Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell products contribute to many aspects of the regulation of haemostasis. They include potent inhibitors of platelet aggregation (prostacyclin and nitric oxide) rapidly released in response to agonists such as thrombin. Similar agonists also induce the formation of platelet-activating factor by endothelium. Endothelial cell surface ectonucleotidase enzymes control the catabolism of platelet-active adenine nucleotides. The main source of the circulating coagulant cofactor von Willebrand factor is the endothelium, where it is stored in granules for agonist-triggered exocytosis and also secreted constitutively. Surface anticoagulant activities are due to the presence of antithrombin and thrombomodulin. Endothelial cells also secrete plasminogen activator and its inhibitor. Many of these reactions are significantly modulated by exposure of endothelium to cytokines or bacterial endotoxin, the most striking example being the new synthesis and surface expression of the procoagulant tissue factor (thromboplastin).
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PMID:The control of production and release of haemostatic factors in the endothelial cell. 802 46

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) for other human serine proteases were as follows; thrombin > 2000, trypsin 0.62, chymotrypsin > 2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 microM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.
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PMID:DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa. 802 95

Activated protein C (APC)-protein C inhibitor (PCI) complex and APC-alpha 1antitrypsin (alpha 1AT) complex levels were measured in 29 patients positive for lupus anticoagulant (LA). LA was considered positive if two of the following three criteria were fulfilled: (1) prolongation of the activated partial thromboplastin time, (2) prolongation of the kaolin clotting time (KCT) and KCT mixing test, and (3) prolongation of the dilute Russell's viper venom time (DRVVT) and DRVVT/DRVVT with high lipid concentration. Plasma thrombin-antithrombin III (AT-III) complex and plasmin-alpha 2-antiplasmin inhibitor complex levels in patients positive for LA were increased slightly, but not significantly, and FDP-D-dimer and t-PA levels were not markedly increased. Plasma PAI-1 level in the LA-positive patients was significantly increased compared with normal volunteers. AT-III activity, protein C antigen, PCI antigen, and protein S antigen levels in the LA-positive patients were virtually normal, while protein C activity was slightly, but not significantly, decreased. APC-PCI complex level was increased in all LA-positive patients, and was not detectable in patients with systemic lupus erythematosus and normal volunteers. APC-alpha 1AT complex was increased slightly, in only two LA-positive patients; it was not detectable in the other patients or in the normal volunteers. These findings suggest that patients positive for LA are in a hypercoagulable state and that protein C activity in such patients is decreased, due to the activation of this protein.
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PMID:Increased activated protein C-protein C inhibitor complex level in patients positive for lupus anticoagulant. 805 49

From July 1990 to July 1993, we performed 41 percutaneous intra-arterial thrombolysis procedures for the treatment of obstructed infra-inguinal bypass grafts in 32 patients. There were 27 men and five women with a mean age of 63 +/- 17 years (range 21 to 83 years). The symptoms of occlusion were intermittent claudication in three cases, rest pain in 12 cases, severe ischemia without sensitive-motor loss in 26 cases. Bypasses were achieved using a prosthesis in 18 cases (43.9%), a saphenous vein in 10 cases (24.4%), an arterial allograft in nine cases (21.9%), and a composite prosthesis-vein graft in four cases (9.8%) (table I). The distal anastomosis of the bypass graft was located on the popliteal artery in 26 cases (63.4%) and a crural artery in 15 cases (36.6%). The mean duration of the occlusion was 4.9 +/- 3.4 days (range 1 to 15 days). The percutaneous approach was through the contralateral common femoral artery in 26 cases (63.4%), through the ipsilateral common femoral artery in seven cases (17.1%), through the left humeral artery in eight cases (19.5%). In all cases the thrombolytic agent was the recombinant tissue-type plasminogen activator (rt-PA). Each procedure began with the injection of a five milligram bolus of rt-PA into or onto the thrombus followed by infusion of rt-PA into the thrombus at a dose of 0.05 mg/kg/h. Intravenous heparin was simultaneously administered. Serum fibrinogen, prothrombin time, and partial thromboplastin time (PTT) were measured every three hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intra-arterial thrombolysis using rt-PA for the treatment of occluded infra-inguinal bypasses]. 807 60

