Inhibition of Fibrinolysis by Coagulation Factor XIII

Rijken, D.C.; Willige, Shirley Uitte de

doi:10.1155/2017/1209676

Cited by 42 publications

(33 citation statements)

References 56 publications

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“…However, the action of FXIII may impact fibrin clot lysis as FXIII facilitates the binding of plasmin inhibitor to the fibrin surface. 23 Of note, we observed significantly higher plasmin a Significant difference between current anabolic androgenic steroid abusers (AAS) and controls as well as current and former AAS abusers. b Significant difference between all three groups.…”

Section: Discussionmentioning

confidence: 72%

Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

Sidelmann

Gram

Rasmussen

et al. 2020

Semin Thromb Hemost

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Abuse of anabolic–androgenic steroids (AASs) is suspected to increase the risk of cardiovascular disease (CVD) and cardiovascular mortality in otherwise healthy individuals. AAS abuse may increase the incidence of CVD by altering the hemostatic balance toward a procoagulant state. Studies on the effect of AAS abuse on the fibrinolytic system, however, have either demonstrated a profibrinolytic effect or no effect of AAS abuse, but the overall effect of AAS on fibrinolysis has not been addressed so far. This cross-sectional study investigated the effect of AAS on fibrin clot lysis, fibrin structure, and the hemostatic proteins, potentially affecting these measures in current and former AAS abusers and healthy age-matched controls. The study population consisted of 37 current and 33 former AAS abusers, along with 30 healthy age-matched controls. Fibrin clot lysis, fibrin structure properties, fibrinogen, coagulation factor XIII (FXIII) plasminogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined. Fibrin clot lysis was significantly reduced in participants abusing AAS compared with former abusers and controls (p < 0.001). Plasma fibrinogen, plasminogen, and plasmin inhibitor were significantly increased in current abusers (p < 0.05). No significant differences were observed with respect to measures of fibrin structure properties, PAI-1, and TAFI (p > 0.05). In conclusion, AAS abuse depresses fibrin clot lysis. This effect is not associated with alterations in fibrin structure but is rather caused by increased plasma concentrations of fibrinogen, FXIII, and plasmin inhibitor. These findings suggest that AAS abuse may be associated with increased thrombotic disease.

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Section: Discussionmentioning

confidence: 72%

Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

Sidelmann

Gram

Rasmussen

et al. 2020

Semin Thromb Hemost

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“…Because PAI-1 has high affinity for tPA [33], and tPA possesses endogenous activity even in its single-chain form [23], the amounts of free tPA, which correlate well with plasma tPA activity, are determined by the balance of plasma concentrations of tPA and PAI-1 [4,46]. These values are also inversely correlated with the euglobulin clot lysis time, which measures the tPA-generated • Enhancement of plg activation by retained tissue-type plasminogen activator (tPA) [14,15] • Suppression of plg activation potential by facilitating tPA detachment by plasminogen activator inhibitor type 1 (PAI-1) [14] On platelet surfaces • Enhancement of the activation of the surface bound plg [16,53] • Thrombin-activatable fibrinolysis inhibitor (TAFI)-dependent [16], FXIII-dependent [9] and PAI-1 and FXIII-dependent inhibition of fibrinolysis [17].…”

Section: Plg Activation Potentialmentioning

confidence: 99%

“…The secretory dynamics of tPA from VECs [14,15] and the substantial contribution of the surfaces of VECs [15], platelets [16,17], and fibrin [18,19] in amplifying plg activation and in triggering subsequent fibrinolysis have been also confirmed. These cells are also actively involved in the negative regulation of fibrinolysis, as mediated by other plasma and cellular components (e.g., thrombin-activatable fibrinolysis inhibitor [TAFI] [9,16] and PAI-1 [20]).…”

