation. 2,4,5 So far, neither a molecular nor a structural basis has been detected for these differences. Moreover, a recent report demonstrates that under othe...

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Influence of Fibrin Network Conformation and Fibrin Fiber Diameter on Fibrinolysis Speed

Collet

Park

Lesty

et al. 2000

ATVB

443

427

View full text Add to dashboard Cite

show abstract

“…Fibrin clot properties are likely even worse in stroke patients not receiving aspirin that increases clot permeability and facilitates fibrin lysis. 3,9 Alterations in fibrin function/structure in stroke patients with PFO cannot be attributed to the activation of coagulation observed shortly after PFO closure. 11 Higher clot permeability and faster lysis in stroke patients with PFO than in those without PFO is likely explained by lower proportion of smokers in the former group.…”

Section: Discussionmentioning

confidence: 99%

Altered Fibrin Clot Structure/Function in Patients With Cryptogenic Ischemic Stroke

Undas

Podolec²,

Zawilska³

et al. 2009

Stroke

120

110

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Background and Purpose-We tested the hypothesis that fibrin structure/function is unfavorably altered in patients with cryptogenic ischemic stroke. Methods-Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were determined in 89 patients with patent foramen ovale (PFO) and a history of first-ever stroke, 58 patients with first-ever stroke and no PFO, and 120 healthy controls. Results-Stroke patients, evaluated 3 to 19 months after the event, and controls did not differ with regard to age, sex, smoking, and fibrinogen. Stroke patients with or without PFO had lower clot permeability (PϽ0.0001), faster fibrin polymerization (PϽ0.0001), prolonged clot lysis time (PϽ0.0001), higher maximum D-dimer levels released from clots (PϽ0.0001), and maximum rate of D-dimer release (Pϭ0.02) than controls. Time from stroke occurrence showed no association with any clot variables. Scanning electron microscopy of fibrin clots showed increased fiber diameter and density in stroke patients. Clots from stroke patients with PFO were more permeable and showed shorter lysis time compared to those without PFO, and this was related to lower proportion of smokers in the former group. Conclusions-Altered fibrin clot structure and resistance to fibrinolysis are associated with cryptogenic stroke.

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“…Fibrinolysis in the presence of recombinant tissue plasminogen activator (Boerhinger Ingelheim) was evaluated as previously described. 16,18 Briefly, 100-L citrated plasma was diluted with 100 L of the same buffer containing 20-mmol/L calcium chloride, 1 U/mL human thrombin (Sigma) and 14-mol/L recombinant tissue plasminogen activator. Assembly kinetics were monitored by absorbance at 405 nm for 30 minutes in duplicates.…”

Section: Clot Lysis Assaysmentioning

confidence: 99%

Altered Plasma Fibrin Clot Properties Are Associated With In-Stent Thrombosis

Undas

Zalewski

Krochin

et al. 2010

ATVB

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Objectives-We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties. Key Words: angioplasty Ⅲ fibrin Ⅲ fibrinolysis Ⅲ stents Ⅲ thrombosis T here are several factors associated with increased risk of in-stent thrombosis (IST) in epicardial arteries, including the procedure itself (small final lumen dimension due to stent malapposition and/or underexpansion, stent length, placement of multiple stents, dissections), patient (low left ventricular ejection fraction [LVEF], diabetes mellitus, advanced age, stenting in acute coronary syndrome) and lesion characteristics (bifurcation, in-stent restenosis), stent design and premature cessation of antiplatelet drugs. 1-3 Autopsy studies provided evidence that lack of complete endothelialization and persistent fibrin thrombi are a primary substrate underlying IST. 4,5 Thrombin-mediated fibrinogen conversion to fibrin and fibrin monomer cross-linking result in the formation of a fibrin clot. Its structure and function are modulated by several genetic and environmental factors, predominantly those affecting levels and function of fibrinogen. 6 Effective fibrinolysis is essential for removal of intravascular clots that might otherwise be manifest as thrombosis or enhance the development of atherosclerotic plaques. A more tightly packed and less porous fibrin structure reduces transport of proteins involved in fibrinolysis and anticoagulant reactions mediated by antithrombin inside the clot. These alterations might prolong the presence of fibrin in the lumen. 6 Dense clot fiber networks with reduced susceptibility to lysis have been demonstrated in survivors of myocardial infarction (MI), 7 in the acute phase of MI, 8 and in patients with a history of the no-reflow phenomenon, defined as the absence of a complete myocardial perfusion despite successful opening of the infarct-related artery. 9 Several lines of evidence 10,11 indicate that incompletely endothelialized coronary stents predispose to fibrin deposition and persistent thrombi on the stent struts. However, it is not known whether the IST is associated with unfavorably altered fibrin clot properties that might contribute to this complication regardless of platelet reactivity. Therefore, we sought to evaluate plasma fibrin clot structure/function in patients with definite IST. Methods and Results-We

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The effect of acetylsalicylic acid on fibrin gel lysis by tissue plasminogen activator

Cited by 52 publications

References 0 publications

Influence of Fibrin Network Conformation and Fibrin Fiber Diameter on Fibrinolysis Speed

Influence of Fibrin Network Conformation and Fibrin Fiber Diameter on Fibrinolysis Speed

Altered Fibrin Clot Structure/Function in Patients With Cryptogenic Ischemic Stroke

Altered Plasma Fibrin Clot Properties Are Associated With In-Stent Thrombosis

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