Assessment of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Plasma Levels in Inflammatory Bowel Diseases

Saibeni, Simone; Bottasso, B.; Spina, Luisa; Bajetta, M.; Danese, Silvio; Gasbarrini, Antonio; Franchis, Roberto de; Vecchi, Maurizio

doi:10.1111/j.1572-0241.2004.30203.x

Cited by 56 publications

(43 citation statements)

References 37 publications

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“…The finding of increased TAFI levels in our cohort is consistent with a previous report by Saibeni et al (16), who initially showed increased plasma levels of TAFI in IBD patients. They speculated that TAFI may play a key role in regulating the crosstalk between coagulation, fibrinolysis and inflammation.…”

Section: Discussionsupporting

confidence: 93%

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Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis

et al. 2016

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Objective Patients with ulcerative colitis (UC) are at an increased risk for thromboembolic events, particularly in patients with extensive and active disease. To date, a few studies have been published on the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in UC. However, there are no reports in the literature investigating the effect of UC treatment on plasma TAFI levels. Methods The plasma TAFI antigen levels were quantitatively determined using ELISA kits for 20 UC patients at activation and remission, along with 17 healthy controls. The association between the TAFI levels and inflammatory markers was assessed to determine UC activation. To predict and determine the activation of UC, the Truelove-Witts index and the endoscopic activation index (EAI) were used for each subject. Results The plasma TAFI levels were higher in UC patients at activation of the disease compared with the remission state and in healthy controls. Spearman's correlation analyses revealed that the WBC (r: 0.586, p< 0.001), hsCRP (r: 0.593, p<0.001) and EAI (r: 0.721, p<0.001) were significantly correlated with the TAFI levels. The overall accuracy of TAFI in determining UC activation was 82.5% with a sensitivity, specificity, NPV and PPV of 80%, 85%, 81% and 84.2%, respectively (cut-off value: 156.2% and AUC: 0.879). Conclusion The present study demonstrates that the TAFI levels are elevated in the active state of UC. The assessment of TAFI levels in patients with UC in conjunction with other markers of inflammation may provide additional information for estimating UC activation and severity.

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Section: Discussionsupporting

confidence: 93%

“…In addition, several reports suggested alterations in the TAFI levels in IBD, in which the degree of intestinal inflammation and changes in the TAFI levels appears to be correlated (15,16). However, the impact of this correlation remains controversial, with challenging results either with an increase or a decrease in the TAFI levels.…”

Section: Discussionmentioning

confidence: 99%

Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis

et al. 2016

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“…Possibly, the low-grade human endotoxemia model was too mild to induce this secondary increase in TAFI concentrations; otherwise, it is possible that the response differs between humans and mice. Of note, TAFI plasma levels were elevated and correlated with acute phase proteins in other noninfectious human diseases, including inflammatory diseases like inflammatory bowel diseases, Reiter's syndrome, Behcet's syndrome, and celiac disease (42,43), and also during coronary artery disease (44) and ischemic stroke (45).…”

Section: Discussionmentioning

confidence: 99%

Absence of Thrombin-Activatable Fibrinolysis Inhibitor Protects against Sepsis-Induced Liver Injury in Mice

Renckens¹,

Roelofs

Horst

et al. 2005

The Journal of Immunology

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Thrombin-activatable fibrinolysis inhibitor (TAFI), also known as carboxypeptidase R, has been implicated as an important negative regulator of the fibrinolytic system. In addition, TAFI is able to inactivate inflammatory peptides such as complement factors C3a and C5a. To determine the role of TAFI in the hemostatic and innate immune response to abdominal sepsis, TAFI gene-deficient (TAFI−/−) and normal wild-type mice received an i.p. injection with Escherichia coli. Liver TAFI mRNA and TAFI protein concentrations increased during sepsis. In contrast to the presumptive role of TAFI as a natural inhibitor of fibrinolysis, TAFI−/− mice did not show any difference in E. coli-induced activation of coagulation or fibrinolysis, as measured by plasma levels of thrombin-anti-thrombin complexes and D-dimer and the extent of fibrin depositions in lung and liver tissues. However, TAFI−/− mice were protected from liver necrosis as indicated by histopathology and clinical chemistry. Furthermore, TAFI−/− mice displayed an altered immune response to sepsis, as indicated by an increased neutrophil recruitment to the peritoneal cavity and a transiently increased bacterial outgrowth together with higher plasma TNF-α and IL-6 levels. These data argue against an important part for TAFI in the regulation of the procoagulant-fibrinolytic balance in sepsis and reveals a thus far unknown role of TAFI in the occurrence of hepatic necrosis.

