Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although thrombolytic therapy is used widely for treatment of acute myocardial infarction (AMI), thrombolysis itself increases thrombin activity and may cause reocclusion of infarct-related vessels. Direct percutaneous transluminal coronary angioplasty (PTCA) is an effective treatment for AMI; however, it is not clear what effects PTCA has on coagulation and fibrinolysis. We investigated coagulation and fibrinolytic factor concentrations before and after direct PTCA. Plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, plasmin-(alpha 2-antiplasmin complex (PAP), tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI)-1 antigen were followed in twelve patients treated with direct PTCA for AMI. Before PTCA, only TAT concentrations were significantly elevated compared to normal controls. D-dimer, TAT, PAP and PAI-1 concentrations were similar before and after PTCA. Eleven patients had no recurrent ischaemia and no restenosis on follow-up coronary angiography. These data confirm that direct PTCA is less likely than thrombolysis to affect coagulation and fibrinolysis.
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PMID:Effects of direct percutaneous transluminal coronary angioplasty treatment of acute myocardial infarction on plasma levels of haemostatic and fibrinolytic factors. 750 63

To determine a possible phase of hypercoagulability after the use of high-dose aprotinin, a prospective randomized double-blind study was performed. Twenty patients undergoing aortocoronary bypass surgery were investigated, a placebo group P (n = 10) was compared to an aprotinin group A (n = 10). Examining parameters of thrombin activation and fibrinolysis, we found during extracorporeal circulation--under continuous aprotinin infusion--a significant inhibition of thrombin activation and fibrinolysis in the aprotinin group (thrombin-antithrombin-III-complexes: 95 +/- 23 micrograms/l, d-dimers: 448 +/- 60 ng/ml, plasminogen activity: 33 +/- 3%, plasminogen activator inhibitor: 98 +/- 14 U/ml) compared to the placebo group (thrombin-antithrombin-III-complexes: 143 +/- 13 micrograms/l, d-dimers: 2755 +/- 430 ng/ml, plasminogen activity: 125 +/- 15%, plasminogen activator inhibitor: 10 +/- 4 U/ml). In contrast, after stopping the aprotinin infusion--from the end of extracorporeal circulation until the morning of the first postoperative day--strong thrombin activation took place in the aprotinin group (d-dimers increased from 472 +/- 90 to 1607 +/- 140 ng/ml), while in the placebo group a decrease could be registered. At this time, the fibrinolysis was still reduced in the aprotinin group (plasminogen activity: 48 +/- 6% vs 85 +/- 16% in the placebo group). In conclusion, interference with the thrombohemorrhagic balance induces hypercoagulability after the use of high-dose aprotinin, with elevated levels of thrombin-antithrombin-III-complexes, d-dimers, and plasminogen and a decreased level of plasminogen activator inhibitor. In our opinion, it is necessary to prevent this counter-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is there a phase of hypercoagulability when aprotinin is used in cardiac surgery? 752 17

Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n = 14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass. Compared with controls, aprotinin reduced blood loss, the number of patients requiring transfusions, and the mean number of transfused red cell units (all with p < 0.05), whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls. Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls (p < 0.05). Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation, without any intergroup differences. The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis, without differences between the groups. The concentrations of D-dimer, a breakdown product of cross-linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may reflect the different modes of action of the two agents, which may make aprotinin more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass.
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PMID:Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. 752 12

Intra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients' plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypofibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy. 753 77

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells. 756 82

We evaluated the mesoglycan effects on the coagulative-fibrinolytic system in 10 patients with euglobulin lysis time (ELT) over 180 minutes. A mathematical model was used to analyze such phenomena. 100 mg of mesoglycan was administered to 10 patients for 14 days. The following parameters were evaluated: tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), euglobulin lysis time (ELT), plasminogen, alpha 2 antiplasmin, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin clotting time (TCT), and fibrinogen. Those parameters were evaluated on the first and on the last day of the mesoglycan treatment at the following times: 0 (basal), 2, 4, 6, 8, 10 and 12 hours. Our results suggest that the mesoglycan is able to reduce a profibrinolytic activity without any influence on the coagulative-fibrinolytic system, at the baseline conditions and after chronic administration. The pharmacodynamic study and the statistical analysis using our mathematic model resulted to be statistically significant.
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PMID:[Effects on the coagulation-fibrinolysis system of a single oral dose of mesoglycan at the beginning and at the end of a prolonged treatment in man]. 756 84

Fibrin deposition is characteristic of inflammatory diseases. The monocytes is central to the inflammatory response and can affect fibrinolysis by expression of urokinase (u-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2, respectively). This study examines whether thrombin, which promotes fibrin deposition, can contribute to fibrin persistence by modulating expression of proteins of the fibrinolytic system. Monocytes were isolated from human peripheral blood and analyzed for PAI-2, PAI-1, and u-PA antigens by enzyme-linked immunosorbent assay (ELISA). Monocytes responded to thrombin by increased expression of PAI-2 in a dose- and time-dependent manner, with maximal synthesis at a concentration of 1 U/mL to 10 U/mL. This trend was also evident for PAI-1, which was present at much lower levels. Thrombin and lipopolysaccharide (LPS) stimulated comparable levels of PAI-2, studied at the antigen and mRNA level. The dose effet of LPS on PAI-2 and PAI-1 was found to differ from that of thrombin. The level of u-PA was undetectable by ELISA and zymography in all samples. Thrombin stimulates PAI-2 synthesis by human monocytes, therefore creating an imbalance in the fibrinolytic system. This may contribute to persistence of fibrin, deposited during inflammation.
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PMID:Thrombin modulates synthesis of plasminogen activator inhibitor type 2 by human peripheral blood monocytes. 757 47

