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)

Measurement of fibrinogen-fibrin degradation products (FDP) levels in plasma may provide a direct index of plasmin action, and increased levels of FDP would indicate coagulopathy. We have established an E-neoantigen radioimmunoassay ( Eneo RIA) that can determine normal and pathological plasma levels of E-related FDP. The assay employs rabbit antiserum produced against fragment E derived from a plasmin digest of fibrinogen and subsequently absorbed with fibrinogen. The absorbed antiserum contains antibodies which are equally reactive with fibrinogen derived E (Fg-E) and fibrin derived E (Fb-E) but not with fibrinogen at 1 mg/ml. The Eneo RIA was validated by assay parallelism and by recovery experiments. Plasma Eneo immunoreactivities in 14 normals were 4-22 ng/ml (mean 12.7 ng/ml). Plasma Eneo levels in 23 of 24 patients with neoplastic and haematological diseases were elevated above normal (range 27-2027 ng/ml). Unusually high Eneo values were observed with three patients whose diseases were complicated by either disseminated intravascular coagulation (DIC) or deep vein thrombosis. After heparin therapy, the Eneo level of a patient with chronic DIC declined. A pathological plasma was eluted from a Sephadex G-200 column and Eneo immunoreactivity was determined on the eluates. The gel filtration pattern of Eneo indicates that E-related FDP is a family of plasmic fragments derived from crosslinked fibrin.
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PMID:Radioimmunoassay of fragment E-related neoantigen: validation studies and clinical application. 672 32

Streptokinase and urokinase are the two thrombolytic agents currently available in the United States. These drugs promote dissolution of thrombi by stimulating the conversion of plasminogen to plasmin, resulting in an overall "lytic state" in the blood. Recent clinical trials in patients with pulmonary emboli, deep vein thrombosis, arterial thrombosis, and arteriovenous cannula occlusions demonstrated significantly greater lysis with thrombolytics than with heparin alone. However, because of the increased risk of bleeding, the use of these agents is reserved for patients in whom the therapeutic advantages outweigh the disadvantages. Contraindications are numerous and include any preexisting condition that may render the patient more susceptible to bleeding.
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PMID:Advances in thrombolytic therapy. 704 63

Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase-human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases, with a catalytic mechanism which operates via acyl-enzyme intermediates. Chase and Shaw showed that p-nitrophenyl-p'-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase-plasmin(ogen) complexes.
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PMID:Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy. 721 37

Alteplase is the product of recombinant DNA technology and is chemically identical to endogenous tissue-type plasminogen activator: Plasminogen is converted to plasmin by alteplase, and fibrinolysis of blood thrombi is subsequently stimulated. Alteplase is now firmly established as a treatment of choice in the management of acute myocardial infarction. The efficacy of intravenous alteplase in the treatment of pulmonary thromboembolism has also been established and appears to be similar to that of streptokinase and urokinase in this indication and in arterial thrombotic occlusion. However, its use in this latter indication and in other vascular disorders has not been as extensively documented. Although trials demonstrating the efficacy of intravenous alteplase in patients with deep vein thrombosis and intra-arterial alteplase in patients with arterial thrombotic occlusion exist, reliable data on the efficacy of the fibrinolytic in ischaemic stroke and intracranial haemorrhage are scarce. Little clinical benefit is apparent in patients with unstable angina, although careful use may be warranted in those with definite pretreatment coronary thrombi. Of concern, there is a suggestion that general use of alteplase in patients with unstable angina may be associated with increased incidence of myocardial infarction. The incidence of major haemorrhage associated with alteplase therapy increases with increasing dose and appears to be similar to that seen with other fibrinolytic agents. Thus, further well-designed studies of the use of alteplase in ischaemic stroke and cerebral haemorrhage are required. However, a small subset of patients with unstable angina and definite pretreatment coronary thrombi may benefit from alteplase therapy. Further, preliminary data suggest efficacy in the therapy of deep vein thrombosis and arterial thrombotic occlusion, and alteplase has a proven place in the fibrinolytic treatment of pulmonary thromboembolism.
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PMID:Alteplase. A reappraisal of its pharmacology and therapeutic use in vascular disorders other than acute myocardial infarction. 852 60

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.
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PMID:Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis. 856 33

