Prothrombotic Fibrin Clot Phenotype in Patients with Deep Vein Thrombosis and Pulmonary Embolism: A New Risk Factor for Recurrence

Undas, Anetta

doi:10.1155/2017/8196256

Cited by 36 publications

(29 citation statements)

References 88 publications

(120 reference statements)

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“…Previous studies have linked fibrin structure to fibrinolytic properties. Clots that are structurally denser and stiffer have an increased resistance to fibrinolysis compared with softer clots, and slower degradation rates have been associated with an increased risk of thrombotic events . Not surprisingly, our results show that neonatal fibrin clots formed immediately after CPB without the influence of other therapies had a significantly faster degradation rate compared with all other groups.…”

Section: Discussionmentioning

confidence: 51%

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Nellenbach

Guzzetta

Brown

2018

Journal of Thrombosis and Haemostasis

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To cite this article: Nellenbach K, Guzzetta NA, Brown AC. Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass. J Thromb Haemost 2018; 16: 2159-67. Essentials• The standard of care (SOC) for treating neonatal bleeding is transfusion of adult blood products. • We compared neonatal clots formed with cryoprecipitate (SOC) to two procoagulant therapies. • The current SOC resulted in clots with increased stiffness and decreased fibrinolytic properties. • Procoagulant therapies may be a viable alternative to SOC treatment for neonatal bleeding.Summary. Background: Bleeding is a serious complication of neonates undergoing cardiopulmonary bypass (CPB) and associated with substantial morbidity and mortality. Bleeding is addressed through the transfusion of adult blood products, including platelets and cryoprecipitate. However, significant differences exist between neonatal and adult clotting components, specifically fibrinogen. Our recent ex vivo studies have shown that neonatal fibrinogen does not fully integrate with adult fibrinogen, leading to decreased susceptibility to fibrinolysis. These differences may contribute to ineffective clot formation and/or an increased risk of thrombosis. A need exists to identify more effective and safer methods to promote clotting in neonates. Objectives: Procoagulant agents, such as prothrombin complex concentrates (PCCs) and recombinant activated factor VII (rFVIIa), are being used off-label to treat excessive bleeding in neonates after CPB. Because these agents stimulate endogenous fibrin formation, we hypothesize that their addition to post-CPB neonatal plasma will better recapitulate native clot properties than cryoprecipitate. Methods: We analyze the structural, mechanical and degradation properties of fibrin matrices formed by neonatal plasma collected after CPB in the presence of an activated four-factor (F) PCC (FEIBA), rFVIIa, or cryoprecipitate using confocal microscopy, atomic force microscopy and a fluidics-based degradation assay. Results: The ex vivo addition of FEIBA and rFVIIa to post-CPB neonatal plasma resulted in enhanced clot networks with differences in fibrin alignment, mechanics and degradation properties. Conclusions: Our results suggest that these procoagulant agents could be used as an alternative to the transfusion of adult fibrinogen for the treatment of bleeding after CPB in neonates.

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Section: Discussionmentioning

confidence: 51%

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Nellenbach

Guzzetta

Brown

2018

Journal of Thrombosis and Haemostasis

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“…It should be underscored that with the increase in compact, highly branched networks with thin fibers significantly correlated with cirrhosis severity. Clots composed of thin fibers and small pores have been suggested to be more thrombogenic [42,46,47], but the mechanisms underlying the formation of these prothrombotic fibrin clots have not yet been described. Our in vitro experiments revealed that oxidative stress is a strong determinant of these evident clot structural changes.…”

Section: Discussionmentioning

confidence: 99%

Super-Resolution Microscopy Reveals an Altered Fibrin Network in Cirrhosis: The Key Role of Oxidative Stress in Fibrinogen Structural Modifications

et al. 2020

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Cirrhotic patients show a reduced synthesis of both pro- and anti-coagulant factors. Recent reports indicate that they are characterized by a higher risk of thrombotic rather than hemorrhagic complications, but the mechanisms conferring this risk are not fully elucidated. Oxidative-mediated fibrinogen modifications may explain, at least in part, a prothrombotic profile. The aim of the present pilot study was to investigate the alterations in fibrinogen structure and function in patients with cirrhosis of various severity and to correlate these findings with the mechanisms of thrombus formation. We assessed in plasma specific oxidative stress markers and measured oxidative modifications, functional and structural parameters in purified fibrinogen fractions obtained from cirrhotic patients and control subjects. We enrolled 15 cirrhotic patients (5 patients belonging to each of the three Child–Turcotte–Pugh classes) and 20 age- and sex-matched healthy controls. Plasma redox status, fibrinogen oxidative modifications, thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in cirrhotic patients and were associated to disease severity. Importantly, clot structure obtained by stimulated emission depletion (STED) super-resolution microscopy indicated modifications in fiber diameter and in clot porosity in cirrhotic patients. Fibrin fiber diameter significantly decreased in cirrhotic patients when compared to controls, and this difference became more marked with disease progression. In parallel, fibrin pore size progressively decreased along with disease severity. In cirrhotic patients, fibrinogen clot analysis and oxidative-dependent changes reveal novel structural and functional fibrinogen modifications which may favor thrombotic complications in cirrhosis.

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“…The role of clot structure and function for prognostic markers in venous thromboembolic disorders specifically is described in another review article. 53 Fibrin clot permeability has also been shown to be a good predictor of stroke and bleeding in anticoagulated patients with atrial fibrillation. 54 Patients clots that had lower Ks were at increased risk of stroke or transient ischemic attack and major bleeds.…”

Section: Structural Clot Changes and Thrombotic Outcomesmentioning

confidence: 99%

Clot Structure and Implications for Bleeding and Thrombosis

Mihalko

Brown

2019

Semin Thromb Hemost

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The formation of a fibrin clot matrix plays a critical role in promoting hemostasis and wound healing. Fibrin dynamics can become disadvantageous in the formation of aberrant thrombus development. Structural characteristics of clots, such as fiber diameter, clot density, stiffness, or permeability, can determine overall clot integrity and functional characteristics that have implications on coagulation and fibrinolysis. This review examines known factors that contribute to changes in clot structure and the presence of structural clot changes in various disease states. These insights provide valuable information in forming therapeutic strategies for disease states where alterations in clot structure are observed. Additionally, the implications of structural changes in clot networks on bleeding and thrombus development in terms of disease states and clinical outcomes are also examined in this review.

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Prothrombotic Fibrin Clot Phenotype in Patients with Deep Vein Thrombosis and Pulmonary Embolism: A New Risk Factor for Recurrence

Cited by 36 publications

References 88 publications

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Super-Resolution Microscopy Reveals an Altered Fibrin Network in Cirrhosis: The Key Role of Oxidative Stress in Fibrinogen Structural Modifications

Clot Structure and Implications for Bleeding and Thrombosis

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