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)

Increases in thrombin activity in patients given fibrinolytic agents for acute myocardial infarction have been shown to be important in limiting the ultimate success of coronary thrombolysis. The present study was designed to determine whether increases in thrombin activity reflect, in part, activation of prothrombin accompanying thrombolysis. Plasma concentrations of prothrombin fragment 1.2, a polypeptide released when prothrombin is activated by factor Xa, were measured in 22 patients with acute myocardial infarction before and after treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA). Concentrations of prothrombin fragment 1.2 increased from 0.83 +/- 1.1 nM (mean +/- SD) before rt-PA infusion to 1.5 +/- 1.5 nM 2 h after initiation of the infusion (p less than 0.05). After a 5,000-U intravenous dose of heparin given at the end of the infusion of rt-PA, concentrations of prothrombin fragment 1.2 decreased from 1.8 +/- 1.5 to 1.1 +/- 0.9 nM (n = 20, p less than 0.05), although values were still increased compared with concentrations before rt-PA. These results indicate that thrombin activity increases in patients given rt-PA at least in part because of activation of the coagulation system leading to activation of prothrombin. Thus, inhibition of the reactions involving coagulant proteins that lead to activation of prothrombin may be of value as conjunctive treatment to potentiate the efficacy of pharmacologic thrombolysis.
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PMID:Activation of prothrombin accompanying thrombolysis with recombinant tissue-type plasminogen activator. 155 97

Thrombolytic therapy is rarely used in venous thromboembolism because of the fear of hemorrhagic complications. Preliminary clinical experiences with recombinant tissue-type plasminogen activator (rt-PA) in patients with deep vein thrombosis have shown that even this fibrin-specific plasminogen activator causes an unacceptable rate of hemorrhagic complications. Theoretical considerations and the available experimental and clinical data suggest that infusion of rt-PA over a short period of time would result in a more favorable risk-benefit ratio. Shortening the period of rt-PA infusion results in higher peak plasma levels, thus allowing a higher concentration of the plasminogen activator on the surface and inside the occluding thrombus. In addition, a bolus infusion can prevent or minimize the interaction between rt-PA and the hemostatic system, reducing the likelihood of a systemic lytic state, of a platelet function defect, and, possibly, of bleeding side effects. In venous thromboembolism animal models, the efficacy of bolus rt-PA can be further increased by the adjunctive administration of an effective antithrombotic treatment. This is because the accretion of new fibrin on the thrombi counteracts the lysis of preformed fibrin and influences negatively the final thrombus size. Effective adjunctive antithrombotic treatment includes either high doses of heparin, producing an unclottable activated partial thromboplastin time (aPTT), or doses of recombinant hirudin, doubling the aPTT. When used as an alternative to rt-PA, bolus doses of a hybrid plasminogen activator with prolonged half-life efficiently reduce thrombus size by lysing preformed and newly formed fibrin. Preliminary clinical experience in patients with pulmonary embolism seems to confirm that rt-PA infused as a bolus is at least as effective as, and probably more effective than, rt-PA infused over a longer period.
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PMID:Bolus thrombolysis in venous thromboembolism. 155 82