We examined hemostatic abnormalities in 23 patients with acute myocardial infarction (AMI), 10 with pulmonary embolism (PE), and 10 with deep vein thrombosis (DVT). At the onset of AMI, plasma levels of tissue-type plasminogen activator (t-PA), PA inhibitor-I (PAI-I), fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased. Both the plasma total TFPI and free-TFPI levels in the AMI patients were significantly higher than those in the healthy volunteers, PE patients, and DVT patients. There was no significant difference in total TFPI or free-TFPI among patients with PE, those with DVT, and healthy volunteers. One hour after percutaneous transluminal coronary angioplasty (PTCA) in the AMI group, the total TFPI level was further increased, and it was significantly reduced 24 hr after PTCA, to a level similar to that in healthy volunteers. Free-TFPI showed a pattern similar to that of total TFPI. The ratio of free-TFPI/total TFPI was highest 1 hr after PTCA. Increased TFPI in AMI patients might be released from ischemic tissues.
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PMID:Increased tissue factor pathway inhibitor in patients with acute myocardial infarction. 925 77

Extradural anaesthesia is associated with lower incidences of deep vein thrombosis after total knee arthroplasty. It is not known if the type of anaesthesia influences thrombogenesis or fibrinolysis during knee surgery performed under tourniquet. We studied 31 patients allocated randomly to receive either extradural or general anaesthesia for primary unilateral total knee arthroplasty performed under tourniquet. Radial artery blood samples were obtained before surgery, during surgery with the tourniquet inflated and on deflation of the tourniquet. Plasma samples were assayed for markers of thrombin generation and fibrinolysis. Two of the circulating indices of thrombin generation, fibrinopeptide A and thrombin-antithrombin complexes, increased to a similar degree in the perioperative period in both groups. Fibrinolytic activity was similar in both groups, as measured by tissue plasminogen activator (t-PA) antigen, t-PA activity, t-PA-plasminogen activator inhibitor complexes, alpha 2-plasmin inhibitor-plasmin complexes and D-dimer. Extradural and general anaesthesia did not result in significant differences in either thrombin generation or fibrinolytic activity during total knee arthroplasty performed under tourniquet.
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PMID:Comparison of extradural and general anaesthesia on the fibrinolytic response to total knee arthroplasty. 950 95

Without prophylaxis, patients subjected to major abdominal surgery have a risk of deep vein thrombosis of approximately 30%, while the rate varies between 40% and 60% in orthopedic surgery. The reasons for this discrepancy are not completely understood. The present study was designed to compare the pre- and postoperative behavior of different coagulation and fibrinolysis parameters in patients undergoing both types of surgery, receiving low molecular weight heparin prophylaxis. Samples were taken before operation and on postoperative days 1, 3, and 7. The following parameters were assessed: prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinopeptide A, tissue plasminogen activator, plasminogen activator inhibitor, plasmin-alpha 2-antiplasmin complexes, and fibrin degradation products. We found a significant increase in the clotting markers postoperatively compared with preoperative values (P < 0.05), both in abdominal and orthopedic surgery, indicating a marked hemostatic activation which remained until postoperative day 7. A significant increase in plasminogen activator inhibitor (P < 0.01) and a decrease in tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes was also observed early after operation. The plasminogen activator inhibitor activity decreased, while tissue plasminogen activator and plasmin-alpha 2-antiplasmin levels increased significantly on days 3 and 7 (P < 0.05). Fibrin degradation products significantly increased throughout the postoperative period (P < 0.01). Preoperatively, we found higher plasminogen activator inhibitor activity and lower tissue plasminogen activator and plasmin-alpha 2-antiplasmin complexes (P < 0.05) in patients undergoing hip replacement compared with abdominal surgery. Fibrin degradation products were also significantly lower on postoperative day 3 in patients undergoing hip replacement (P < 0.01). We suggest that the lower preoperative fibrinolytic activation observed in patients undergoing orthopedic surgery compared with abdominal surgery might have pathophysiological consequences. Our results also indicate that the hemostatic activation persists beyond the 7th postoperative day despite prophylaxis.
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PMID:Hemostatic markers in surgery: a different fibrinolytic activity may be of pathophysiological significance in orthopedic versus abdominal surgery. 950 66

Cleavage of crosslinked fibrin by the fibrinolytic enzyme plasmin leads to the formation of fibrin degradation products, among them D-dimers. D-Dimer can easily be measured in plasma or in whole blood by means of monoclonal antibodies directed against epitopes of the D-dimer fragment. Elevated plasma levels of D-dimers are characteristic for patients with venous thromboembolism (DVT, PE), but occur also in patients with infectious diseases, malignant neoplasms and heart failure. Given the high sensitivity of ELISA D-dimer assays with respect to venous thromboembolism it is possible to reliably rule out DVT or PE when the plasma concentration of D-dimer is below the cut-off level. Thus, it is possible to rule out DVT in about 30% of outpatients with suspected venous thromboembolism by the measurement of D-dimer-concentration with a validated assay avoiding further diagnostic procedures.
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PMID:[D-dimer determination in suspected deep venous thrombosis or lung embolism]. 1051 27

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


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