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The main objective of the study is to compare the impacts of laparoscopic hysterectomy and total abdominal hysterectomy on the functions of coagulation and fibrinolysis system. Seventy-five patients who had undergone hysterectomy were randomly divided into laparoscopic hysterectomy group (n = 38) and total abdominal hysterectomy group (n = 37). The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, D-dimer, von Willebrand factor, α-granule membrane protein-140, thrombin-activated fibrinolysis inhibitor (TAFI) and platelet count were detected at preoperative 24 h (N0), postoperative 24 h (N1) and postoperative 48 h (N2). Compared with N0, values of PT, APTT and TT were significantly decreased at N1 in both groups, whereas von Willebrand factor, platelet count and α-granule membrane protein-140 levels at N1 were significantly increased (P < 0.05). There was no significant difference between N0 and N2 (P > 0.05). Compared with N0, fibrinogen, D-dimer and TAFI levels in both groups were significantly higher at N1 (P < 0.05), and there was no significant difference between N0 and N2 (P > 0.05). The intergroup comparison showed no significant difference of above indexes between two groups (P > 0.05). The univariate analysis showed that TAFI was negatively correlated with TT (r = -0.365, P < 0.01), APTT (r = -0.183, P < 0.05) and PT (r = -0.121, P < 0.05), whereas not correlated with other indicators. Laparoscopic hysterectomy may increase the risk of postoperative venous thrombosis.

Thrombin activatable fibrinolysis inhibitor (TAFI) is an important procoagulant factor. Patients with metabolic syndrome (MetS) also have an elevated procoagulant status. However, TAFI and its association with MetS are still not well known. We aimed to investigate TAFI in type 2 diabetes mellitus patients with MetS. We enrolled a total of 55 patients who had MetS (n = 30) and 25 healthy controls. MetS was diagnosed using National Cholesterol Education Program Adult Treatment Panel III criteria. We measured activated and inactivated TAFI (TAFIa/ai) antigen in plasma samples using a commercially available ELISA kit (Imubind TAFIa/ai antigen ELISA; American Diagnostica Inc., Stamford, Connecticut, USA). TAFIa/ai levels were then evaluated for links to MetS parameters. Mean TAFIa/ai levels were 156.6 ± 66.9 ng/dl in patients with MetS and 104.1 ± 60.3 ng/dl in the control group (P = 0.005). None of the MetS parameters, including blood pressure, fasting plasma glucose, waist circumference, triglycerides or high-density lipoprotein cholesterol (HDL-C) levels were correlated with TAFIa/ai levels. However, TAFIa/ai level had a strong correlation with the number of metabolic risk components, which increased proportionally when MetS parameters were over three. When there were increased numbers of MetS risk components, we detected a rise in TAFIa/ai levels. TAFIa/ai levels could be an indicator of atherosclerotic tendency in patients with MetS.

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.

Disturbances of coagulation and fibrinolysis in type 2 diabetes mellitus (DM2) contribute to increased rates of macrovascular complications such as myocardial infarction and ischemic stroke. The aim of the study was to investigate the relationship among plasminogen activator inhibitor 1 (PAI-1), thrombin-activable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (t-PA), prothrombin fragments 1+2 (F1+2), glycemic control, hypertension, sex and body mass index (BMI) in DM2 patients with normoalbuminuria and microalbuminuria. Forty-two normoalbuminuric (NAU), 42 microalbuminuric (MAU) patients with DM2 and 42 blood donors as control group were enrolled. TAFI, PAI-1, t-PA and F1+2 were assessed by enzyme-linked immunosorbent assay (ELISA) in all patients. TAFI was significantly increased in the MAU group, PAI-1 and F1+2 were increased in both groups and t-PA was not elevated in either group compared to controls. We found positive correlations in the NAU: TAFI and fibrinogen (r=0.65, P=0.02), PAI-1 and triglycerides (r=0.67, P=0.01), in the MAU: TAFI and F1+2 (r=0.48, P=0.02), TAFI and systolic blood pressure (r=0.53, P=0.01), PAI-1 and BMI (r=0.43, P<0.05). We found decreased fibrinolysis in DM2 patients presented with increased PAI-1 in both NAU and MAU. Hypofibrinolysis in MAU is further accented by the elevation of TAFI. TAFI-mediated inhibition of fibrinolysis in DM2 is regulated independently from PAI-1. Patient[Combining Acute Accent]s sex does not affect diabetes-related changes in hemostasis and fibrinolysis.

