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)

In 14 consecutive patients undergoing cardiopulmonary bypass for coronary bypass surgery the time course of coagulation and fibrinolysis markers were measured, e. g. plasma levels of thrombin-antithrombin III (TAT) complexes, cross-linked fibrin degradation products (XIFDP) and plasmin-alpha 2-antiplasmin complexes (PAP). TAT levels exceeded the 90% baseline percentile already during CPB (after opening of aortic clamp) in 10 patients, whereas PAP and XIFDP exceeded their 90% percentile in only one patient at this time. Concerning fibrinolysis markers PAP and XIFDP the majority of patients showed elevations higher than their 90% baseline percentile only 1 h postoperation. Correlation analysis revealed significant dependencies between TAT levels during and at the end of CPB and PAP levels 1 h postoperation (R = 0.55 and R = 0.56 respectively). Furthermore, 1 h postoperation XIFDP levels were significantly correlated with both TAT and PAP. Peak XIFDP levels at the same time correlated with blood loss via thoracic drains (R = 0.56). Thus, we suggest that hyperfibrinolysis in patients undergoing CPB is at least partly due to hypercoagulation. Clinically, this may implicate that intensified anticoagulation could prevent hyperfibrinolysis and reduce postoperative blood loss.
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PMID:Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis. 144 Apr 86

Thrombin activatable fibrinolysis inhibitor (TAFI) also named procarboxypeptidase U (CPU), procarboxypeptidase R (CPR) and plasma procarboxypeptidase B (CPB) provides an important link between fibrinolysis and coagulation cascade. Activated TAFI (TAFIa) reduces a generation of plasmin because it cleaves off the carboxy-terminal lysine residues from partially degraded fibrin and thereby abrogates the fibrin cofactor function in the tPA-mediated catalysis of plasminogen to plasmin. TAFI is activated by thrombin-thrombomodulin complex. TAFI transformation to the activated TAFI (TAFIa) induced by thrombin supports the important role of coagulation cascade in regulation of fibrinolysis. This can be proved by a fact that the patients with a factor XI (FXI) deficiency are prone to bleeding from tissues with a high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) that can be explained by a decreased thrombin-mediated TAFI activation. On the other hand the prothrombotic mutation of factor V (FV Leiden) associated with a resistance to activated protein C (APC-resistance) possess both mechanisms-an increased thrombin generation in coagulation cascade and a down regulation of fibrinolysis by a way of the thrombin-induced TAFI activation. For the future an inhibition of TAFI (e.g. by FXI inhibitors) offers the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders. In bleeding disorders (hemophilia A, B) the drugs with a higher efficiency of TAFI for down regulation of an increased fibrinolysis could be used.
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PMID:[Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis]. 1501 28

Coagulation and fibrinolysis system was evaluated during and after pediatric cardiopulmonary bypass (CPB. Twenty-two atrial septal defect (ASD) patients were surgically repaired under CPB and aortic cross-clamp through right thoracotomy. Drainage was established by gravity, CPB flow was kept 2.4 l/min/m2 and ACT was controlled over 400 seconds. HCT, PLT, fibrinogen, AT-III, D-dimer, thrombin-antithrombin complex (TAT), alpha2 plasmin inhibitor-plasmin complex (PIC), and plasminogen activator inhibitor (PAI-1) were measured at 6 points [after induction of anesthesia, 10 minutes after initiating CPB, end of CPB, on the entrance of intensive care unit (ICU), postoperative day (POD) 1, and at outpatient division]. Both fibrinogen and AT-III showed low values during CPB (121.9 +/- 22.0 mg/dl, 57.6 +/- 10.6%). D-dimer increased at 1 week postoperatively in all patients (5.57 +/- 3.45 microg/ml). There were significantly positive correlations between CPB duration and TAT value at the end of CPB (r = 0.88, p < 0.01), on the entrance of ICU (r = 0.71, p < 0.01). There was also a positive correlation between CPB duration and PIC value on the entrance of ICU (r = 0.53, p < 0.01). Five patients showed high PAI-1 value on the entrance of ICU, which remained high in 2 of them on POD 1. The outcomes from the current study suggest that there is a potential of coagulation-dominant disseminated intravascular coagulation (DIC) during pediatric CPB even in ASD patients who do not need long CPB. Longer CPB and severe hemodilution might become risk factors.
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PMID:[Coagulation and fibrinolysis system in pediatric cardiopulmonary bypass]. 1716 8

Chemerin is a potent chemoattractant for cells expressing the serpentine receptor CMKLR1 (chemokine-like receptor 1), such as plasmacytoid dendritic cells and tissue macrophages. The bioactivity of chemerin is post-translationally regulated; the attractant circulates in blood in a relatively inactive form (prochemerin) and is activated by carboxyl-terminal proteolytic cleavage. We discovered that plasma carboxypeptidase N (CPN) and B (CPB or activated thrombin-activable fibrinolysis inhibitor, TAFIa) enhanced the bioactivity of 10-mer chemerin peptide NH(2)-YFPGQFAFSK-COOH by removing the carboxyl-terminal lysine (K). Sequential cleavages of either a prochemerin peptide (NH(2)-YFPGQFAFSKALPRS-COOH) or recombinant full-length prochemerin by plasmin and CPN/CPB substantially increased their chemotactic activities. Endogenous CPN present in circulating plasma enhanced the activity of plasmin-cleaved prochemerin. In addition, we discovered that platelets store chemerin protein and release it upon stimulation. Thus circulating CPN/CPB and platelets may potentially contribute to regulating the bioactivity of leukocyte chemoattractant chemerin, and further extend the molecular link between blood coagulation/fibrinolysis and CMKLR1-mediated immune responses.
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PMID:Regulation of chemerin bioactivity by plasma carboxypeptidase N, carboxypeptidase B (activated thrombin-activable fibrinolysis inhibitor), and platelets. 1901 Jul 84