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)

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

Deep vein thrombosis may begin during surgery with the tourniquet inflated. Arterial levels of fibrinopeptide A, thrombin-antithrombin complexes, D-dimer, tissue plasminogen activator (t-PA) activity, and t-PA antigen were measured before surgery, during surgery with the tourniquet inflated, and following deflation of the tourniquet in 12 patients undergoing total knee arthroplasty. Minimal increases in fibrinopeptide A, thrombin-antithrombin complexes, and D-dimer were noted during surgery with the tourniquet inflated, but significant increases occurred immediately following deflation of the tourniquet. In 10 patients, intravenous heparin administration significantly suppressed the rise in fibrinopeptide A, but did not significantly alter the increases in either thrombin-antithrombin complexes, D-dimer, t-PA antigen, or t-PA activity. This study provides further evidence that deep vein thrombosis begins during surgery.
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PMID:Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. 852 13

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

Thrombolytic therapy provides clinical benefit in patients with vascular occlusions, depending upon the organ or limb that is threatened. The impact of therapeutic intervention varies from the quiet alteration of the course of deep vein thrombosis, for which non-life threatening post-phlebitic syndrome can be largely avoided, to the sometimes striking reversal of pulmonary hypertension and possible life-saving benefit in massive pulmonary embolism, the immediate alteration of clinical course in acute peripheral arterial occlusion by reducing the need for surgical intervention, cardiopulmonary complication and one year mortality, and finally to the dramatic and life-saving potential when applied in patients with acute myocardial infarction. Since the risk of serious hemorrhage, especially intracranial hemorrhage, is a constant, regardless of the underlying thrombotic problem, thrombolytic therapy will necessarily be applied variably according to the different potential therapeutic benefits. The balance of potential benefit versus the risk of intracranial hemorrhage in the situation of cerebrovascular thrombosis and stroke remains to be clarified by ongoing studies. As to the evidence for superiority of any single thrombolytic agent or regimen, direct comparative studies are still needed for patients with venous thrombosis and arterial occlusion. Available direct comparisons of two or three agents (streptokinase, urokinase, alteplase and anistreplase) in studies of pulmonary embolism and myocardial infarction show a consistent pattern that documents positive clinical benefit for all of the agents, with striking similarity in quantitative aspects despite marked differences in biochemical properties of the agents.
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PMID:Thrombolytic therapy: overview of results in major vascular occlusions. 857 40

Many reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.), while the patients had significantly lower fibrinolytic activity (p < 0.02), and significantly higher protein concentrations of t-PA (p < 0.0001) and PAI-1 (p < 0.0006). We used probit scale plots to identify the consequence of different cut-off points to separate patients from controls. Reasonable separation could be obtained for t-PA with a cut-off point of 5.2 ng/ml and for PAI-1 18 ng/ml. The sensitivity and specificity for these cut-off points were for t-PA 73% (95% confidence interval 63%-84%) and for PAI-1 67% (confidence interval 55%-77%). The negative predictive value with a cut-off point t-PA concentration of 5.2 ng/ml was 85% (95% confidence interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p < 0.005) and also between PAI-1 and fibrinolytic activity (rs = -0.78; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does low protein concentration of tissue-type plasminogen activator predict a low risk of spontaneous deep vein thrombosis? 858 12

In our experience, severe pulmonary tuberculosis (PTB) is often complicated by deep venous thrombosis (DVT). Because of the association between inflammation and haemostatic changes that can result in a hypercoagulable state, we have prospectively examined such predisposing factors in representative patients. Sequential analyses in a control group with active PTB showed anaemia, thrombocytosis, elevations in plasma fibrinogen, fibrin(ogen) degradation products (FDP), tissue plasminogen activator (t-PA) and inhibitor (PAI-1) with depressed antithrombin III levels. Age, sex and disease matched individuals with venographically proven DVT had higher FDP (15.8 +/- 14.3 v 3.2 +/- 1.7 micrograms/ml:P < 0.01), t-PA (19.4 +/- 14.9 v 11.3 +/- 0.8 ng/ml:P < 0.01), and functional PAI-1 activity (11.6 +/- 6.3 v 4.2 +/- 4.1:P < 0.01) with lower platelet counts (347 +/- 110 v 563 +/- 230 x 10(9)/1:P < 0.01). Fibrinogen levels in all patients rose during the first 2 weeks of therapy and, together with related disturbances, corrected within 12 weeks. In conclusion, elevated plasma fibrinogen with impaired fibrinolysis coupled with a decrease in antithrombin III and reactive thrombocytosis would appear to favour the development of DVT in PTB.
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PMID:Acute-phase response and the hypercoagulable state in pulmonary tuberculosis. 870 31

