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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
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PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38

The plasma concentrations of tissue plasminogen activator (t-PA) antigen, cortisol, testosterone, dehydroepiandrosterone sulphate, FSH and LH were studied in 33 men undergoing major abdominal surgery. Significant positive correlation was found between the concentrations of t-PA antigen and cortisol, suggesting that the adrenal cortex has a role in the regulation of extrinsic fibrinolysis. These two variables, however, did not distinguish between patients with postoperative deep vein thrombosis (diagnosed by 125I-fibrinogen uptake test) and those without this complication. Such distinction was possible, however, with another steroid hormone of the adrenal cortex, dehydroepiandrosterone sulphate. At present, no explanation in terms of haemostatic mechanisms can be offered for this finding.
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PMID:Relationships between tissue plasminogen activator, steroid hormones and deep vein thrombosis. 293 51

Using affinity chromatography on lysine Sepharose 4B, a fast-acting tissue plasminogen activator inhibitor (t-PAI) was partially purified from t-PAI-rich plasma from patients with recurrent DVT. Its inhibition of tissue plasminogen activator (t-PA) was demonstrated in functional assays and its reaction with 125I-t-PA was analyzed by autoradiography following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). When the t-PAI was mixed with an equimolar concentration of t-PA at 37 degrees C, the half-life of free one-chain and two-chain 125I-t-PA was 1.8 and 0.8 min, respectively. The rate of complex formation between 125I-t-PA and t-PAI was similar both in patient plasma, pregnancy plasma and platelet lysates made from platelet-rich normal, patient and pregnancy plasma. The molecular weights of the complexes between t-PA and the inhibitors in patient plasma and in the different platelet lysates were identical, while that of the inhibitor complex formed in pregnancy plasma was found slightly higher by SDS-PAGE indicating that the pregnancy plasma t-PAI differs from the fast-acting t-PAI found in plasma from thrombotic patients and in platelet lysates.
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PMID:Plasminogen activator inhibitors in plasma and platelets from patients with recurrent venous thrombosis and pregnant women. 308 15

The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V.O.). On the basis of the results, the patients could be classified in 3 groups: good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32). The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p less than 0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p less than 0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients. It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. 310 59

In a pilot study on 9 patients with acute deep venous thrombosis of the leg the fibrinolytic response and the possible thrombolytic effect of desmopressin (DDAVP), when given supplementary to standard heparin treatment, was examined. Six injections of 0.3-0.4 microgram DDAVP/kg b.w. at 12 hours intervals were given. No serious side effects were observed. The fibrinolytic variables that followed showed that plasma levels of t-PA increased significantly and most pronounced after the first injection. Rephlebography 4-7 days after hospitalization showed partial thrombolysis in 7 out of 9 patients. The phlebographic score according to Marder was reduced from 22.7 +/- 12.1 to 18.4 +/- 10.1 (p = 0.018), corresponding to a thrombus size reduction of 19%. No correlation between the level of the fibrinolytic variables measured and the degree of thrombolysis in the individual patients, could be demonstrated in this small number of patients.
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PMID:A pilot study; desmopressin (DDAVP) in the treatment of deep venous thrombosis. 310 64

Recombinant human tissue-type plasminogen activator (rt-PA) was given to seven patients with phlebographically documented deep vein thrombosis at a dose of 60-120 mg/day (0.71-1.76 mg/kg body weight/24 h) for 2 to 4 days. rt-PA induced evident recanalization in 6 of 7 cases. The lowest here used dose of 0.71 mg/kg/24 h was thrombolytical highly effective, but a dose of 1.4 mg/kg/24 h and over was accompanied by bleeding from venous puncture sites. Coagulation analysis showed no obvious decrease of fibrinogen, while euglobulin clot lysis time and thrombelastography demonstrated the systemic fibrinolytic activity. Thus, therapy with rt-PA may represent an alternative and effective therapeutic procedure in treatment of venous thrombosis. The initial results make a case for expanded investigational use of rt-PA in patients with deep vein thrombosis to clarify conceivable advantages of therapy with this fibrin selective thrombolytic agent.
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PMID:[Thrombolytic therapy of deep venous thrombosis with rt-PA]. 312 42

