Thrombin Activatable Fibrinolysis Inhibitor Levels In Patients Research Articles

Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels and TAFI Gene Polymorphisms in Patients with Budd-Chiari Syndrome and Portal Vein Thrombosis.

Background Budd-Chiari syndrome (BCS) and Portal Vein Thrombosis (PVT) have been associated with several hypercoagulable states. Thrombin-activatable fibrinolysis inhibitor (TAFI) potently attenuates fibrinolysis. Elevated TAFI antigen levels form a risk factor for deep venous thrombosis and are to a high extend genetically determined. To establish the pathogenetic role of TAFI in BCS and PVT, we studied TAFI antigen levels and gene polymorphisms in patients with BCS, PVT and matched controls.Methods In a multicenter case-control study, 39 patients with BCS, 85 patients with PVT and 118 population-based controls were identified. Plasma levels of TAFI antigen were determined by a commercially available ELISA and polymorphisms of the TAFI gene (TAFI 505A/G and TAFI 1040C/T) were analysed by PCR. Because TAFI antigen levels are decreased in patients with impaired liver synthesis, plasma levels were corrected for antithrombin activity levels. ANOVA techniques were used to correlate TAFI polymorphisms with TAFI antigen levels.Results Mean plasma TAFI antigen levels were significantly lower in BCS and/or PVT patients as compared to controls, even after adjusting for impaired liver function by antithrombin activity levels (all p<0.002). There was a strong correlation between the TAFI 505 A/G and TAFI 1040 C/T polymorphisms and plasma TAFI antigen levels in all groups (all p<0.001). The G-allele of the 505A/G polymorphism was associated with a low antigen level of TAFI. Carriers of the GG genotype had an increased risk for BCS and/or PVT (OR=4.4; 95% CI 1.5–12.6). Carriers of the G allele showed a risk of 4.1 (95% CI 1.5–11.5). For the 1040C/T polymorphism, the T allele was associated with lower levels of TAFI antigen, and carriers of at least one copy of the T allele showed an OR of 1.6 (95% CI 0.9–2.7).Conclusion We found lower TAFI levels in patients with BCS and/or PVT than in healthy controls. In addition two TAFI genotypes, associated with lower TAFI antigen levels were found more frequently in patients with BCS and/or PVT than in healthy controls. Therefore low TAFI levels appear to be a risk factor for the development of BCS and PVT. These results suggest a different pathogenetic mechanism of TAFI in BCS and PVT than in deep venous thrombosis.

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

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.

Thrombin activatable fibrinolysis inhibitor

The slow coronary flow (SCF) phenomenon is characterized by slow progression of angiographic contrast medium in the coronary arteries in the absence of stenosis in the epicardial vessels. The pathophysiological mechanisms of SCF phenomenon remain uncertain. Several hypotheses, however, have been suggested for SCF phenomenon, including an early form of atherosclerosis, small vessel dysfunction, dilatation of coronary vessels, imbalance between vasoconstrictor and vasodilatory factors, platelet function disorder, and inflammation. Atherosclerosis and inflammation are the most accepted mechanisms for the pathogenesis of SCF. Thrombin activatable fibrinolysis inhibitor (TAFI) was described as a new inhibitor of fibrinolysis recently and plays an important role in coagulation and fibrinolysis. In previous studies, the role of TAFI was associated with inflammation and evolution of atherosclerosis in coronary artery disease. There are no data available about TAFI levels in patients with SCF phenomenon investigated by angiography. Our goal was to evaluate TAFI antigen (Ag) levels in patients with SCF and to determine the association of the TAFI Ag level with traditional cardiovascular risk factors in our study. The study group constituted 41 patients with angiographically confirmed SCF and 46 patients with normal coronary flow as the control group. The TAFI Ag levels of each patient were determined. Between the control and study group, a statistical difference in the levels of TAFI Ag (p < 0.05) was observed. The TAFI Ag level was significantly higher in the SCF group than the control group (132.21 ± 21.14 versus 122.15 ± 21.59). We have demonstrated that TAFI might be a risk factor for the development of SCF independently of conventional cardiovascular risk factors. In addition, TAFI Ag levels were positively correlated with C-reactive protein (CRP) known as an acute phase reactant. Our findings support the reports of previous studies that increased TAFI levels may be associated with inflammation. Further large studies are required to evaluate the importance of TAFI antigen levels in relation to the development of SCF.