Serine proteinase inhibitors or serpins are a super-family of homologous proteins that are for the most part involved in the regulation of proteolytic processes in a variety of biological systems. Utilizing a polymerase chain reaction-based strategy we have cloned a novel member of the ovalbumin family of serpins from a human bone marrow cDNA library. The new gene encodes a 397-amino acid protein, designated bomapin, with a calculated molecular mass of 45 kDa and 48% amino acid identity with plasminogen activator inhibitor-2, human leukocyte elastase inhibitor, and cytoplasmic antiproteinase. A single 2.3-kilobase bomapin transcript is highly expressed in human bone marrow cells but was undetectable in all other analyzed human tissues. In vitro transcription and translation of the bomapin cDNA revealed the synthesis of an appropriately sized protein that was able to form SDS-stable complexes with thrombin and trypsin. The restricted expression of bomapin to the bone marrow raises the possibility that this serpin may play a role in the regulation of protease activities during hematopoiesis.
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PMID:Molecular cloning of bomapin (protease inhibitor 10), a novel human serpin that is expressed specifically in the bone marrow. 759 9

Seventeen parameters of coagulation and fibrinolysis were measured in 33 patients with sickle cell disease; 30 were tested in steady state (SS) and 19 in crisis (Cr). There were 16 patients in both groups. The same parameters were measured in 16 controls of similar ethnic origin (Black controls; BC) and 20 Caucasian controls (CC), all with HbA only. Highly significant differences (P < 0.001) between Black and Caucasian control groups were noted for: fibrinogen, fibrinopeptide-A (FPA), beta-thromboglobulin (beta TG) and D-dimer. Significant differences (P < 0.03) in plasminogen activator inhibitor (PAI) and functional antithrombin III levels were also noted. Results of the sickle cell patients were therefore compared with those of the Black controls. Sickle cell patients in SS had raised v Wf compared with BC, which increased further during Cr (P = 0.001), but showed no significant increase in fibrinogen. Functional protein C was reduced in SS (P = 0.004) but with no further fall in Cr, while free protein S was normal in SS but reduced in Cr (P = 0.02). Total protein S and ATIII were normal in SS and Cr. FPA and beta TG were not significantly raised in SS or Cr compared with BC. There were, however, highly significant increases in D-dimer and thrombin-antithrombin complexes (TAT) in both SS and Cr compared with BC (P < 0.001 for SS and Cr vs BC). Thus significant activation of coagulation with consequent increase in fibrinolysis occurs during both the sickle cell crisis and in the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in coagulation and fibrinolysis in patients with sickle cell disease compared with healthy black controls. 760 84

Human proteinase inhibitor 6 (PI-6) is a recently described protein belonging to the serine proteinase inhibitor (serpin) superfamily. Sequence similarity suggests that PI-6 most resembles the ovalbumin (ov) serpins which include plasminogen activator inhibitor-2, the squamous cell carcinoma antigen, monocyte/neutrophil elastase inhibitor, and maspin. Although these proteins are associated with carcinomas and inflammation, they appear to have diverse functions and little is known of their physiological roles. In this study we have characterized cDNA and genomic clones encoding mouse PI-6 in order to analyze the localization, structure, and expression of the gene. The reactive center residues (Arg-Cys) are conserved in the mouse molecule, and recombinant mouse PI-6 was shown to bind thrombin, indicating that it has similar inhibitory properties to its human counterpart. Using reverse transcriptase-polymerase chain reaction assays on RNA isolated from 15-day-old embryos and adult mice, we have shown that mouse PI-6 expression is developmentally regulated, and that, unlike human PI-6, it is absent from the placenta. The mouse homologue of the human PI-6 gene has been designated Spi3 and was mapped to chromosome 13 between the Pl1 and ctla2 alpha genes. It spans 20 kilobases, consists of 7 exons and 6 introns, and contains a TATA motif 24 nucleotides upstream of the transcriptional start site. A 680-base pair DNA fragment containing this motif and 31 nucleotides of the 5'-untranslated region of the structural gene directed transcription of a bacterial cat gene, demonstrating the presence of a functional promoter. The PI-6 gene lacks an intron present in the ovalbumin and PAI-2 genes; otherwise it is identical in terms of the numbers, position, and phasing of the intron/exon boundaries. These results suggest that PI-6 and the ov-serpin genes have diverged and do not belong to the same subgroup.
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PMID:Gene structure, chromosomal localization, and expression of the murine homologue of human proteinase inhibitor 6 (PI-6) suggests divergence of PI-6 from the ovalbumin serpins. 760 71


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