Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This preliminary report outlines the rationale for a new approach to deep-vein thrombosis (DVT) prophylaxis in total knee arthroplasty (TKA) patients and describes preliminary hematologic and venographic findings. A protocol was employed to (1) document a series of hematologic events surrounding cemented TKA and the alterations of these events by the study drugs and (2) compare the safety and efficacy of a regimen of antithrombin III/low-dose heparin (ATIII/LDH) to that of low-molecular-weight dextran (LMWD) in the prevention of DVT after TKA. Using a dosage regimen of 3000 units of ATIII as a loading dose followed postoperatively by 2000 units daily combined with 5000 units of LDH twice daily, a prospective randomized study of patients treated by cemented TKA was performed. The ATIII/LDH regimen was compared with LMWD (10 ml/kg x 12 hours loading dose followed by 7 ml/kg x 24 hours maintenance dose). The rate of DVT after TKA in 42 patients was 25% (5/20) for the ATIII/LDH group versus 82% (18/22) for the LMWD group (p less than 0.001). Bleeding complications were minimal and comparable for each group. Hematologic studies demonstrated that quantitative and functional ATIII levels decreased after TKA and that preoperative loading with ATIII prevented levels from falling below 100%. Studies of clot formation (fibrinopeptide A) and plasmin activity (fibrinopeptides B beta 15-42 and 1-42) in 34 patients suggest some reduction in procoagulant activity in patients in the ATIII/LDH group. These findings indicate that the combination of ATIII and LDH may offer superior protection from DVT than does LMWD.
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PMID:Antithrombin III/low-dose heparin in the prevention of deep-vein thrombosis after total knee arthroplasty. A preliminary report. 247 30

Thrombotic thrombocytopenic purpura (TTP) is thought to be caused primarily by endothelial cell injury or primary platelet agglutination. A coagulation screen usually shows normal or minimal changes, but a modest elevation of fibrinogen/fibrin degradation products (FDP) is observed in many patients with TTP. To assess the thrombin generation in vivo in TTP, plasma levels of thrombin-antithrombin III complex (TAT) were measured together with plasmin-alpha 2-antiplasmin complex (PAP) in ten patients with acute TTP. Plasma TAT [mean 6.7 +/- (SD) 3.7 micrograms/liter] as well as PAP (2.1 +/- 1.2 mg/liter) were elevated in patients with TTP as compared with healthy subjects (TAT of 1.7 +/- 0.3 microgram/liter and PAP of 0.2 +/- 0.1 mg/liter; n = 10). These findings indicate that considerable amounts of thrombin and plasmin are actually generated in TTP, although the majority of patients do not show signs of consumption coagulopathy.
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PMID:Thrombin generation in patients with thrombotic thrombocytopenic purpura. 247 64

The activity of tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) is stimulated by heparin. Heparin binds tightly to t-PA, u-PA, and plasminogen and decreases the usual stimulatory effect of fibrin on t-PA activity. In the present study we have found that low molecular weight heparin (LMW-heparin) preparations obtained by nitrous acid depolymerization or heparinase treatment of standard heparin have different properties with respect to their interaction with the fibrinolytic system. LMW-heparin prepared by either method does not stimulate plasmin formation by t-PA. However, these preparations of heparin still efficiently accelerate the inhibition of thrombin by antithrombin III. Binding data show that LMW-heparin does not bind t-PA and Glu-plasminogen and only binds very weakly to Lys-plasminogen. These results illustrate that it is possible to selectively destroy the fibrinolytic stimulating properties of heparin while leaving the classical anticoagulant characteristics intact.
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PMID:Anticoagulant low molecular weight heparin does not enhance the activation of plasminogen by tissue plasminogen activator. 250 19

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
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PMID:Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. 252 Dec 76

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
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PMID:Thrombin and plasmin generation in patients with liver disease. 252 2

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.
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PMID:Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. 238 33

Pancreatic pseudocyst fluid from eight patients was examined biochemically. The fluid was found to be a mixture of plasma proteins and pancreatic juice, possessing a high proteolytic activity against high- as well as low-molecular-weight proteins. The proteolytic activity was found to be trypsin-, kallikrein- and plasmin-like. Gel filtration studies showed proteolytic activity to be present corresponding to alpha-2-macroglobulin-bound proteases and also to free proteases. Quantitative immunochemical levels were about 30-100% of normal plasma levels for alpha-2-macroglobulin, C1 inhibitor, antithrombin III and alpha-2-antiplasmin. However, there was practically no functional inhibitory capacity left in the pseudocyst fluid, except for alpha-1-protease inhibitor, which retained its inhibitory capacity. Neither native kininogen nor complement factor C3 was found: this was probably a result of the proteolytic activity. It is concluded, that a continuing proteolytic activity within the pseudocyst, although decreasing with aging of the cyst, could explain symptoms and complications caused by the pseudocyst.
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PMID:Pancreatic pseudocyst fluid--a mixture of plasma proteins and pancreatic juice possessing a high proteolytic activity. 253 13

The interaction of thrombin, plasmin or their antithrombin III complexes with isolated mouse hepatocytes was studied. Plasmin bound to hepatocytes in a concentration-dependent manner with an apparent Kd of 6.4.10(-8) M, attaining equilibrium within 10 min, and the interaction was inhibited by 6-amino-n-hexanoic acid. Plasmin treated with diisopropylfluorophosphate (DFP) bound to the cells in similar way as the untreated form of the enzyme. Thrombin bound also to hepatocytes, in a concentration-dependent manner, with a Kd of 5.4.10(-8) M reaching a steady state after 180 min. Thrombin inactivated with DFP, however, was inhibited in its binding to these cells. These data suggest that, whereas the kringle domains of plasmin are responsible for the enzyme-cell interaction, the active center of thrombin may be involved in the binding of this enzyme to hepatocytes. Plasmin-antithrombin III and thrombin-antithrombin III complexes were also associated with hepatocytes in a time-dependent manner, reaching a plateau after 180 min, and the two complexes competed in the interaction. While the interaction of active proteinases plasmin or thrombin with hepatocytes did not result in their internalization, the antithrombin III complexes were taken up by the cells, and thrombin-antithrombin III complex was degraded. These results indicate that hepatocytes may participate in the elimination of proteinase-antithrombin III complexes from the plasma, while the association of plasmin and thrombin with hepatocytes could imply distinct biological importance.
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PMID:Association of thrombin, plasmin, thrombin-antithrombin III complex and plasmin-antithrombin III complex with isolated hepatocytes. 254 38

The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10(-5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH.
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PMID:Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm. 257 47

Significance of fibrinolysis in pathophysiology of progressive systemic sclerosis (PSS) has been the subject of much speculation. Renal disease in PSS was associated with significant depression of an inhibitor of fibrinolysis, antithrombin III (ATIII), independent of general disease activity. Association of ATIII depression with plasminogen consumption supports an active role for plasmin or another ATIII-inhibitable enzyme in the pathophysiology of renal disease in PSS, and may explain the thrombotic tendency and propensity for fibrin deposition.
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PMID:Perturbation of fibrinolysis inhibitors in progressive systemic sclerosis. 258 28


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