Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Before hemodialysis (HD), plasma levels of tissue factor (TF), free-TF pathway inhibitor (TFPI) and thrombomodulin (TM) were significantly higher in patients with HD than in healthy volunteers. Plasma levels of (T-F) TFPI and plasmin plasmin inhibitor complex (PPIC) were significantly higher in patients with HD than in healthy volunteers. During HD, plasma levels of TF and (T-F) TFPI were not significantly increased, but plasma levels of total TFPI and free TFPI at 1 hour after and at the end of HD were significantly increased, compared with levels before start of HD. Plasma level of PPIC 1 hour after start of HD was significantly higher than before start of HD, and plasma levels of thrombin antithrombin complex (TAT), PPIC, D-dimer, TM, and protein C (PC) at the end of HD were significantly higher than before start of HD. In patients with thrombosis complications, plasma TF levels were significantly higher than in patients without thrombotic complications during HD. Plasma levels of PC were significantly lower in patients with thrombotic complications than in patients without thrombotic complications. There was no significant difference between both groups during HD in hemostatic parameters, with the exception of TF and PC. Hemostatic abnormalities existed in patients with HD; especially, increased TF and decreased PC might cause thrombotic complications.
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PMID:Hemostatic abnormalities in patients with thrombotic complications on maintenance hemodialysis. 1077 31

We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 +/- 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.
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PMID:Increased hemostatic molecular markers in patients undergoing anticoagulant therapy. 1080 92

Thromboembolism is a serious complication after Fontan operation, which may be caused by alterations of the coagulation system. We therefore investigated pro- and anticoagulant factors in 20 patients aged 4 to 21 years, 4 to 63 months following total cavopulmonary connection. Furthermore we compared markers of thrombin activation and fibrinolysis and in vitro clotting and clot-lysis to age-matched healthy subjects. Compared to results of age-matched controls, the Fontan operated individuals had significant decreases in levels of protein C (0.88 U/ml in controls, 0.67 U/ml in patients; p <0.001) and protein S (1.05 in controls, 0.93 U/ml in patients; p <0.05). Moreover, half of the patients had high values of FVIII (>1.5 IU/ml), which are associated with an increased thrombotic risk. These changes may result in enhanced generation of thrombin and plasmin, indicated by our finding of increased thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) levels and a similar trend in prothrombin fragments F1+2. Clot lysis tests, global coagulation tests, red blood cell count, liver enzymes AST, ALT, but not GGT, were generally within the normal ranges.
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PMID:Hemostatic changes following the modified Fontan operation (total cavopulmonary connection). 1181 32

Background: Reduced levels of protein S (PS) and alpha(2)-antiplasmin alpha(2)-AP) in solvent/detergent virus-inactivated plasma (S/D-VIP) might induce an imbalance of plasma coagulation factors and inhibitors in patients transfused. We investigated 40 patients (23 fresh frozen plasma (FFP), 17 S/D-VIP, random distribution by a list calculated by statisticians) who suffered from dilution coagulopathy, liver disease, disseminated intravascular coagulation (DIC), polytrauma or were connected to extracorporeal circulation. Study Design and Methods: The following markers of activated coagulation (MAC) were measured: Prothrombin fragment F1+2 (F1+2), fibrin monomers (FM), D-dimers (DD), thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes as well as fibrinogen degradation products (FgDP), and additionally antithrombin III (antithrombin), protein C (PC), PS and alpha(2)-AP. Blood was taken only just before and 1 h after the first plasma replacement (2 units). No additional blood products were transfused before the second blood withdrawal. Pre- and posttransfusion (pre/post) values of all parameters measured were compared within the same group and between both groups. Statistical evaluation of the data was done by Wilcoxon's paired test for data in the same plasma group and by the test of Mann and Whitney for data comparison between both plasma groups. Results: Average pretransfusion values of all inhibitors for both plasma groups were in the same range and increased after transfusion, except for PS in both groups. Whereas the pre/post values did not differ significantly in the FFP group, antithrombin (p = 0.02), PC (p = 0.0005), and alpha(2)-AP (p = 0.02) showed a significantly higher increase in the S/D-VIP group. Considering the pre/post differences between both plasma groups, there were no significant differences. The same was true for MAC measured pre- and posttransfusion. Conclusion: Data showed no significant difference between both plasma groups, indicating that S/D-VIP plasma behaves as FFP under the study conditions employed. Copyright 2000 S. Karger GmbH, Freiburg
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PMID:Comparison of Solvent/Detergent-Inactivated Plasma and Fresh Frozen Plasma under Routine Clinical Conditions. 1087 83

