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)

In nine patients with non-malignant diseases undergoing major upper abdominal surgery, the mechanism of the postoperative fibrinolytic shut-down was investigated because of its potential significance for postoperative deep vein thrombosis by employing new and specific methods for assessing and stimulating the fibrinolytic system. The shut-down was found to result from an impairment of the balance between tissue-type plasminogen activator, t-PA, and its recently discovered fast-acting inhibitor. In this balance, the t-PA antigen concentrations both in resting conditions and after stimulation evoked by desamino-D-arginine vasopressin (DDAVP) were found to be unchanged by surgery. However, there was a significant postoperative increase in t-PA inhibitor levels. The release of t-PA under the stimulus of DDAVP infusion overcame the postoperative shut-down of t-PA activity. However, DDAVP infusion was associated with potentially unfavourable increases in the Factor VIII/von Willebrand factor complex. The discovery of increased t-PA inhibitor in the postoperative period opens new possibilities for a rational approach to reduce or abolish the postoperative fibrinolytic shut-down.
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PMID:Fibrinolytic shut-down after surgery: impairment of the balance between tissue-type plasminogen activator and its specific inhibitor. 393

Thirty-nine patients with symptomatic, venographically verified deep vein thrombosis (DVT) were studied during treatment with heparin in order to investigate the correlation between the venographic changes and parameters of heparin therapy or fibrinolytic components. Venograms were scored with a 40-grade scale, and after one week a significant improvement with an average reduction of the thrombi of 17% was observed. No statistically significant correlation was found between reduction of thrombus size and duration of heparin treatment, total amount of heparin administered, mean levels of APTT, plasmin-alpha 2-antiplasmin complex (PAP), tissue plasminogen activator (t-PA) antigen or t-PA-inhibitor. Only a short history of the thrombus was significantly correlated to thrombolysis. The concentrations of PAP and t-PA-inhibitor were not influenced, while that of t-PA antigen showed a significant increase during heparin infusion. Even if statistically significant correlations were not obtained, the patients with pronounced thrombolytic effect had high PAP-levels. Furthermore, patients with high t-PA-inhibitor levels had no lysis. The results suggest, that also other factors than plasminogen dependent fibrinolysis are of importance for the thrombolytic effect.
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PMID:Thrombolysis and fibrinolytic parameters during heparin treatment of deep vein thrombosis. 408 3

Rapid inhibition of tissue-type plasminogen activator (t-PA) in human plasma was measured by addition of 5 IU (50 ng) of purified t-PA per ml plasma and measurement of residual t-PA in the euglobulin precipitate after 5 min incubation at 37 degrees C. The recovery of both t-PA activity and t-PA related antigen in pooled plasma from healthy individuals was approximately 90 percent, indicating that one ml of pooled normal plasma inhibits less than 1 IU or 10 ng of t-PA within 5 min. Of 20 control subjects 13 had less than 1 IU inhibitor activity; 5 subjects inhibited between 1 and 3 IU of t-PA and 2 subjects inhibited around 4.5 IU. The inhibitor titer in the latter two had however decreased to 1.8 and 2.7 IU after two days. Markedly increased rapid inhibition of t-PA (greater than 4 IU per ml) was found in plasma of patients with severe liver disease (3 of 8), pancreatitis (4 of 8), malignancy (5 of 26), but only very occasionally and transiently in that of patients with myocardial infarction (5 of 28) or deep vein thrombosis (2 of 9). Increased inhibition was observed on the first day following coronary bypass (22 of 42) or open heart (16 of 27) surgery but this had disappeared in 15 of 16 patients on the fifth postoperative day. Titration of inhibitor levels revealed maximal amounts of 30 to 50 IU per ml plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. 642 82

Fibrinolytic shutdown may be important in the development of postoperative deep vein thrombosis (DVT). We have previously shown that stanozolol 50 mg, given intramuscularly 24 hr before surgery, prevents the decrease in plasminogen activator activity (PA) seen on the first postoperative day in patients at high risk of DVT. To investigate the role of fibrinolytic shutdown in causation of DVT, sixty patients were randomized in a double-blind controlled trial to receive stanozolol or placebo intramuscularly, and DVT was detected by leg scanning and confirmed by venography. Scan positive DVT occurred in 11 of 31 placebo patients (35%) and 12 of 29 who received stanozolol (41%). A significant decrease in PA was confirmed in the placebo group, while stanozolol caused a significant increase in PA on the first postoperative day. Patients in either group who did not develop DVT showed minimal changes in PA. We conclude that prevention of fibrinolytic shutdown by this regimen of stanozolol does not prevent postoperative DVT, and that further studies are required to clarify the relationship of postoperative fibrinolysis and DVT.
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PMID:A double-blind trial of intramuscular stanozolol in the prevention of postoperative deep vein thrombosis following elective abdominal surgery. 653 2

