Thrombin Activatable Fibrinolysis Inhibitor Activity Levels Research Articles

Fetal outcome of meconium-stained infants resuscitated by endotracheal suction versus oropharyngeal suction at birth

Objective Meconium aspiration syndrome (MAS) is one of the most important causes of neonatal intensive care unit admission for full-term newborn infants. We aimed to compare between meconium-stained infants who were intubated at birth and full-term infants who were subjected to oropharyngeal suction of meconium at birth in terms of mortality, MAS, respiratory symptoms, and other clinical outcome measures. We also aimed to evaluate plasma thrombin activatable fibrinolysis inhibitor activity (TAFIa) levels, which may be used as a sign of hypoxia or inflammation in neonates with meconium-stained amniotic fluid (MASF). Patients and methods Seventy five newborn infants delivered through MASF with green-stained vocal cord were studied. The neonates studied were classified into two groups. The first group included 40 neonates with MASF who received endotracheal intubation and airway aspiration at birth. The second group included 35 neonates with MASF who were subjected to oropharyngeal suction at birth. Venous blood sample was drawn from all neonates 6 h after birth to measure plasma TAFIa. Results There was a statistically significant difference in the severity of MAS and respiratory oxygen support, more in the oropharyngeal suction group than in the ETT suction group. There was a highly statistically significant difference in days of oxygen treatment, days of mechanical ventilation, and duration of hospital stay. It was prolonged in the oropharyngeal suction group. Also, there was a highly significant association between poor fetal heart rate tracing pattern and severity of MAS in both groups. Meconium thickness had a significant effect on the severity of MAS in the oropharyngeal suction group than the ETT group. A significant difference was found between plasma TAFIa levels and the severity of MAS, proving that MAS was associated with more acidosis, hypoxia, and depressed fibrinolysis. Conclusion There was a higher incidence and severity of MAS in the oropharyngeal group than the ETT group. Risk factors associated with the development of MAS among infants with MASF include thick meconium, fetal acidosis, nonreassuring fetal heart tracing, and low Apgar score. Also, there was an increase in TAFIa levels in neonates with MASF and this may indicate depressed fibrinolysis.

Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Antigen and Activity Assay in Patients With Primary Hypothyroidism

Hypothyroidism causes a tendency for cardiovascular diseases. It was recently shown that thrombin-activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and also fibrin-plasminogen interaction by the removal of lysine and arginine residues from fibrin monomers. The aim of this study was to determine the effects of overt hypothyroidism on the levels of TAFI antigen (TAFI Ag) and TAFI activity (TAFIa). Thirty-one overt primary hypothyroid patients and age- and gender-matched 25 healthy controls were enrolled in the study. Patients were treated with L-thyroxine after the collection of blood samples. Thyroid functions were reevaluated following the achievement of euthyroid status. Thrombin-activatable fibrinolysis inhibitor Ag, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) levels were measured with the enzyme-linked immunosorbent assay (ELISA). Thrombin-activatable fibrinolysis inhibitor activity was assessed with the chromogenic assay. Thrombin-activatable fibrinolysis inhibitor Ag (1.63% + or - 0.42% vs 1.32% + or - 0.36%, P < .01) and TAFIa (14.2 + or - 4.12 vs 11.6 + or - 3.49 microg/mL, P < .05) levels were elevated in hypothyroid patient compared to controls. Plasminogen activator inhibitor 1 and t-PA levels were not significantly different between both groups. In hypothyroid patients, TAFI Ag levels were correlated with free T(4) (r = -.373, P < .05) and thyroid-stimulating hormone (TSH) levels (r = .748, P < .001). Regression analysis showed that TSH levels were predictors of TAFI Ag levels (P < .001, beta =.671, 95% confidence interval [CI]: 0.008-0.017). Following L-thyroxine treatment, TAFI Ag (1.63% + or - 0.42%, 1.34% + or - 0.33%, P < .05) and TAFIa (14.2 + or - 4.12 microg/mL, 12.0 + or - 2.77 microg/mL, P < .05) levels were significantly decreased, but t-PA and PAI-1 levels remained unchanged. This results point out that the fibrinolytic activity was decreased in hypothyroid patients, and therefore the achievement of euthyroid status is important in ameliorating the increased risk of cardiovascular disease.

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

Studies on the relation between thrombin activatable fibrinolysis inhibitor (TAFI) and arterial thrombosis have produced conflicting results. TAFI regulates fibrinolysis, but other roles of this inhibitor, including anti-inflammatory properties, have also been demonstrated. We investigated the association between TAFI activity and the risk of myocardial infarction. Additionally, we studied the association of common single nucleotide polymorphisms in the TAFI gene with levels of the TAFI protein and risk of myocardial infarction.We included 554 men under 70 years old with a first myocardial infarction and 643 controls participating in the Study of Myocardial Infarctions Leiden (SMILE), a case-control study. We found odds ratios (95% confidence intervals) of a first myocardial infarction of 2.4 (1.6-3.6), 3.2 (2.1-4.7) and 3.4 (2.3-5.1) for subjects whose TAFI levels were in the third, second and first quartiles (lowest TAFI levels), respectively, compared with the fourth quartile, after adjusting for arterial disease risk factors. The rare -438A and 1040T alleles were associated with lower, and the rare 505G allele with higher TAFI levels than the common alleles. Carriers of the -438A allele had an increased risk of myocardial infarction (odds ratio 1.6 (1.0-2.5) for AA; odds ratio 1.2 (0.9-1.5) for AG compared with GG). The other single nucleotide polymorphisms were not associated with myocardial infarction. Low TAFI activity levels are associated with increased risk of a first myocardial infarction in men. The results on the association between TAFI single nucleotide polymorphisms and myocardial infarction were inconsistent.

The Effect of Hormone Replacement Treatment on Thrombin-Activatable Fibrinolysis Inhibitor Activity Levels in Patients with Hashimoto Thyroiditis

Hypothyroid patients have increased risk of cardiovascular diseases, and several mechanisms have been considered responsible in these patients. Although, a few studies demonstrated fibrinolytic system changes in hypothyroid patients, there is no study demonstrating TAFI activity in hypothyroid Hashimoto's thyroiditis patients. The aim of this study was to evaluate TAFI activity status and the effect of L thyroxin hormone replacement treatment on fibrinolytic system in this patient group. Thirty patients with hypothyroid Hashimoto thyroiditis (all were female and the mean age was 44.3+/-14.6 years, ranging between 17-68 years) were enrolled to study. Their TSH levels were high (27.2+/-5.2 mU/L) and Free T3 and Free T4 hormone levels were below than normal. In this study, euthyroid 20 healthy volunteers (mean age 32.5+/-4.9 years, range 26-42 years) were adopted. L-thyroxin treatment before and after TAFI activity levels were measured in patients. In the control group, TAFI activity levels were 9.6+/-0.4 microg/mL. In patients with L-thyroxin before and after treatment there were high levels of TAFI activity value of 14.2+/-0.9 and 12.9+/-0.8 microg/mL, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels were decreased but they were not statistically significant (p=0.187). When compared to the control group, high levels of TAFI activity were observed in the patient group (p<0.0001). Our data demonstrated that in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement.

Fibrinolytic inhibitor levels and polymorphisms in Behçet disease and their association with thrombosis

This study aimed to assess the fibrinolytic inhibitors and their association with thrombosis in Behçet disease. Thrombin activatable fibrinolysis inhibitor (TAFI) (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) levels (P = 0.022) were significantly higher in 79 patients than in 84 controls. No significant differences were observed in CPB2 (TAFI) Thr325Ile and SERPINE1 (PAI1) 4G/5G polymorphism distribution between patients and controls. TAFI activity levels were significantly higher in patients with thrombosis than in those without thrombosis (P = 0.024). In conclusion, the increased TAFI levels in Behçet disease could contribute to the increased risk of thrombosis observed in these patients.

Thrombin-Activatable Fibrinolysis Inhibitor Levels in Patients with Non–Small-Cell Lung Cancer

BACKGROUNDAn increased incidence of thromboembolic events has been described in patients with cancer. Cancer cells are attributed with producing procoagulant substances such as cysteine protease and tissue factor to activate factor X and factor VII, respectively. However, there are limited data on the pathogenesis behind this hypercoagulability state, and the thrombin generation, fibrinolytic system, and coagulation inhibition system during cancer are largely obscure. In this study, we investigated the changes of different steps of coagulation pathway in patients with non–small-cell lung cancer (NSCLC) and compared the data with those of healthy controls. PATIENTS AND METHODSForty-four patients with NSCLC and 36 age-matched controls were recruited for this study. Prothrombin fragment 1 + 2 (F 1 + 2) were used as a marker of thrombin generation; thrombin-activatable fibrinolysis inhibitor (TAFI) immunologic activity level was measured for inhibition of the fibrinolytic system, and tissue factor pathway inhibitor (TFPI) activity was assessed for the coagulation inhibition system. In the patient group, the relationships between TAFI activity levels and patient parameters (age, sex, body mass index [BMI], histopathology, and stage) were evaluated. RESULTSThe TAFI activity, F 1 + 2 levels, and TFPI activity were significantly higher in patients with lung cancer than in subjects in the control group (P < .05; P < .0001; and P < .0001; respectively). However, there were no statistically significant associations between TAFI activity levels and patient age, sex, BMI, histopathology, or stage of disease (P > .05). CONCLUSIONIn this study, it was clearly shown that patients with lung cancer have hypercoagulable states and that the pathogenesis of thrombotic events in these patients is multifactorial. Increased TFPI is a reflection of thrombin activity in this patient group. Confirmatory studies with larger patient groups should be performed in this population.