A series of 12 bovine pancreatic trypsin inhibitor variants mutated in the P(4) and P(3) positions of the canonical binding loop containing additional K15R and M52L mutations were used to probe the role of single amino acid substitutions on binding to bovine trypsin and to the following human proteinases involved in blood clotting: plasmin, plasma kallikrein, factors X(a) and XII(a), thrombin, and protein C. The mutants were expressed in Escherichia coli as fusion proteins with the LE1413 hydrophobic polypeptide and purified from inclusion bodies; these steps were followed by CNBr cleavage and oxidative refolding. The mutants inhibited the blood-clotting proteinases with association constants in the range of 10(3)-10(10) m(-)(1). Inhibition of plasma kallikrein, factors X(a) and XII(a), thrombin, and protein C could be improved by up to 2 orders of magnitude by the K15R substitution. The highest increase in the association constant for P(3) mutant was measured for factor XII(a); P13S substitution increased the K(a) value 58-fold. Several other substitutions at P(3) resulted in about 10-fold increase for factor X(a), thrombin, and protein C. The cumulative P(3) and P(1) effects on K(a) values for the strongest mutant compared with the wild type bovine pancreatic trypsin inhibitor were in the range of 2.2- (plasmin) to 4,000-fold (factors XII(a) and X(a)). The substitutions at the P(4) site always caused negative effects (a decrease in the range from over 1,000- to 1.3-fold) on binding to all studied enzymes, including trypsin. Thermal stability studies showed a very large decrease of the denaturation temperature (about 22 degrees C) for all P(4) mutants, suggesting that substitution of the wild type Gly-12 residue leads to a change in the binding loop conformation manifesting itself in non-optimal binding to the proteinase active site.
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PMID:Inhibition of six serine proteinases of the human coagulation system by mutants of bovine pancreatic trypsin inhibitor. 1093 Apr 17

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.
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PMID:Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states. 1093 61

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.
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PMID:Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. 1102 Apr 68

Hepatic veno-occlusive disease (VOD) is a major complication after hematopoietic stem cell transplantation (HSCT). Aetiological determinants, diagnosis and treatment remain unclear. Changes in coagulation-fibrinolysis parameters and N-terminal propeptide for type III procollagen (P-III-P) have been studied in patients with or without VOD after HSCT. We prospectively measured protein C activity, tissue plasminogen activator (t-PA), antithrombin III (AT-III), plasminogen activity (PLG), thrombin-antithrombin III (TAT), alpha2-plasmin inhibitor (alpha2-PI),fibrinogen (Fbg) and P-III-P in 44 consecutive adult patients undergoing allogeneic HSCT. Each parameter was determined before conditioning, on day 0 of HSCT and weekly for 5 weeks. Five of the 44 patients developed VOD at a median post HSCT of day 3 (range, day 3 to 12). On repeated analysis of variance (ANOVA), there were significant differences between patients with and without VOD in P-III-P (P < 0.0001), protein C (P < 0.0001), t-PA (P < 0.0001), PLG (P < 0.0001), AT-III(P < 0.0001), Fbg (P < 0.0001), alpha2-PI (P = 0.0002). Levels of P-III-P were significantly higher in patients with VOD than without VOD, before preparative chemotherapy (P < 0.005) and on days 0 and 7 (P < 0.001). On day 0, levels of t-PA were significantly higher in patients with VOD than without VOD (P < 0.05). On day 7, levels of protein C were significantly lower in patients with VOD than without VOD (P < 0.01). On day 0, there were trends of differences (P = 0.0515) between patients with and without VOD in the levels of protein C. These results suggest P-III-P, t-PA and protein C are predictive markers for VOD after HSCT in adults. Moreover, the serum P-III-P level before start of conditioning might indicate patients at risk for developing VOD.
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PMID:Predictive markers for hepatic veno-occlusive disease after hematopoietic stem cell transplantation in adults: a prospective single center study. 1108 89

To study the in vivo effect of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As(2)O(3) therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.
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PMID:Effects of all-trans-retinoic acid and arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia. 1136 12

We investigated coagulation/fibrinolysis parameters for significant differences between patients with early-onset severe preeclampsia (< 32 weeks gestation, wG) and those with late-onset severe preeclampsia (> or = 32 wG). A decrease in antithrombin (AT), protein C (PC), and free protein S (PS) activities and an increase in plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin complex (TAT), and FDP D-dimer (D-dimer) were observed. However, there were no statistical differences between the two groups. Once preeclampsia occurred and it developed severe, the changes in coagulation/fibrinolysis parameters became more severe in spite of early-onset preeclampsia or late-onset preeclampsia. We also investigated coagulation/fibrinolysis abnormalities in 101 patients with severe preeclampsia. A significant increase in WBC, RBC, Hb, Ht, TAT, PIC, and D-dimer and a significant decrease in platelet (Plt) counts and AT activity were observed. deltaPlt (the difference between platelet counts in early gestation and before delivery) was -5.0 x 10(4)/microL in cases with severe preeclampsia. Among patients with severe preeclampsia, coagulation/fibrinolysis changes before delivery were typical for patients with cesarean section compared with those with successful vaginal delivery. These facts suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting from the aggravation of preeclampsia. From the viewpoint of coagulation/fibrinolysis changes, the termination of pregnancy could be recommended when the levels of parameters exceed the following values; deltaPlt > -6.0 x 10(4) microL, D-dimer > 4 microg/mL, AT activity < 79%, TAT > 26 ng/mL, and PIC > 1.2 microg/mL. Particularly, deltaPlt and D-dimer are useful bedside predictive markers in order to decide the optimal time for the termination of pregnancy in patients with severe preeclampsia.
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PMID:Predictive values of coagulation/fibrinolysis parameters for the termination of pregnancy complicated by severe preeclampsia. 1137 67


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