Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men

Meltzer, Mirjam E.; Doggen, Catharina Jacoba Maria; Groot, Philip G. de; Meijers, Joost C. M.; Rosendaal, Frits R.; Lisman, Ton

doi:10.3324/haematol.2008.002386

Cited by 39 publications

(29 citation statements)

References 37 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The TAFI polymorphism in breast cancer Xu et al 701 The TAFI genotype's reference group was CC and the TAFI allele's reference group was allele C. CI, confidence interval; OR, odds ratio; TAFI, thrombin-activatable fibrinolysis inhibitor. The increase in TAFI in patients is due to acute phase reactant or due to inflammation [31]. Our results have shown significantly high TAFI levels and the high-risk T alleles frequency in patients while the TT genotype of the Thr325Ile polymorphism had lower TAFI Ag level consistent with the former studies [13,20].…”

Section: Discussionsupporting

confidence: 90%

Plasma thrombin-activatable fibrinolysis inhibitor levels and its Thr325Ile polymorphism in breast cancer

Zhang

et al. 2013

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. Thrombin-activatable fibrinolysis inhibitor (TAFI) has an antifibrinolytic effect as it can remove partially degraded fibrin C-terminal lysine residues and reduce plasmin formation. The purpose of this study was to investigate whether blood TAFI levels and TAFI Thr325Ile polymorphism could be a risk marker of breast cancer. The plasma TAFI antigen (Ag) level was determined using ELISA assay in 256 patients with breast cancer and 192 healthy controls. TAFI Thr325Ile (rs1926447) polymorphism was genotyped in both patients and control groups using PCR-restriction fragment length polymorphism (PCR-RFLP) and sequencing. The results showed that TAFI Ag levels were significantly higher in breast cancer patients than those in controls (100.6 ± 15.2 and 82.7 ± 11.2%, P < 0.001). TAFI Ag levels were correlated with metastasis of breast cancer (P < 0.001). The Thr/Ile (CT) and Ile/Ile (TT) genotypes were found more frequently in patients group compared with the control group [odds ratio (OR) 2.106; (95% confidence interval, CI 1.379-3.217); P < 0.001]. The high-risk T alleles frequency was also higher in patients compared with healthy controls [OR 1.718; (95% CI 1.316-2.243); P < 0.001]. The polymorphism was significantly correlated with TAFI Ag levels in either group (P < 0.001). The Ile/Ile (TT) genotype had the lowest TAFI Ag level, whereas the Thr/Thr (CC) had the highest one. In conclusion, the plasma TAFI levels and TAFI Thr325Ile genotypes were associated with breast cancer patients in Chinese Han populations and could be considered as the risk indicators of breast cancer.

show abstract

Section: Discussionsupporting

confidence: 90%

Plasma thrombin-activatable fibrinolysis inhibitor levels and its Thr325Ile polymorphism in breast cancer

Zhang

et al. 2013

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

show abstract

“…There have been previous studies showing increased [29–31] or decreased TAFI levels [32, 33] in CAD patients. There have been, however, few reports evaluating the effect of TAFI on clot lysis time in diabetic subjects that demonstrated no effect [34] or hypofibrinolysis [35].…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes as a modifier of fibrin clot properties in patients with coronary artery disease

Bochenek

Zalewski

Sadowski

et al. 2012

J Thromb Thrombolysis

View full text Add to dashboard Cite

Altered fibrin clot structure has been reported both in patients with coronary artery disease (CAD) and those with type 2 diabetes mellitus (DM2). The aim of the present study was to evaluate plasma fibrin clot permeability and susceptibility to lysis in patients with DM2 and CAD. We studied 132 consecutive CAD patients, including 67 subjects with DM2, scheduled for elective coronary artery bypass grafting surgery. Ex vivo plasma fibrin clot permeability (Ks) and lysis time (t50%) induced by 1 μg/mL recombinant tissue plasminogen activator (tPA), along with plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tPA, von Willebrand factor (vWF), P-selectin, soluble CD40 ligand (sCD40L), were measured. Diabetic and non-diabetic patients did not differ in regard to demographics and remaining cardiovascular risk factors. Concomitant DM2 was associated with higher glucose (+24.3 %, p < 0.001), fibrinogen (+9.0 %, p = 0.037), PAI-1 (+58.7 %, p < 0.001), tPA (+24.0 %, p < 0.001) and P-selectin (+12.2 %, p < 0.001). Compared with the non-diabetic group, the CAD patients with DM2 had lower Ks (-6.1 %, p = 0.02) and prolonged t50% (+5.1 %, p = 0.04). Multiple regression analysis of the whole study group showed that vWF, PAI-1, fibrinogen and DM2 were the independent predictors of t50% (R2 = 0.58, p < 0.001), while only vWF was an independent predictor of Ks (R2 = 0.22, p < 0.001). This study indicates that DM2 is potent enough to unfavorably affect plasma fibrin clot characteristics despite abnormal clot phenotype typically observed in CAD. Of note, platelet and endothelial markers appear to contribute to fibrin clot properties in CAD concomitant with DM2.

show abstract

“…Individual components of the fibrinolytic system, conversely, had inconsistent predictive value [135]. A2AP and TAFI levels were independently associated with MI, but other fibrinolytic components were not significant when adjusting for other cardiovascular risk factors [136,137]. …”

Section: Measuring Global Fibrinolysis In Clinical Practicementioning

confidence: 99%

Fibrinolysis and the control of blood coagulation

2015

View full text Add to dashboard Cite

Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of cofactors, receptors, and inhibitors. Fibrinolytic activity can be generated either on the surface of a fibrin-containing thrombus, or on cells that express profibrinolytic receptors. In a widening spectrum of clinical disorders, acquired and congenital defects in fibrinolysis contribute to disease morbidity, and new assays of global fibrinolysis now have potential predictive value in multiple clinical settings. Here, we summarize the basic elements of the fibrinolytic system, points of interaction with the coagulation pathway, and some recent clinical advances.

show abstract

Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men

Cited by 39 publications

References 37 publications

Plasma thrombin-activatable fibrinolysis inhibitor levels and its Thr325Ile polymorphism in breast cancer

Plasma thrombin-activatable fibrinolysis inhibitor levels and its Thr325Ile polymorphism in breast cancer

Type 2 diabetes as a modifier of fibrin clot properties in patients with coronary artery disease

Fibrinolysis and the control of blood coagulation

Contact Info

Product

Resources

About