In attempts to determine the aetiology of deep vein thrombosis (DVT) it has been established that some patients with a history of lower limb DVT have a low level of vascular plasminogen activator (VPA) in their superficial hand veins and this combined with a poor VPA release is thought to predispose to thrombosis (1). Hand veins rarely develop thrombosis and so the level of VPA has been measured quantitatively in the more commonly at risk veins of the lower limb. In 6 limbs operated on for varicose veins, paired samples of vein from the groin and from the calf were examined. The median activity score for the groin veins (8138 cpm/micrograms) was significantly higher than the activity in the calf veins (2353 cm/micrograms)(P = 0.01). In 9 limbs amputated for critical ischaemia, paired samples of calf long saphenous vein and soleal vein were examined. The VPA in the former was 1675 cpm/micrograms compared with 6796 cpm/micrograms in the soleal veins. This difference is significant at the 1 per cent level. A correlation has been shown between the VPA content of these two sets of veins (R = 0.87). The low level of VPA in the superficial calf veins may be an aetiological factor in superficial thrombophlebitis, but the commonest site for DVT, the soleal veins of the calf, have a high level of VPA.
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PMID:Vascular plasminogen activator and deep vein thrombosis. 668 16

Forty-five patients with ischemic cerebrovascular disease (ICD) and 44 with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) have been investigated in a non-active state of the disease with VIIIR:Ag, plasminogen activator before and after stasis, antiplasmin, antithrombin (activity, antigen, activity/antigen ratio) and spontaneous platelet aggregation. Control groups of 20 respectively 80 healthy females and males were used in the study. VIIR:Ag was elevated in the group with deep venous thromboembolic disease compared with the ICD group and a control group. VIIIR:Ag in the ICD group was elevated compared with the control group. Plasminogen activator determined before and after stasis was lowered in the two diseased groups. There was no statistically significant difference in any of the blood coagulation variables between patients on or off coumarol treatment. The patients on courmarol were, however, not reinvestigated when this medication had been withdrawn. Antithrombin levels below the reference interval of the control group of 80 blood donors were found in 11.4% of the patients with DVT/PE, whiel no patient in the ICD group had low antithrombin values.
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PMID:Blood coagulation studies in 45 patients with ischemic cerebrovascular disease and 44 patients with venous thromboembolic disease. 677 May 84

Intermittent pneumatic compression (IPC) or graduated static compression stockings, both effective mechanical methods in the prophylaxis of postoperative deep venous thrombosis, have been investigated in 50 patients regarding the effect of compression on the fibrinolytic system and factor VIII activators. All the patients were subjected to one of the two methods before operation upon varicose veins. In 38 patients IPC with a pressure of 40 mmHg was applied on one leg or arm for at least two hours. In 23 of these patients the compression pattern was slow, two minutes' inflation and two minutes' deflation period. In the remaining 15 patients the compression pattern was quick, three seconds' inflation, followed by 20 seconds' deflation, three cycles a minute. Twelve patients were treated with a compression stocking on one leg for about 24 hours before the operation. Blood samples for determination of fibrinolytic activity and factor VIII in plasma were obtained before and immediately after the end of compression and application of a stocking, respectively. Also the level of plasminogen activator activity (PA) in the vein wall was determined. Neither IPC nor the application of an elastic stocking had any demonstrable effect on the variables studied. In addition, the results did not vary with the rate (slow or quick) or with the duration of IPC, sex or site of application (arm or leg) of IPC. Blood samples from the compressed leg were also uninfluenced.
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PMID:Effect of intermittent pneumatic and graduated static compression on factor VIII and the fibrinolytic system. 680 41

These studies describe an assay of whole blood clot lysis as measured by release of 125I-fibrinogen degradation products. Optimal rates of lysis were obtained at 37 degrees C in 10-12 mM EDTA or 3,8% citrate and 4 u of thrombin/ml. Eighteen normal subjects and eight patients (six with recurrent deep vein thrombosis, one with thrombasthenia, and one with hepatitis and resolving portal vein thrombosis) were studied using this assay. The clots of seventeen of the eighteen normal subjects were 50% lysed at 40 hours. The clots of the patients with venous thrombosis and thrombasthenia did not lyse whereas the clots of the patient with hepatitis, resolving portal vein thrombosis and a high plasminogen activator level (0.32 CTA units) were 100% lysed at 4.5 hrs.
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PMID:Observations on optimal conditions for lysis of whole blood clots and use of this assay as a screening assay in clinical investigation. 682 Jan 94

Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase-human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases, with a catalytic mechanism which operates via acyl-enzyme intermediates. Chase and Shaw showed that p-nitrophenyl-p'-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase-plasmin(ogen) complexes.
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PMID:Fibrinolysis with acyl-enzymes: a new approach to thrombolytic therapy. 721 37

Thrombolytic therapy mimics and enhances physiological fibrinolysis. The following substances are presently available for clinical use: the nonphysiological thrombolytics streptokinase, the APSAC (acylated plasminogen-streptokinase activator complex), the physiological plasminogen activators urokinase and tissue plasminogen activator (t-PA). Whereas the first three systematically activate the fibrinolytic system, t-PA possesses relative fibrin selectivity. The fibrin-selective active pro-urokinase has not yet been officially approved for the treatment of thromboembolic diseases, but it is being clinically tested. Fibrinolytic therapy has an established place in the management of acute myocardial infarction and of massive pulmonary embolism. When an acute deep venous thrombosis is diagnosed with a proximal extension into the popliteal vein, thrombolytic therapy is clearly superior to heparin. The lysis has proven to be an effective form of treatment of peripheral occlusive arterial disease. Local thrombolytic therapy is an option for acute and chronic femoro-popliteal occlusions involving the trifurcation into the calf arteries and for embolic occlusions of the same segment in patients with contraindications to surgical therapy. First study results of thrombolytic therapy of stroke are promising.
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PMID:[Fibrinolytic agents--who benefits when?]. 748 76


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