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.

Recurrent fetal loss (RFL) is common health problem affecting up to 5% of women of reproductive age. It has been shown that plasma thrombin-activatable fibrinolysis inhibitor (TAFI) concentrations increase during pregnancy and return to baseline levels soon after delivery. The +1040C/T single nucleotide polymorphism in coding region of TAFI gene is associated with TAFI blood levels. The aim of our study was to investigate the relationship between +1040C/T polymorphism in TAFI gene and idiopathic RFL. Study was carried out in a group of 120 women (61 controls and 59 women with idiopathic RFL). The +1040C/T polymorphism was detected by restriction fragment length polymorphism PCR. Increased frequency of +1040T/T genotype was observed in a study group, but without statistically significant difference. Carriers of T/T genotype have increased risk of fetal loss by 1.23-fold, compared with carriers of C/C (95% CI 0.462-3.277; P = 0.7) and 1.34-fold compared with carriers of C/T genotype (95% CI 0.501-3.601; P = 0.6). C allele is associated with reduced risk of recurrent fetal loss compared with T allele (OR 0.91; 95% CI 0.545-1.533; P = 0.7). In conclusion, we observed increased frequency of +1040T/T genotype in a patient group, suggesting that this genotype could be potential risk factor for idiopathic RFL. Further investigation should be carried out in order to establish the role of this polymorphism in the etiology of idiopathic recurrent miscarriages.

In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD.

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of thromboembolic events. Imbalance of fibrinolysis has been suggested as one of the possible pathogenetic mechanisms. As plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are inhibitors of fibrinolysis, we studied TAFI as well as PAI-1 plasma levels in IBD patients compared with healthy controls., Methods: A total of 132 IBD patients [68 ulcerative colitis (UC) and 64 Crohn's disease (CD)] and 50 healthy controls were enrolled. PAI-1 and TAFI plasma levels were assessed by commercially available enzyme-linked immunosorbent assay kits. Their relationship with clinical parameters of UC and CD was assessed., Results: Mean plasma PAI-1 levels were significantly higher in both UC patients (3.9+/-1.3 IU/ml) and CD patients (4.0+/-1.5 IU/ml) compared with healthy controls (3.1+/-1.1 IU/ml) (P=0.01). On the other hand, mean plasma TAFI levels were significantly lower in both UC patients (14.7+/-3.1 microg/ml) and CD patients (13.3+/-3.4 microg/ml) compared with healthy controls (17.4+/-3.0 microg/ml) (P<0.0001). Patients with active disease had significantly higher PAI-1 levels compared with patients with inactive disease for both diseases (P=0.03 and P=0.01, respectively). No significant association between plasma TAFI levels and disease activity was also found. Plasma TAFI levels were significantly lower in patients with ileal CD compared with patients with colonic CD., Conclusion: PAI-1 plasma levels are increased whereas TAFI levels are decreased in IBD patients. These results suggest an imbalance of fibrinolysis in IBD.