Antistasin is a 119-amino acid protein initially isolated from salivary glands of the Mexican leech, Haementeria officinalis, that exhibits potent anticoagulant properties resulting from selective inhibition of blood coagulation factor Xa. The comparative antithrombotic efficacies of recombinant antistasin (rATS), standard heparin (Hep), and aspirin (ASA) administered adjunctly with recombinant tissue-type plasminogen activator (tPA) on thrombolytic reperfusion and reocclusion were determined in a canine model of femoral arterial thrombosis. An occlusive thrombus was formed by insertion of a thrombogenic copper coil into the femoral artery, and blood flow velocity was monitored directly and continuously by Doppler flowmetry. Sixty minutes after occlusion, dogs received an intravenous infusion of either saline (vehicle) or rATS (0.31, 1.25, or 2.5 micrograms/kg/min), intravenous boluses of Hep (100 units/kg + 50 units/kg/hr or 200 units/kg + 150 units/kg/hr), or a single intravenous bolus of ASA (2.0 mg/kg), followed 45 minutes later by tPA (0.8 mg/kg i.v. over 90 minutes). The saline and rATS infusions were discontinued 60 minutes after termination of tPA, and the last Hep boluses were given 105 minutes after termination of tPA. All dogs achieved reperfusion. The time to reperfusion in the ASA group was similar to that in the vehicle group (50 +/- 9 versus 50 +/- 6 minutes, respectively). Reperfusion times were slightly decreased by the low and high doses of Hep (34 +/- 6 and 31 +/- 4 minutes, respectively) and the rATS doses of 0.31 and 1.25 micrograms/kg/min (37 +/- 4 and 36 +/- 5 minutes, respectively). However, the time to reperfusion was dramatically reduced with the 2.5 micrograms/kg/min rATS dose (15 +/- 3 minutes, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acceleration of recombinant tissue-type plasminogen activator-induced reperfusion and prevention of reocclusion by recombinant antistasin, a selective factor Xa inhibitor, in a canine model of femoral arterial thrombosis. 157 36

Having previously shown in the Heparin Aspirin Reperfusion Trial that the empiric use of early intravenous heparin after recombinant tissue-type plasminogen activator (rt-PA) is an important component in the overall treatment strategy, we examine in this report the specific relation between the degree of prolongation of activated partial thromboplastin time and coronary artery patency. To evaluate the hypothesis that arterial patency after administration of rt-PA for acute myocardial infarction is sustained by effective anticoagulation, activated partial thromboplastin time of heparin recipients was determined 8 and 12 h after the start of thrombolysis. Mean activated partial thromboplastin time was higher among patients with an open infarct-related artery than in those with a closed artery (81 +/- 4 vs. 54 +/- 9 s, p less than 0.02). Only 45% of patients with values less than 45 s at both 8 and 12 h had Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 in the infarct-related artery at 18 h. In contrast, 88% of patients with activated partial thromboplastin time greater than 45 s and 95% of those with values greater than 60 s had an open infarct-related artery at 18 h (p = 0.003 and 0.0006, respectively). Among patients with an initially patent infarct-related artery who underwent repeat angiography at 7 days, activated partial thromboplastin time was similar in those with a persistently patent artery and those with late reocclusion. Excessive anticoagulation did not appear to increase hemorrhagic risk except that access site-related hemorrhage was more common in patients with activated partial thromboplastin time greater than 100 s at 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin-induced prolongation of partial thromboplastin time after thrombolysis: relation to coronary artery patency. HART Investigators. 160 35

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.
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PMID:Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction. 162 56

The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5-70 years) were collected within the first 36 hours and at 5-7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): less than 20%, n = 22; 20%-40%, n = 18; greater than 40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Plg), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1Inh), and factor VII clotting and antigen (FVII:c, FVII:ag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT increases) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di increases) occurs via an increase in tPA with a p value increase in PAI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state. 163 6

Venous thromboembolism is complex with a multifactorial etiology. The Virchow triad (changes in blood flow, changes in vessel wall, and changes in the properties of blood) gives the main factors involved in venous thromboembolism. Venous stasis during immobilization in general anesthesia, stroke with hemiparesis, and heart failure plays a central role. The thromboembolic process can be initiated by a disturbance in the normal "hemostatic balance," with an increased thrombogenic potential, due to release of thromboplastin and collagen exposure during vessel wall injury by stasis and hypoxia, decreased fibrinolysis during surgery, malignancy, among others. Many substances modify these processes, including heparan sulfate, AT III, protein C, t-PA inhibitor, and alpha 2-antiplasmin.
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PMID:Pathophysiology of venous thromboembolism. 175 82