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“…17 Saibeni et al found that increased TAFI levels (enzyme-linked immunosorbent assay [ELISA]; Affinity Biologicals) might contribute to the prothrombotic state observed in inflammatory bowel syndrome through the induction of hypofibrinolysis. 18 Eichinger et al showed that patients with higher TAFI levels (ELISA; American Diagnostica) have a higher risk for recurrent venous thromboembolism. 19 To date, quantitation of TAFI antigen levels, as a putative risk marker for cardiovascular events, has been mainly focused on "total" antigen levels (either by ELISA or by activity assays after full activation of TAFI), reporting levels of 4 to 15 g/mL.…”

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confidence: 99%

Development of ELISAs Measuring the Extent of TAFI Activation

Ceresa

Brouwers

Peeters

et al. 2006

ATVB

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Objectives-To date, quantitation of TAFI antigen levels has been mainly focused on "total" antigen levels and has been shown to yield ambiguous results because of the existence of different isoforms and various degrees of activation. Our objective was to develop assays that allow measuring the extent of TAFI activation. Methods and Results-A variety of enzyme-linked immunosorbent assays (ELISAs) were evaluated for their preferential reactivity toward TAFI before and after activation, and toward the recombinantly expressed activation peptide. Three ELISAs with distinct reactivities were selected: recognizing either exclusively nonactivated TAFI, the released activation peptide, or exclusively TAFIa (activated TAFI). Evaluation of TAFI activation during clot lysis revealed that decreases of TAFI levels are associated with increases of the released activation peptide and TAFIa levels. In addition, antigenic measurement of TAFIa parallels activity measured by chromogenic assay. Analyzing plasma samples revealed that subjects with hyperlipidemia had significantly higher plasma levels of both the activation peptide (109.2 versus 95.5; PϽ0.001) and TAFIa (112.1 versus 103.3; Pϭ0.03), and not of TAFI antigen (92.5 versus 87.9; Pϭ0.07) (results in % of plasma pooled from normolipidemic subjects). Conclusion-ELISAs that allow to measure the extent of TAFI activation were developed. These ELISAs constitute more sensitive markers in studies on the relationship between TAFI and cardiovascular diseases. ; 36 kDa). Subsequently, TAFIa is inactivated through a conformational change to an inactive form (TAFIai), followed by proteolytic cleavage resulting in fragments of 25 and 11 kDa. 5 TAFIa exerts an antifibrinolytic effect by removing C-terminal lysine residues from fibrin, resulting in a decreased plasmin formation and a retardation of clot lysis. 6 TAFIa is highly unstable in vitro (half-life at 37°C between 8 to 15 minutes). [7][8][9][10] Different clinical studies have investigated the possible relationship between TAFI and cardiovascular events. A positive correlation was found between TAFI levels and the risk for coronary artery disease, 11 venous thrombosis, 12 angina pectoris, 13 and ischemic stroke. 14 However, another study revealed that elevated TAFI may be protective against myocardial infarction. 15 A possible explanation for these contradictory results was that the different studies used different methods for TAFI determination. 16 Silveira et al used quantitative activation of the zymogen followed by determination of the total enzymatic activity with a chromogenic assay. Van of TAFI antigen levels, as a putative risk marker for cardiovascular events, has been mainly focused on "total" antigen levels (either by ELISA or by activity assays after full activation of TAFI), reporting levels of 4 to 15 g/mL. 16,20 -22 However, it should be stressed that in most of these studies the used immunologic assays were not validated with respect to putative differential reactivities toward different isoforms and fragments...

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Assessment of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Plasma Levels in Inflammatory Bowel Diseases

Abstract: TAFI plasma levels are increased in IBD patients and correlate with acute-phase reactants. Increased TAFI plasma levels might contribute to the prothrombotic state observed in IBD through the induction of hypofibrinolysis.

Cited by 56 publications

References 37 publications

Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis

Plasma Thrombin-activatable Fibrinolysis Inhibitor Levels Correlate with the Disease Activity of Ulcerative Colitis

Absence of Thrombin-Activatable Fibrinolysis Inhibitor Protects against Sepsis-Induced Liver Injury in Mice

Development of ELISAs Measuring the Extent of TAFI Activation

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