High functional levels of thrombin-activatable fibrinolysis inhibitor are associated with an increased risk of first ischemic stroke

2005 ◽  
Vol 3 (10) ◽  
pp. 2211-2218 ◽  
Author(s):  
F. W. G. LEEBEEK ◽  
M. P. J. GOOR ◽  
A. H. C. GUIMARAES ◽  
G.-J. BROUWERS ◽  
M. P. M. MAAT ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor

Changes in Activated Thrombin-Activatable Fibrinolysis Inhibitor Levels Following Thrombolytic Therapy in Ischemic Stroke Patients Correlate with Clinical Outcome

2016 ◽  
Vol 42 (5-6) ◽  
pp. 404-414 ◽  
Author(s):  
Marie-Christine Alessi ◽  
Christophe Gaudin ◽  
Philippe Grosjean ◽  
Valérie Martin ◽  
Serge Timsit ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Clinical Severity ◽  
Tissue Type ◽  
Stroke Severity ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Nihss Score ◽  
Multicenter Observational Study ◽  
Fibrinolysis Inhibitor ◽  
Prospective Longitudinal

Background and Purpose: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA). Methods: In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0-1) and unfavorable (2-6) outcomes. Results: A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003). Conclusion: These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment.

The C1542G and G505A Polymorphisms of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in Patients with Thrombotic Microangiopathies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2141-2141
Author(s):  
Christoph Sucker ◽  
Firuseh Farokhzad ◽  
Fieras Dahhan ◽  
Michael Schmitz ◽  
Gerd R. Hetzel ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Arterial Thrombosis ◽  
Case Control ◽  
Thrombotic Microangiopathies ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor ◽  
Inflammatory Processes ◽  
History Of

Abstract Background Thrombotic microangiopathies are characterized by vascular microthromboses, microangiopathic hemolytic anemia, and thrombocytopenia. Although recent research has elucidated the pathogenesis of these rare thrombotic disorders to some extent, the determinants contributing to the onset and modulating the severity are largely unknown. It is likely that risk factors of venous and arterial thrombosis also play a role in this clinical setting. Patients and Methods In the present study, we used a case-control and a case-only design, enrolling 23 patients (mean age [± SD] 35 ± 11 years) with a history of thrombotic microangiopathy and 689 control subjects to assess the role of gene polymorphisms of the thrombin-activatable fibrinolysis inhibitor (TAFI). Results The prevalence of the TAFI decreasing G/G genotype of the C1542G polymorphism was significantly higher in patients compared to controls (odds ratio 3.88; 95 % CI 1.07 – 11.47; p=0.02). In addition, in a case-only design the TAFI 1542 G allele was more prevalent in patients suffering from a severe course compared to those with a mild or moderate course (odds ratio 20; 95 % CI 1.85 – 216.17; p=0.009). By contrast, no such association was found for the TAFI G505A polymorphism. Conclusions Our study shows an association of the TAFI decreasing 1542 G/G genotype with an increased risk for thrombotic microangiopathies and a more severe course. This finding might be explained by the role of TAFI as an inhibitor of local inflammatory processes.

scholarly journals Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Deficient Mice Are Susceptible to Intracerebral Thrombosis and Ischemic Stroke

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11658 ◽  
Author(s):  
Peter Kraft ◽  
Tobias Schwarz ◽  
Joost C. M. Meijers ◽  
Guido Stoll ◽  
Christoph Kleinschnitz
Keyword(s):  
Ischemic Stroke ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Fibrinolysis Inhibitor ◽  
Deficient Mice

scholarly journals High thrombin activatable fibrinolysis inhibitor levels are associated with an increased risk of premature peripheral arterial disease

2011 ◽  
Vol 127 (3) ◽  
pp. 254-258 ◽  
Author(s):  
Emile L.E. de Bruijne ◽  
Ann Gils ◽  
Dingeman C. Rijken ◽  
Moniek P.M. de Maat ◽  
Ana H.C. Guimarães ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor ◽  
Peripheral Arterial

Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels

2008 ◽  
Vol 100 (07) ◽  
pp. 38-44 ◽  
Author(s):  
Michiel Coppens ◽  
Nic J. G. M. veeger ◽  
Victor J. J. Bom ◽  
Saskia Middeldorp ◽  
Karly Hamulyak ◽  
...  
Keyword(s):  
Factor Viii ◽  
Arterial Thrombosis ◽  
Absolute Risk ◽  
Protein S ◽  
Adjusted Relative Risk ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Arterial Thromboembolism ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor ◽  
Prothrombin 20210A

SummaryHigh levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5–1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9–2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.

Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis

2003 ◽  
Vol 90 (12) ◽  
pp. 1187-1191 ◽  
Author(s):  
Robert Hegele ◽  
John Sparkes ◽  
Jerome M.Teitel ◽  
Robert Chisholm ◽  
Herbert Lau ◽  
...  
Keyword(s):  
Plasma Levels ◽  
De Novo ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Native Coronary Artery ◽  
Angiographic Restenosis ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor ◽  
The Relationship ◽  
Pai 1

SummaryThe fibrinolytic system is closely related to several processes that are involved in restenosis. We previously showed that low PAI-1 plasma levels predicted restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been described. The aims of this study were to evaluate the relationship between pre-procedural plasma levels of TAFI and late angiographic restenosis and the interaction between TAFI and PAI-1. We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty or stenting of de novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured in plasma samples drawn before the procedure. Follow-up coronary angiography was performed in 92% of patients. There was a significant correlation between pre-procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p = 0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural TAFI levels were significantly higher in patients with restenosis (108 ± 33% versus 94±30%, p = 0.011). Restenosis rates for patients in the upper tertile of TAFI levels were 2-fold higher than for those in the lowest tertile (45% versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels identified patients at the highest risk of restenosis (53%) compared to 14% in patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre-procedural plasma TAFI antigen levels identify patients at increased risk for restenosis after PCI.

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