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as an extremely potent anticoagulant and reversible tight-binding inhibitor of human factor Xa (FXa). The ecotin gene was cloned by PCR, highly expressed in E. coli, and purified from the E. coli periplasm. The binding of ecotin to FXa was stoichiometric with an equilibrium dissociation constant Ki of 54 pM. The association rate constant was 1.35 x 10(6) M-1 s-1, and the dissociation rate constant, measured in the presence of human leukocyte elastase (HLE) to prevent reassociation of ecotin with FXa, was 6.5 x 10(-5) s-1. Ecotin prolonged clotting time ca. 10-fold at 0.3 microM and at 2 microM in activated partial thromboplastin time and prothrombin time assays, respectively. Ecotin did not effectively inhibit the human plasma proteases thrombin, tissue factor.factor VIIa, factor XIa, activated protein C, plasmin, or tissue plasminogen activator (t-PA); however, it did potently inhibit factor XIIa, plasma kallikrein, HLE, and bovine trypsin and chymotrypsin. Coincubation of ecotin and FXa at 10 microM each resulted in a (ecotin)2.(FXa)2 complex as determined by gel filtration. Dimerization of ecotin alone was measured by fluorescence titration which yielded a Kd of ca. 390 nM. FXa cleaved ecotin slowly at pH 4.0 between M84 and M85. Replacement of the P1 Met84 residue with Arg and Lys led to FXa inhibitors with Ki values of 11 and 21 pM, respectively. The P1 Arg and Lys mutants also significantly inhibited thrombin, factor XIa, activated protein C, plasmin, factor XIIa, kallikrein, and bovine trypsin and chymotrypsin but did not inhibit tissue factor.factor VIIa, t-PA, or HLE.
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PMID:Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor Xa. 814 99

Hemorrhagic events remain the most worrisome complication in patients receiving drugs that alter hemostasis for treatment of acute coronary syndromes. The 7E3 Fab monoclonal antibody provides a dose-dependent inhibition of platelet aggregation via the glycoprotein IIb/IIIa receptor. This study examines the correlation of hemostatic parameters with bleeding events in patients receiving intravenous 7E3 while enrolled in acute myocardial infarction and high-risk percutaneous transluminal coronary angioplasty pilot studies. Patients with acute myocardial infarction received 100 mg of tissue-type plasminogen activator over 3 hours followed by an escalating intravenous bolus dose of murine 7E3 (0.1 mg/kg [n = 5], 0.2 mg/kg [n = 22], 0.15 mg/kg [n = 13], 0.25 mg/kg [n = 20]). Patients in the high-risk angioplasty trial received a chimeric 7E3 bolus (up to 0.25 mg/kg) with (n = 32) or without (n = 15) intravenous continuous infusion of 7E3 (10 micrograms/min for 6 to 24 hours) after elective angioplasty. Patients in both studies received aspirin therapy (325 mg/day) and partial thromboplastin time-guided (1.5 to 2 times normal) heparin infusion. Bleeding events occurred in 34 of 124 patients (27%). The median template bleeding times (minutes) for patients in the groups with bleeding versus no bleeding events in the trials was 13.5 versus 14 and 30 versus 30, respectively (p = NS). In patients with myocardial infarction, a substantial decline in platelet count at 24 hours was associated with bleeding (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of usefulness of prolonged bleeding times in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein IIb/IIIa platelet antibody. The TAMI Study Group. 823 99

Severe thrombotic alterations, such as veno-occlusive disease of the liver, may occur in the early phase following high-dose chemoradiotherapy and BMT. In this study, performed in patients with hematological malignancies subjected to allogeneic (10 cases) and autologous (20 cases) BMT, we have monitored laboratory hemostatic parameters to better understand the pathogenetic mechanism of thrombosis and particularly of veno-occlusive disease. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen, markers of hypercoagulability (thrombin-antithrombin complex and prothrombin fragment F1+2); natural anticoagulants (protein C, protein S and antithrombin) together with fibrinolytic parameters (plasminogen, alpha 2-antiplasmin, tissue-plasminogen activator, plasminogen activator inhibitor and D-dimer) were assessed before transplant, on day 0 and weekly for 1 month thereafter. A hypercoagulability state, not related to an impairment of the anticoagulant and fibrinolytic systems, was documented before and after autologous and allogeneic transplant. Two patients developed veno-occlusive disease: they did not show any difference from the other patients before transplant while they presented a decrease of the natural anticoagulants along with altered fibrinolytic parameters only at the clinical onset of veno-occlusive disease. In conclusion, in this study a state of marked hypercoagulability was documented in BMT patients and the hemostatic laboratory parameters evaluated were not able to predict the occurrence of the thrombotic complications.
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PMID:Hypercoagulability in patients undergoing autologous or allogeneic BMT for hematological malignancies. 824 85

