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Sex-specific alteration to α2-antiplasmin incorporation in patients with type 2 diabetes

Published on Jan 1, 2020in Thrombosis Research3.266
· DOI :10.1016/j.thromres.2019.09.032
Agata Hanna Bryk3
Estimated H-index: 3
(Jagiellonian University Medical College),
Jakub Siudut5
Estimated H-index: 5
(Jagiellonian University Medical College)
+ 4 AuthorsAnetta Undas41
Estimated H-index: 41
(Jagiellonian University Medical College)
Abstract
Abstract Background Type 2 diabetes mellitus (T2DM) is associated with hypofibrinolysis and increased factor XIII-mediated α2-antiplasmin incorporation into the fibrin clot. It is unclear whether there are sex-related differences in α2-antiplasmin incorporation in relation to impaired clot lysis in T2DM. Aim We investigated α2-antiplasmin incorporation into fibrin clots as a determinant of clot lysability in patients of both sexes with T2DM. Methods In a group of 113 T2DM patients, 54 (47.8%) of which were women, we investigated α2-antiplasmin incorporation using an in-house sandwich enzyme-linked immunoassay and plasma clot lysis by turbidimetry, along with fibrinogen and thrombin generation using calibrated automated thrombogram and factor XIII activity. Results Female patients had 15.2% greater α2-antiplasmin incorporation into the fibrin clot with (p = 0.008) and slightly higher plasma α2-antiplasmin concentration (p = 0.005) along with 8.4% longer time to 50% lysis (Lys50MA, p = 0.012) compared with men. Female patients had enhanced thrombin generation represented by shorter lag phase (p = 0.042), shorter time to peak (p = 0.033), and higher endogenous thrombin potential (p = 0.003) compared with men, while factor XIII activity was comparable between sexes (p = 0.085). On multivariate regression, patient sex and glycated hemoglobin (HbA1c) level were the predictors of α2-antiplasmin incorporation in the entire patient group, while α2-antiplasmin incorporation was associated with Lys50MA, as were fibrinogen, male sex and body-mass index. Conclusions This study suggests that a more compromised fibrinolysis in diabetic women when compared with men could be in part mediated by increased α2-antiplasmin incorporation into the fibrin.
  • References (34)
  • Citations (1)
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References34
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#2Andrea Csapó (University of Debrecen)H-Index: 1
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Abstract The ever-increasing research efforts to develop new antithrombotic therapies have led to the reassessment of the role of alpha-2-plasmin inhibitor (α2-PI) in pathological conditions. In particular, experimental stroke studies have suggested correlation between increased free α2-PI level and mortality. However there are only a small number of well-characterized and specific assays available for the measurements of free α2-PI. In plasma α2-PI undergoes both N- and/or C-terminal cleavages ...
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#1Agata Hanna Bryk (Jagiellonian University Medical College)H-Index: 3
#2Shannon M. Prior (UVM: University of Vermont)H-Index: 3
Last. Anetta Undas (Jan Kochanowski University)H-Index: 41
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Background Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM.
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#1Shirley Uitte de Willige (Erasmus University Medical Center)H-Index: 4
#2Joyce J.C.M. Malfliet (Erasmus University Medical Center)H-Index: 1
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Aims: To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS). Methods and results: Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death,...
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textabstractEssentials Factor XIIIa inhibits fibrinolysis by forming fibrin-fibrin and fibrin-inhibitor cross-links. Conflicting studies about magnitude and mechanisms of inhibition have been reported. Factor XIIIa most strongly inhibits lysis of mechanically compacted or retracted plasma clots. Cross-links of α2-antiplasmin to fibrin prevent the inhibitor from being expelled from the clot. Summary: Background Although insights into the underlying mechanisms of the effect of factor XIII on fibri...
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