Thrombin activatable fibrinolysis inhibitor activity (TAFIa) levels in neonates with meconium-stained amniotic fluid

Objective. Meconium-stained amniotic fluid (MSAF) is thought to be a sign of fetal hypoxia, which causes activation of coagulation and inhibition of fibrinolysis. Inflammation is also seen in MSAF. On the other hand, thrombin activatable fibrinolysis inhibitor (TAFI) is an inhibitor of fibrinolysis and a regulator of vascular inflammation. For this reason, in this study we aimed to evaluate the relation between hypoxia, fibrinolysis, and inflammation by determining the levels of TAFI activity (TAFIa) in MSAF where inflammation was also thought to have a role in the pathogenesis.Methods. The MSAF group consisted of 22 neonates; 20 neonates served as the control group. Plasma TAFIa levels were evaluated in all neonates in the first six hours of life.Results. TAFIa levels were significantly higher in the MSAF group when compared with the control group and the levels correlated negatively with cord blood pH levels.Conclusions. Increased TAFIa levels in neonates with MSAF might be due to hypoxia. Inflammation observed in MSAF may also play an additional role in increased TAFIa expression. Although no clinical complication that can be attributed to this increase was seen, one should be alert to the complications of depressed fibrinolysis that might be observed in these neonates.

Thrombin activatable fibrinolysis inhibitor activity, thrombin‐antithrombin complex and D‐dimer levels in preterm neonates with early respiratory distress syndrome

Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, thrombin activatable fibrinolysis inhibitor activity (TAFIa), an inhibitor of fibrinolysis, and the ratio of D-dimer to thrombin-antithrombin complex (D-dimer/TAT), an index of fibrinolytic activity, have not been reported previously in neonatal RDS. Aim of this study is to evaluate the influence of plasma TAFIa levels on the fibrinolytic state in neonatal RDS. The RDS group (Group 1) consisted of 29 neonates, and 18 neonates served as the control group (Group 2). Plasma TAFIa levels and D-dimer/TAT ratios were evaluated in all neonates in the first 6 hr of life. Neonates in the RDS group were further divided into two subgroups; Group 1a consisted of 12 neonates with evidence of mild asphyxia (Apgar score at 5 min <7 and cord pH <7.26), and Group 1b consisted of 17 nonasphyxiated neonates. No significant difference was found in TAFIa levels and D-dimer/TAT ratios between Groups 1 and 2 [214% (56.2-361%) and 124.3 (4.4-3,921) in Group 1 and 201% (60.3-381%) and 147 (5.9-1,426) in Group 2]. There were negative correlations between cord pH and TAFIa levels in both groups. Increased TAFIa levels and decreased D-dimer/TAT ratios and platelet counts were detected in mildly asphyxiated neonates when compared with nonasphyxiated ones. TAFIa is not responsible for the hypofibrinolytic state reported in RDS. However, asphyxia influences TAFIa levels and increased TAFIa levels depress fibrinolysis.

ASSESSMENT OF THE ROLE OF THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR IN RETINAL VEIN OCCLUSION

To determine whether elevated levels of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to thrombotic risk for patients with retinal vein occlusion (RVO) and to investigate the possible correlations between TAFI activity level and other conventional risk factors. Ninety patients with RVO (cases), except those receiving medication affecting the study parameters, those undergoing a surgical procedure within the last week, and those with kidney and/or liver failure, were enrolled in the study. The control group included similar patients matched for age and sex. After written informed consent was obtained, parameters including TAFI activity levels, conventional risk factors, results of routine hematological examination, and factor V Leiden and prothrombin G20210A mutations were evaluated by analysis of blood samples obtained after an 8-hour fast. Although TAFI activity levels were slightly elevated in cases (190.5 +/- 43.8) compared with controls (183.9 +/- 41.8), the difference was not statistically significant (P = 0.36). According to evaluation of TAFI activity in subgroups (>200%, 150-200%, and 0-150%), 36.7% with central RVO, 40.0% with branch RVO, and 30% of controls were found to have TAFI activity of >200% (P = 0.83). TAFI activity levels did not correlate with age, sex, demographics, clinical status, and hematological variables. Finally, in stepwise regression analysis, TAFIa (carboxypeptidase U) activity was not found to be an important risk factor for RVO. On the basis of these data, TAFI activity was not found to be a new risk factor for either type of RVO. However, further larger studies may better identify the exact role of TAFI in the pathogenesis of RVO.

Plasma activity of thrombin activatable fibrinolysis inhibitor in Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal viral infection. The exact mechanism for hemorrhage remains unknown. Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma procarboxypeptidase B-like proenzyme and synthesized in the liver, down-regulating fibrinolysis. In this study, we measured the TAFI activity in plasma of patients with CCHF to examine the relationship between hemorrhage and the pathogenesis of CCHF. Twenty-one patients and similar number of controls were included in the study. The diagnosis of CCHF was confirmed through detection of IgM by ELISA and/or PCR. TAFI activity was measured in plasma samples. TAFI activity in CCHF patient group was mean 7.2+/-2.3 microg/ml (range: 0.95-10.31 microg/ml) and in the control group was mean 11.7+/-4.1 microg/ml (range: 3.07-23.9 microg/ml). There was a significant decrease of TAFI activity in CCHF patients when compared to controls. A positive correlation between CRP, PT, INR, serum albumin and TAFI activity levels were found. We suggest that the decrease of TAFI activity may be due to liver dysfunction during viral active disease state. Low TAFI activity may be an attributable factor, leading to imbalance in fibrinolysis, resulting in bleeding complications in CCHF.