Adjustment in dose based on body size is not recommended currently for thrombolytic regimens, except for a reduction in alteplase (recombinant tissue-type plasminogen activator [rt-PA]) dose for safety reasons in patients with low body weight. It is unresolved how to dose thrombolytic agents in very heavy patients. The study objective was to assess whether patency of the infarct-related artery at 1 day after therapy with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) or rt-PA is adversely affected by increased body weight. Data were analyzed from a double-blind, randomized, comparative study of APSAC (30 U/5 min) versus rt-PA (100 mg/3 hours, adjusted downward for body weight < 65 kg), together with heparin and aspirin, in patients with acute myocardial infarction presenting within 4 hours of symptom onset. Coronary patency, determined at 1 day, was assessed in a blinded fashion, and patency success was correlated with body weight, divided into quintiles. In patients treated with APSAC, coronary patency rates were similar in those in the upper quintile of body weight (> 94 kg; n = 22) and in the low-normal weight group (n = 126) (86 and 90%, respectively, for perfusion grade 2/3 [p = 0.64]; and 82 and 74%, respectively, for grade 3 [p = 0.42]). In contrast, for the rt-PA group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs 89% for grade 2/3 [p = 0.02]; and 59 vs 77% for grade 3 [p = 0.03]). The dose of heparin administered, adjusted to maintain a therapeutic partial thromboplastin time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in the low-normal weight group (mean +/- SE 39,680 +/- 4,818 vs 30,027 +/- 1,177 U; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of reperfusion success with anistreplase or alteplase in acute myocardial infarction to body weight. The TEAM-3 investigators. 827 71

Deinagkistrodon acutus venom contains a collection of anticoagulant proteins that has been reported to prevent prothrombinase assembly (Teng and Seegers, 1981, Thromb. Res. 23, 255). A partial sequence indicates that these proteins are related to the functionally equivalent protein in Trimeresurus flavoviridis (Atoda et al., 1991, J. Biochem. 106, 808). Inhibition of prothrombinase, the complex of Factors Xa and Va combined with phospholipids, is expressed in bovine, human, and rat plasmas as indicated by an assay dependent on only prothrombinase activity. The concentration dependence of inhibition of prothrombin conversion by different combinations of the components of bovine prothrombinase under the same conditions yielded estimates of apparent dissociation constants of 104 nM and 2 nM for complexes of the inhibitor with Factor Xa and with Factors Xa and Va, respectively. Because this inhibitor does not prevent Factor Xa alone from converting prothrombin, but blocks the other combinations, we conclude the inhibitor prevents the complex of Factors Xa and Va from binding to phospholipid surfaces and to prothrombin. The inhibitor also blocks the activation of Factor X by Factor VIIa and thromboplastin as well. However, the inhibitor has no effect on thrombin-induced clotting or fibrinolysis induced by either plasminogen activator or streptokinase. Therefore, this inhibitor has several properties required of an anticoagulant, therapeutic agent.
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PMID:Coagulation factor X inhibitor from hundred-pace snake (Deinagkistrodon acutus) venom. 831 Apr 45

The effects of spa bathing on blood coagulation and fibrinolysis were studied in 20 patients with chronic cerebral infarction. Blood was obtained before and after a 10-minute period of spa bathing at 41 degrees C. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII activity, von Willebrand factor activity, and antithrombin III activity did not show significant changes after bathing, but euglobulin lysis time was significantly reduced (p < 0.01) and fibrin lysis activity was increased (p < 0.05). These findings suggest that spa bathing activates fibrinolysis without markedly changing blood coagulation in patients with chronic cerebral infarction. It is thought that the activation of fibrinolysis without the activation of coagulation has a favorable effect on blood circulation. The results of fibrin-plate assays using C1 inactivator indicated that tissue-type plasminogen activator was the major contributor to the activation of fibrinolysis during spa bathing.
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PMID:Spa bathing activates fibrinolysis in patients with cerebral infarction. 831 58


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