Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We compared the direct thrombin inhibitor, desulfatohirudin (REVASC) and the indirect thrombin inhibitor, heparin, as adjuncts to thrombolytic therapy with reteplase in a canine model of coronary artery thrombosis. 2. Reteplase (BM 06.022) is a recombinant unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anaesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 210 min with an electromagnetic flow probe. Twenty eight dogs were randomized to receive i.v. heparin (120 iu kg-1 bolus plus 80 iu kg-1 per h) or i.v. hirudin (2.0 mg kg-1 bolus plus 2.0 mg kg-1 per h) 10 min before thrombolysis preceded by i.v. acetylsalicyclic acid (20 mg kg-1) 5 min prior to anticoagulation. Every dog received an i.v. double bolus injection of 0.14 + 0.14 u kg-1 ( = 0.24 + 0.24 mg kg-1) reteplase, 30 min apart, 1 h after thrombus formation. 3. At comparable reperfusion rates (12 out of 12 vs. 15 out of 16 dogs), hirudin enhanced time to reperfusion (14.3 +/- 1.4 vs. 23.2 +/- 3.4 min; P < 0.05) and completely prevented reocclusion after reperfusion in contrast to heparin (0 out of 11 vs. 7 out of 11 dogs; P < 0.05). Coronary blood flow quality was improved by hirudin as shown by a higher maximum blood flow after reperfusion (130 +/- 14.3 vs. 83 +/- 9.3% of baseline; P < 0.05), a higher blood flow level at 20, 30, 40, and 50 min after onset of thrombolysis (P < 0.05) and a longer cumulative patency time (195 +/- 1.7 vs. 166 +/- 12 min; P < 0.05). Activated partial thromboplastin time and buccal mucosa bleeding time were prolonged (P < 0.05) by either anticoagulant, but did not differ significantly between groups. 4. The direct thrombin inhibitor, desulfatohirudin, enhanced thrombolysis, prevented reocclusion and increased blood flow as compared with the indirect thrombin inhibitor, heparin, when investigated at one dose level each and used in conjunction with reteplase.
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PMID:Comparison of desulfatohirudin (REVASC) and heparin as adjuncts to thrombolytic therapy with reteplase in a canine model of coronary thrombosis. 873 26

We sought to determine the efficacy of the combination of argatroban, a direct thrombin inhibitor, and G4120, a platelet glycoprotein (GP) IIb/IIIa blocker, to enhance thrombolysis with alteplase. Platelet-rich thrombus in the rabbit arterial thrombosis model is relatively resistant to alteplase despite the addition of aspirin and heparin. The adjunctive use of either direct thrombin inhibitors or GP IIb/IIIa inhibitors in thrombolysis has been investigated with encouraging, but limited, success. The usefulness of combining both agents as adjunctive therapy to thrombolysis has not been fully explored. Following platelet-rich thrombus formation in the rabbit, argatroban (3 mg/kg), G4120 (0.5 mg/kg), G4120 plus heparin (200 U/kg), or G4120 plus argatroban were intravenously infused over 60 minutes. Alteplase was given as intravenous boluses (0.45 mg/kg) at 15-minute intervals up to 4 doses or until reperfusion. Blood flow and bleeding time were monitored for 2 hours. The combination of G4120 plus argatroban resulted in a persistent patency in 5 of 7 animals compared with 0 of 6 for argatroban alone (p=0.02), 1 of 6 for G4120 alone (p=0.08), and 2 of 6 for G4120 plus heparin (p=0.2). Although during the infusion the bleeding times were longer in the groups that received G4120 (26+/-7.7 minutes vs. 14+/-10 minutes, p<0.05), by the end of the experiment there were no statistically significant differences. Similarly, during the infusion the activated partial thromboplastin times (aPTT) was higher in groups that received heparin or argatroban (99+/-51 seconds vs. 32+/-7.6 seconds, p<0.001), but by the end of the experiment the aPTTs had returned to close to baseline in all groups except the G4120 plus heparin group. These results suggest that lysis of platelet-rich thrombus with alteplase requires the addition of both potent platelet and thrombin inhibitors. Specifically designed agents, G4120 and argatroban, are effective without additional increased risk for bleeding.
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PMID:Combination of a direct thrombin inhibitor and a platelet glycoprotein IIb/IIIa blocking peptide facilitates and maintains reperfusion of platelet-rich thrombus with alteplase. 1100 41

Several studies since 1998 have shown the efficacy of catheter-directed thrombolytic therapy with reteplase. Reteplase is a plasminogen activator that penetrates the thrombus and causes lysis. This catheter-directed approach has been used to treat both arterial and venous occlusions, with a success rate of 72% to 88%. The most serious complication associated with thrombolytic therapy is intracranial hemorrhage. Patients should be admitted to the intensive care unit for monitoring of neurological status, vital signs, laboratory values (hematocrit, hemoglobin level, activated partial thromboplastin time, and fibrinogen concentration), and bleeding or oozing at puncture sites. Staff nurses in the intensive care unit must be aware of this important thrombolytic therapy, its indications, and its implications for nursing interventions.
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PMID:Reteplase: nursing implications for catheter-directed thrombolytic therapy for peripheral vascular occlusions. 1238 13

Pulmonory embolism takes the third place in cardiovascular mortality structure. Separate clinical symptoms don't have adequate sensibility and specificity for pulmonary embolism verification. For pulmonary embolism diagnosis are usually used clinical probability scales. Clinical markers, pulmonic ventricle dysfunction markers, and myocardial injury markers determine risk stratification. Methods for diagnosis and treatment of pulmonary embolism are based on risk levels. In case of suspected pulmonary embolism the treatment should be prescribed immediately without waiting for diagnosis approval. Pulmonary embolism. accompanied with shock and hypotension is. an absolute thrombolytic therapy indication. According to data, provided by authors, efficacy and safety of prourokinase appeared to be as effective and safe as alteplase according to clinical and instrumental criteria. Alteplase effectiveness is higher than prourokinase in case of short anamnesis (<3 days), while in case of long anamnesis (>3 days) proukinase has the advantage of alteplase., To prevent repeated venous thromboembolism should be prescribed indirect anticoagulant (Vitamin K antaonist) or factor Xa inhibitor oral inticoagulant rivaroxaban.
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PMID:Principles for diagnosis and treatment of pulmonary embolism. 3079 35