Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The use of fibrinolytic agents to control the fibrinolytic enzyme system and lyse pathologic fibrin deposits or thrombus has now assumed a position with anticoagulants and vascular surgery in the physician's therapeutic armamentarium. The principal exogenous activators that are used clinically are streptokinase, urokinase, and tissue plasminogen activator. Acute arterial occlusions are more likely than chronic occlusions to respond to thrombolytic therapy, especially if treatment is instituted within a few hours of onset of symptoms and if the disease is due to embolic material rather than in situ thrombosis. Since the duration of drug infusion necessary to lyse arterial thrombus cannot be predicted, patients in whom tissue viability cannot be determined or in whom ischemia cannot be tolerated during the drug infusion interval are not candidates for intraarterial fibrinolytic drug infusion. In treating patients with venous occlusion, thrombolytic therapy is more effective against proximal clots than in calf thrombosis. No protective effect from pulmonary embolism has been noted in trials comparing heparin with streptokinase. Fifty percent of patients with an initial episode of deep venous thrombosis treated within 72 hours of onset will have complete resolution of thrombus with preservation of valve function.
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PMID:Application of thrombolytic therapy in vascular occlusive disease. A surgical view. 311 28

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

An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT-1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI-1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.
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PMID:Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. 325 45

This study consisted of 52 patients admitted for orthopedic surgery and 28 patients admitted for general surgery, who were treated with Sequential Compression Devices (SCD) and Thromboembolic Deterrent Stockings (TEDS) and monitored for the development of deep vein thrombosis (DVT). Coagulation and fibrinolytic profiles were carried out on these patients preoperatively, and on days one, three, and six postoperatively. All patients were followed by I-125-Fibrinogen scanning, Venous Doppler, and Impedance Plethysmography studies for clot detection. In the orthopedic surgery group, six (11.5%) developed DVT, and in the general surgery group, one (3.6%) developed DVT. No patients developed pulmonary embolism. The combined incidence of DVT was 8.8 per cent. A variety of parameters was measured in order to determine whether compression devices prevent a fibrinolytic shut-down commonly seen in the postsurgical patient. A combination of three assays was found to be significant in demonstrating a fibrinolytic response. These parameters were a post-surgical decrease in the plasminogen level, an increase in the level of free protease activity postoperatively, and an increase in the level of tissue plasminogen activator after surgery. 56.3 per cent of all patients treated with SCD and TEDS showed a fibrinolytic response on postoperative day one by a combination of all three of these parameters. In the group of patients that developed DVT none showed an increase in free protease activity, and five of seven showed no significant decrease in plasminogen and no increase in tissue plasminogen activator. Patients who developed thrombosis had measurable differences in their fibrinolytic system compared to those without postoperative thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between postsurgical fibrinolytic parameters and deep vein thrombosis in surgical patients treated with compression devices. 327 80

Pulmonary embolism remains a challenging problem in diagnosis and management for the emergency physician. Although its clinical presentation is protean and often ambiguous, risk stratification can be accomplished based on the predictive power of a limited number of physical and historical characteristics. Ventilation-perfusion lung scanning occupies a central position in the work-up of suspected PE; however, evidence exists that it may be misused by many physicians. A low probability V-Q scan does not exclude the diagnosis of PE. Patients with other than normal- or high-probability patterns of pulmonary ventilation and perfusion on lung scanning require further investigation. Noninvasive venous studies are useful when indicative of proximal deep venous thrombosis, but are normal in many patients with acute PE. Heparin remains the standard of treatment for most patients with PE. Vena cava filters effectively reduce the incidence of recurrent PE in patients with contraindications to anticoagulation. Thrombolytic therapy offers potential advantages in the treatment of patients with shock due to their PE. Case reports of PE treated with tissue-type plasminogen activator, a new thrombus-specific fibrinolytic agent, are encouraging but preliminary.
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PMID:Pulmonary embolism. 328 Mar 1


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