Activation and inhibition of the haemostatic system was reviewed including the interaction between the four biological systems involved in haemostasis: the vessel wall, the platelets, the coagulation system and the fibrinolytic system. The haemostatic mechanism is initiated at the site of injury through local activation of surfaces and release of tissue thromboplastin, resulting in formation and deposition of fibrin. The coagulation process is regulated by physiological anticoagulants. Activation of fibrinolysis is triggered by the presence of fibrin, and the role of tissue-type plasminogen activators (t-PA) at the site of fibrin formation in particular is emphasized. The process is regulated by physiological inhibitors, of which alpha 2-antiplasmin, histidine-rich glycoprotein and plasminogen activator inhibitor are reported to be of major physiological significance. The role of fibrinolysis in the regulation of the dynamic haemostatic balance is discussed, elucidated through examples of congenital deficiencies of the coagulation and the fibrinoytic system. Pharmacological inhibitors of fibrinolysis (i.e. epsilon-aminocaproic acid and tranexamic acid) and their possible effect on the haemostatic system are described. The systemic effects on the fibrinolytic system of surgery and oral surgery is reviewed, and it is concluded, that oral surgery has insignificant effects on blood fibrinolysis. In contrast, oral surgery induces changes of fibrinolysis in the oral environment; initially the fibrinolytic activity of saliva is reduced, due to the presence of inhibitors of fibrinolysis originating from the blood and the wound exudate. When bleeding and exudation cease, the fibrinolytic activity of the saliva will increase. Plasminogen and plasminogen activator, identified as t-PA are present in the oral environment under physiological conditions. Plasminogen is secreted in the saliva and the sources of t-PA include oral epithelial cells and gingival crevicular fluid. The presence of plasminogen and t-PA in the oral environment implies that when fibrin is present (i.e. after surgery), fibrinolysis is triggered. Haemorrhagic complications to oral surgery in patients without known defects of the coagulation system is reviewed. It is concluded that the investigations conducted to the present day do not permit final conclusions with respect to the pathophysiological role of defects in the coagulation and the fibrinolytic systems for the development of bleeding after oral surgery. Further investigations are necessary in order to clarify these aspects, and should include extensive laboratory analyses to reveal rare congenital defects such as factor XIII- and alpha 2-antiplasmin deficiencies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Haemostasis in oral surgery--the possible pathogenetic implications of oral fibrinolysis on bleeding. Experimental and clinical studies of the haemostatic balance in the oral cavity, with particular reference to patients with acquired and congenital defects of the coagulation system. 180 33

The effect of recombinant hirudin (r-hirudin, LU 52369) and unfractionated heparin on recombinant tissue-type plasminogen activator (rt-PA; LU 50232) thrombolysis and reocclusion rates after successful thrombolysis was studied in a copper-coil-induced thrombus model in the iliac artery of anesthetized rabbits. Simultaneous administration of rt-PA and recombinant hirudin (r-hirudin) at a dose not affecting the partial thromboplastin time (PTT) increased the number of recanalized arteries significantly. The incidence of reocclusion was drastically reduced from 100% to less than 25%. At a dose increasing PTT twofold, unfractionated heparin had no effect on the incidence of reperfusion and reocclusion. These experimental data indicate that the combination of rt-PA with low-dose r-hirudin may be useful for the prevention of early reocclusion in thrombolytic therapy.
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PMID:Effect of recombinant hirudin (LU 52369) on reocclusion rates after thrombolysis in rabbits. 189

Development of thromboplastin (tpl) and plasminogen activator (PA) activity in monocytes and the effects of high doses of corticosteroids (HCD) on these activities were studied in patients undergoing a standardized surgical trauma. Twelve patients who received uncemented total hip prostheses were divided into a nonsteroid group (n = 6) and a steroid group (n = 6). We found no significant differences between the two patient groups regarding tpl or PA activities of peripheral blood mononuclear cells (PBM) isolated during the postoperative phase. However, in the nonsteroid group there was a tendency for increased expression of procoagulant activity and decreased fibrinolytic activity on the 1st postoperative day, favoring the formation of fibrin in the monocyte microenvironment. Further, PBM isolated on the 1st and 2nd day after surgery were significantly less capable of generating tpl activity on endotoxin stimulation than cells isolated preoperatively. This was not the case in the steroid group. These patients had also a tendency for decreased fibrinolysis at the end of the 1st postoperative week, indicating increased imbalance towards a more thrombotic stage after surgery.
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PMID:Generation of procoagulant (thromboplastin) and plasminogen activator activities in peripheral blood monocytes after total hip replacement surgery. Effects of high doses of corticosteroids. 189 63


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