Plasma thrombin-activatable fibrinolysis inhibitor as an indicator of inflammation and disease severity in acute pancreatitis

In addition to suppressing fibrinolysis, thrombin activatable fibrinolysis inhibitor (TAFI) was suggested to be involved in inflammation. To date, no study has been published that reports the role of TAFI in acute pancreatitis (AP). Therefore, the objective of the present study was to investigate the role of plasma TAFI as an indicator of inflammation in AP, and its association with disease severity. Plasma TAFI antigen levels quantitatively determined by using ELISA kits in 21 AP patients at onset and remission and 17 healthy controls. Associations of TAFI with inflammatory markers to determine AP and disease severity were assessed. To predict the severity of AP, modified Glasgow prognostic score (mGPS) and computerized tomography severity index (CTSI) were used for each subject. Plasma TAFI levels was higher in AP patients at onset of the disease compared with healthy controls. The disease severity according to mGPS was significantly correlated with TAFI levels. Overall, accuracy of TAFI in determining AP was 83.3% with a sensitivity, specificity, NPV and PPV of 80.9%, 85.7%, 81.8%, and 85% respectively (AUC: 0.915). The present study for the first time demonstrated that TAFI is elevated in AP. The appraisal of TAFI levels in patients with AP in conjunction with other markers of inflammation may provide additional information in estimating AP severity.

Serum thrombin activatable fibrinolysis inhibitor levels in patients with newly diagnosed multiple myeloma

Multiple myeloma has been associated with the development of thromboembolic events. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, which potently inhibits fibrinolysis. The purpose of the present study was to assess the TAFI levels in patients with newly diagnosed multiple myeloma. Twenty-seven newly diagnosed multiple myeloma patients (16 women and 11 men) and 27 age-matched healthy individuals (14 women and 13 men) were included in the study. Serum TAFI levels were significantly increased in patients with multiple myeloma (46 ± 13. 3 vs. 36. 6 ± 9.7 μg/ml) compared with healthy individuals. Serum TAFI levels were negatively correlated with serum albumin (CC: -0.453, P < 0.05) and hemoglobin levels (CC: -0.392, P < 0.05) and positively correlated with the β-2 microglobulin levels (CC: 0.524, P < 0.05). In this study, we observed significantly elevated TAFI levels in patients with multiple myeloma and higher serum TAFI levels were suggested to be associated with higher disease stage. With these results, a possible role of elevated TAFI levels in thromboembolic manifestations in the course of multiple myeloma can be suggested.

Role of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with acute pulmonary embolism

Thrombin activatable fibrinolysis inhibitor (TAFI) is involved in the regulation of the balance between coagulation and fibrinolysis. After activation by the thrombin‐thrombomodulin complex, TAFI downregulates plasmin formation, and thereby inhibits degradation of the fibrin clot [1]. High TAFI plasma levels may therefore contribute to an increased risk of thrombotic disorders. Elevated TAFI levels were found in patients with coronary artery disease [2,3]. In patients with venous thrombosis, TAFI levels above the 90th percentile were associated with an increased risk of thrombosis [4]. There are no data available on the role of TAFI levels in patients with pulmonary embolism (PE). The aim of the present case-control study was to examine TAFI antigen levels in relation to markers of coagulation and fibrinolysis in patients with and without acute PE. We investigated 120 patients with suspected PE and D-dimer levels � 500 ng mL � 1 . PE was diagnosed in 71 patients and excluded in 49 patients with a diagnostic strategy including pretest probability and spiral computed tomography (CT) [5]. In patients with proven PE, pulmonary occlusion rate was assessed by spiral CT using the modified Miller index described by Remy-Jardin et al. [6]. Deep vein thrombosis (DVT) was confirmed by compression sonography in 16 and excluded in 50 patients with confirmed PE and clinically suspected DVT. All patients gave written informed consent according to a protocol approved by the local ethics committee. Blood samples were drawn from an antecubital vein within 1 h after admission of the patients. Coagulation assays were performed in citrated plasma, C-reactive protein (CRP) was measured in heparinized blood samples. Total TAFI antigen levels were determined by an enyzme-linked immunosorbent assay (ELISA) (Milan Analytica, La Roche, Switzerland). TAFI levels were expressed as percentage of normal pooled plasma. Fibrinogen levels were measured according to Clauss, and D-dimer levels using an automated ELISA techni