Section: Introductionmentioning

confidence: 99%

Regulation of plasminogen activation on cell surfaces and fibrin

Urano

Castellino

Suzuki

2018

Journal of Thrombosis and Haemostasis

103

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SummaryThe fibrinolytic system dissolves fibrin and maintains vascular patency. Recent advances in imaging analyses allowed visualization of the spatiotemporal regulatory mechanism of fibrinolysis, as well as its regulation by other plasma hemostasis cofactors. Vascular endothelial cells (VECs) retain tissue‐type plasminogen activator (tPA) after secretion and maintain high plasminogen (plg) activation potential on their surfaces. As in plasma, the serpin, plasminogen activator inhibitor type 1 (PAI‐1), regulates fibrinolytic potential via inhibition of the VEC surface‐bound plg activator, tPA. Once fibrin is formed, plg activation by tPA is initiated and effectively amplified on the surface of fibrin, and fibrin is rapidly degraded. The specific binding of plg and tPA to lytic edges of partly degraded fibrin via newly generated C‐terminal lysine residues, which amplifies fibrin digestion, is a central aspect of this pathophysiological mechanism. Thrombomodulin (TM) plays a role in the attenuation of plg binding on fibrin and the associated fibrinolysis, which is reversed by a carboxypeptidase B inhibitor. This suggests that the plasma procarboxypeptidase B, thrombin‐activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin bound to TM on VECs, is a critical aspect of the regulation of plg activation on VECs and subsequent fibrinolysis. Platelets also contain PAI‐1, TAFI, TM, and the fibrin cross‐linking enzyme, factor (F) XIIIa, and either secrete or expose these agents upon activation in order to regulate fibrinolysis. In this review, the native machinery of plg activation and fibrinolysis, as well as their spatiotemporal regulatory mechanisms, as revealed by imaging analyses, are discussed.

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“…Subsequent phase consists in a fibrin clot formation from fibrinogen, platelets, and also factor XIII when clot reaches maximum firmness [ 4 ]. The final phase of stabilization involves the fibrinolytic system as well as factor XIII activated responsible for cross-linking of fibrin [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Thromboelastometry Identified Alteration of Clot Stabilization and Factor XIII Supplementation Need in a Patient with Decompensated Liver Disease Undergoing Liver Biopsy

Crochemore

Savioli

2018

Case Reports in Gastrointestinal Medicine

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Liver disease has been considered the prototype of hemorrhagic disease. Disorder in any component of coagulation system can lead to hemorrhage. Deficiency of factor XIII may impair clot strength and clot stabilization and can be accessed by thromboelastometry. We report a case of a patient with a rapid evolution of liver disease who underwent a liver biopsy. Thromboelastometry was performed, evidencing impairment of clot stability. This clotting disorder was corrected with factor XIII concentrate after unsuccessful administration of antifibrinolytic drugs and hepatic biopsy was performed without hemorrhagic complications. Case Presentation. We report the case of a previously healthy 38-year-old man, who presented to our emergency department with clinical signs of rapid progression of acute liver failure. The laboratory tests revealed platelets of 142x103/mm3, plasma fibrinogen concentration of 221 mg/dl, increased international nationalized ratio (INR 1.9), total bilirubin of 3.9mg/dl, direct bilirubin of 2.3mg/dl, ALT 751U/l, and AST 540U/l without acute bleeding. A liver biopsy was indicated. Based on the results of the thromboelastometry, Tranexamic Acid was administered to correct hyperfibrinolysis followed by factor XIII concentrate to correct factor XIII deficiency. Thromboelastometry was normal despite conventional coagulation tests were still altered. So, liver biopsy was performed with no signs of bleeding and without need of further transfusion. Conclusion. Thromboelastometry may be considered a useful, feasible, and safe tool to monitor and manage coagulopathy in patients with liver disease, with the potential advantage of helping avoid unnecessary transfusion in such patients.

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Inhibition of Fibrinolysis by Coagulation Factor XIII

Cited by 42 publications

References 56 publications

Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

Regulation of plasminogen activation on cell surfaces and fibrin

Thromboelastometry Identified Alteration of Clot Stabilization and Factor XIII Supplementation Need in a Patient with Decompensated Liver Disease Undergoing Liver Biopsy

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