An enzyme-linked immunosorbent assay for fragment D-dimer was developed with the use of two monoclonal antibodies directed against specific non-overlapping antigenic determinants, present in fragment D-dimer of crosslinked fibrin but not in fragment D of non crosslinked fibrin or of fibrinogen. The lower limit of sensitivity of the assay when applied to human plasma, is 25 ng/ml. Concentration of fragment D-dimer in plasma from healthy individuals was 177 +/- 83 ng/ml (mean +/- SD). In plasma of 11 out of 12 patients with phlebographically confirmed acute deep vein thrombosis, fragment D-dimer levels were significantly increased. Fragment D-dimer was not increased in 9 out of 10 patients with recurrent idiopathic deep vein thrombosis during clinically silent episodes. Total t-PA antigen and free t-PA antigen concentrations were measured using previously developed ELISAs. Nine of the 12 patients with acute deep vein thrombosis showed a significant increase of total t-PA antigen (from 8.6 +/- 6.9 ng/ml to 21 +/- 16 ng/ml) after venous occlusion but in 3 of these free t-PA remained undetectable. Five of the 10 patients with recurrent deep vein thrombosis responded to venous occlusion with a significant increase of total t-PA antigen (from 6.7 +/- 3.2 ng/ml to 14 +/- 7.9 ng/ml) but, in all patients, free t-PA antigen remained undetectable. It is concluded that the combined assays of total and free t-PA antigen and of fragment D-dimer may be useful for the evaluation of the dynamics of the fibrinolytic system in physiological and pathological conditions.
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PMID:Fibrinolytic response and fibrin fragment D-dimer levels in patients with deep vein thrombosis. 312 14

The troublesome sequelae of pulmonary embolism (PE) and deep vein thrombosis (DVT) justify an aggressive therapeutic approach. Results of anticoagulation in patients with DVT have shown that a significant percentage of patients have no clot resolution and may progress to develop the postphlebitic syndrome. Lytic therapy has been more effective, with patients showing improvement within 24 h of treatment. This approach has also been found to compare favorably with anticoagulation in the treatment of PE. Preliminary research also suggests a potential role for recombinant human tissue-type plasminogen activator to resolve PE.
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PMID:Fibrinolytic therapy for deep vein thrombosis and pulmonary embolism. 313 Oct 6

In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and fibrinolytic activity were measured in these samples. During venous stasis, plasminogen activator inhibitor (PAI) activity decreased in almost all patients (81 of 83), from a median value of 8.2 to 2.9 U/mL (P less than .001, Wilcoxon signed-rank test). Because PAI-1 antigen augmented from a median value of 16 to 19.2 ng/mL (P less than .001), the decline in PAI activity was attributed to an increase in t-PA antigen from a median value of 10 to 21.7 ng/mL (P less than .001). Neutralization of PAI activity thus reflects the patient's capacity to overcome basal inhibitory potential through t-PA release. Based on residual PAI activity after 10-minute stasis, patients were classified as good or bad responders (PAI activity below detection limit, ie, less than or equal to 1.0 and greater than 1.0 U/ml, respectively). Good responders had a significantly higher fibrinolytic response after stasis than bad responders (median euglobulin clot lysis time 60 v 180 minutes; dilute whole blood clot lysis time 60 v 120 minutes; fibrinolytic activity on fibrin plates 7.7 v 0 U/mL). Furthermore, good responders, as compared with bad responders, had higher t-PA release (median 16.5 v 11.5 ng/mL), lower basal PAI activity (median 4.8 v 11.2 U/mL), and lower basal PAI-1 (median 11 v 21 ng/mL) and u-PA antigen (median 7.9 v 9.0 ng/mL, P less than .02). Hypofibrinolysis, as defined by the inability of released t-PA to overcome PAI-1 basal inhibitory potential, was observed in 45 of 83 patients (54%) and resulted either from an insufficient release of t-PA or from an increased basal PAI activity.
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PMID:Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis. 313 60

Alteration of the fibrinolytic system is considered to be important in the development of deep venous thrombosis (DVT). Using specific assays for tissue plasminogen activator (t-PA) activity, t-PA inhibitor (PAI) and t-PA antigen, we measured these activities in 16 women who developed DVT during their pregnancies. A group of 24 healthy females of comparable age was studied as controls. PAI was increased in 87% of these patients compared to the healthy controls. In some of these patients a defect in release of t-PA from vascular endothelium was found as well. The site at which blood was sampled for analysis appeared to be an important criterion in the ex vivo assessment of functional t-PA reserve and PAI levels, though relatively less so for the latter measurement. The unaffected lower limbs, relative to the unaffected upper limbs, showed an increase in PAI and a demonstrable decrease in t-PA release, both representing increased risk factors for rethrombosis. The affected lower limbs showed similar but more accentuated changes in these parameters.
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PMID:Altered fibrinolysis in DVT: influence of site of sampling. 314 91


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