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24

Hip arthroplasty is associated with a high frequency of postoperative solitary proximal deep vein thrombosis which seems most frequently observed when bone cement is used for prosthesis fixation. Eighteen pigs underwent hemiarthroplasty, eight with cement-fixed prostheses and eight with non-cement prosthesis installation. Levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) activity and plasminogen activator inhibitor 1 (PAI-1) activity were determined in femoral vein blood from both limbs during and after surgery. On the operated side, TAT increased during bone traumatization followed by a substantial rise in t-PA activity and a gradual decline in PAI-1 activity. This indicates a local per- and post-operative sequential activation of coagulation and fibrinolysis followed by a fibrinolytic shutdown, all reflected in femoral vein blood on the operated side. In the animals receiving noncemented hip prostheses, the same pattern of activation of coagulation and fibrinolysis occurred on the operated side. This was, however, less marked than with the cement-fixed prostheses. Postoperative scanning electron microscopic (SEM) examination of the femoral veins showed thrombi on the operated side in 62% of the animals in the cement group and 25% in the non-cement group. In an additional study with eight animals undergoing cement-anchored hip prosthesis operations the levels of TAT, t-PA and PAI-I were analysed in femoral vein blood, mixed venous blood and arterial blood. Significantly higher levels were found in femoral vein blood compared with mixed venous blood while no significant change was found in arterial blood compared with mixed venous blood. The hyperthermia induced by curing bone cement was effectively conducted by the implanted prosthesis and did not seem to exert major influence on the activation of coagulation. Extreme rotation of the limbs during surgery did not in itself induce visible vein wall damage as judged by SEM. These studies indicate that traumatization of bone marrow during hip surgery induce a marked local activation of coagulation and a high incidence of deep vein thrombosis in proximal veins, in particular if bone cement is used for prosthesis fixation.
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PMID:The role of bone traumatization in the initiation of proximal deep vein thrombosis during cemented hip replacement surgery in pigs. 882 20

Thrombolysis today has become a routine option not only in the treatment of acute myocardial infarction but also in many other manifestations of thromboembolic disease. Until one decade ago, only two plasminogen activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and major side effects including systemic fibrinogen breakdown, bleeds and stroke. This has prompted the search for new plasminogen activators with better pharmacological and clinical profiles. The first such new plasminogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasminogen-activator produced by recombinant technology. Both new substances have fueled the development in modern thrombolytic treatment. While the clinical progress with t-PA was confirmed in large, double-blind, randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinase has been substantiated. While the clinical use of t-PA today has been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current research is focused on further plasminogen activators with further improved thrombolytic properties. This review summarizes the current knowledge on the biochemical and pharmacological properties of the first, second and future generation of plasminogen activators.
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PMID:Thrombolytic agents--an overview. 885 12

Thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen-activator (t-PA), plasminogen activator-inhibitor (PAI-1) and quantitative determination of functional protein S (PS) were measured using ELISA procedures in the plasma of 16 untreated patients with newly-diagnosed deep vein thrombosis in the leg and in 10 healthy volunteers. No significant difference in plasma TM, t-PA and PS levels was observed among the controls and patients with deep vein thrombosis. These patients, on the other hand, showed plasma DD, beta-TG and PAI-1 levels significantly higher than the control subjects. These data show that in patients with deep vein thrombosis a hypercoagulable state is a common occurrence.
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PMID:Haemostatic changes in patients with deep vein thrombosis. 917 16


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