To investigate thrombin activatable fibrinolysis inhibitor (TAFI) in ischemic stroke and its relationship to fibrinolysis and inflammation, we investigated 32 patients with ischemic stroke during the acute phase and after 60 days. TAFI antigen levels, global markers of hemostasis (coagulation and fibrinolysis) and inflammatory markers were measured in plasma. TAFI antigen levels were significantly elevated at admission (128%; 109-151%) and at day 1 (129%; 109-152%) compared with day 60 (108%; 91-127%; both P < 0.01) and with healthy control individuals (99%; 76-122%; P < 0.05). In parallel, fibrinolysis assessed as the overall fibrinolysis potential (OFP), part of the overall hemostatic potential assay (OHP), was decreased at all time points compared with control individuals (P < 0.01 for all) and was found to be inversely related to TAFI (r = -0.40; P = 0.0008; n = 20). The OFP and the overall coagulation potential (another part of the OHP assay), and to a lesser degree TAFI, showed significant relationships to C-reactive protein and fibrinogen. In conclusion, elevated TAFI antigen levels may be a consequence of an acute phase reaction, and together with a depressed OFP suggest impaired fibrinolysis in patients with acute ischemic stroke. The OHP method may be useful as a complement to standard hemostatic variables in evaluating hemostasis in stroke patients.

To investigate the importance of thrombin activatable fibrinolysis inhibitor (TAFI) in the stabilization of plasma clots, we have compared fibrinolysis in TAFI-deficient (KO) and wild-type (WT) littermate mice. TAFI-deficient mice were previously generated by targeted gene disruption. The level of TAFI activity generated in plasma from WT mice in the presence of added thrombin and thrombomodulin (activatable TAFI) is twice that of plasma from TAFI heterozygous mice (HET); no activatable TAFI is detected in TAFI KO plasma. In vitro, TAFI KO plasma clots lysed faster than WT plasma clots, and HET plasma clots lysed at an intermediate rate. The rate of clot lysis for KO mice is not changed in the presence of potato carboxypeptidase inhibitor, a specific inhibitor of TAFIa, whereas the WT and HET clot lysis rates are increased in the presence of potato carboxypeptidase inhibitor. C-terminal lysine residues are preserved on partially degraded clots from KO mice, but are absent from partially degraded WT clots. In vivo, in a batroxobin-induced pulmonary embolism model, KO mice displayed a lower retention of fibrin in the lungs than did WT mice. These results are the first demonstration of enhanced endogenous fibrinolysis in an in vivo model without the addition of exogenous thrombolytic.

The aim of our study was to investigate the effect of two different hyperbaric exposures followed by decompression on thrombin activatable fibrinolysis inhibitor (TAFI) concentration and activity. The hyperbaric conditions correspond to diving to 30 and 60 m water depth. Thirty-four male divers were tested in decompression habitat LSH-200, with air as a breathing medium. The pro-enzyme and total TAFI antigen concentration were measured. We did not observed significant changes of either pro-enzyme or total TAFI antigen concentration after both series of exposures followed by decompression. The results may suggest that TAFI plays only a marginal role, if any, in the regulation of induced fibrinolysis in divers, which may contribute to bleeding episodes in a course of decompression sickness.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.

Thromboembolic complications are often seen in patients with nephrotic syndrome. Markers of endothelial cell injury [thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule, thrombin activatable fibrinolysis inhibitor (TAFI), protein Z, vascular endothelial growth factor, markers of thrombin and plasmin generation] were studied in 22 patients with nephrotic syndrome. All these parameters studied, except protein Z and D-dimers, were significantly higher in patients with nephrotic syndrome, whereas protein Z was significantly lower when compared with the healthy volunteers. None of the endothelial cell markers (thrombomodulin, P-selectin, E-selectin, intracellular adhesion molecule, vascular cell adhesion molecule), thrombin and plasmin generation markers (thrombin-antithrombin complexes, prothrombin fragments 1 + 2, plasmin-antiplasmin complexes, D-dimers), protein C, protein Z, vascular endothelial growth factor, and TAFI concentration and activity were directly correlated with the level of proteinuria, albumin, cholesterol, triglycerides or creatinine, except significant positive correlations between TAFI activity and serum creatinine, E-selectin and albumin as well as negative correlations between plasmin-antiplasmin complexes and proteinuria. In these patients, there is evidence of endothelial cell injury and probably secondary activation of the coagulation cascade. Elevated circulating TAFI antigen and activity might be a new link in the pathogenesis of impaired fibrinolysis and the progression of atherosclerosis in nephrotic syndrome. Protein Z deficiency might also contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome.