Venous thrombolysis

Ouriel K, Gray B, Clair DG, Olin J. Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis. J Vase Interv Radiol. 2000 11 295-298. 

In order to compare the effects of 7E3F(ab )2 on arterial versus venous thrombolysis, a canine model was employed in which thrombosis was electrically induced simultaneously in the carotid artery and jugular vein [159], Whilst 7E3F(ab )2 (0.8mg/kg i.v.) prevented reocclusion in the carotid artery after thrombolysis, no effect was seen on rethrombosis in the jugular vein, reflecting the different thrombotic mechanisms in the arterial and venous circulation. 

Bousser MG. Cerebral venous thrombosis nothing, heparin, or local thrombolysis Stroke 1999 30 481 83. 

Spearman MP, Jungreis CA, Wehner JJ, Gerszten PC, Welch WC. Endovascular thrombolysis in deep venous thrombosis. Am J Neuroradiol 1997 18 502-506. 

Venous thrombectomy may be performed to remove a massive obstructive thrombus in a patient with significant iliofemoral venous thrombosis, particularly if the patient is either not a candidate for or has not responded to thrombolysis. Full-dose anticoagulation therapy is essential during the entire operative and postoperative period. These patients need indefinite oral anticoagulation therapy targeted to an INR of 2.5 (range 2.0 to 3.0). 

Grunwald MR, Hofmann LV. Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis. J Vase Intern Radiol. 2004 15 347-352. 

Burkart DJ, BorsaJJ, Anthony JP Thurlo SR, Thrombolysis of acute peripheral arterial and venous occlusions with tenecteplase and eptifibatide a pilot study. 

Venous thrombosis is produced in rats by insertion of a stainless steel wire coil into the inferior caval vein. Platelets as well as plasmatic coagulation are activated on the wire coil. Thrombus formation onto the wire is quantitated by measuring the protein content of the thrombotic material isolated. The kinetics of thrombus formation show an increase in weight and protein content within the first 30 min followed by a steady state between thrombus formation and endogenous thrombolysis leading to a constant protein content of thrombi between 1 and up to 48 h following implantation of the wire coil. Thrombosis incidence in untreated control animals in this model is 100%. The test is used to evaluate antithrombotic and thrombolytic properties of compounds in an in vivo-model of venous thrombosis in rats. 

De ite differmces in their mechanisms of action and in vitro activities, pentasaccharide, DX-9065a and TAP have been shown to be effective antithrombotic agents in experimental models of venous thrombosis, coronary artery occlusion, arterial thrombolysis and acute reocclusion, restenosis after angioplasty, dialysis, and DIG. Pentasaccharide has also demonstrated measurable antithrombotic effects in human trials. Both TAP and DX-9065a produce measurable in vitro anticoagulant effects. In contrast, pentasaccharide does not produce an anticoagulant effect by the typical clot based assays. Thus, with fector Xa inhibitors there is not necessarily a correlation between current lab assays and antithrombotic efficacy as there is with heparin. 

This is a common medical emergency (despite some possible lessening in frequency with the advent of thrombolysis for myocardial infarction). The approach should be to reassure the intensely anxious patient, who should sit upright with the legs dependent to reduce systemic venous return. A loop diuretic, e.g. frusemide (furosemide) 40-80 mg i.v., is the mainstay of therapy and provides benefit both by a rapid and... 

Fibrinolytic system the mode of action of drugs that promote fibrinolysis (fibrinolytics) and their uses to lyse arterial and venous thrombi (thrombolysis)... 

Embolic detachment of components of venous or mural thrombi can sometimes be involved in the development of thromboembolism or cholesterol embolization. There is a 10% incidence of pulmonary embolism during thrombolysis, lethal in 0-5% (5), pointing to the risk of detachment of white components of venous thrombi, especially if large veins, such as those in the pelvis, are involved (6). However, the risk has not been proven to exceed that reported in patients treated with heparin and/or oral anticoagulants. 

The incidence of hemorrhagic complications is particularly high when high doses of streptokinase are used in the treatment of deep venous thrombosis (31). High-dose streptokinase thrombolysis for 2-3 days with an initial dose of 500 000 units followed by a maintenance dose of 3 600 000 U/day led to a 10% rate of major spontaneous bleeding complications, with a fatal outcome in four older subjects out of the total of 98 patients. The fatahty rate of bleeding caused by streptokinase amounts to 7% in patients with peripheral arterial occlusion, but is much lower in younger patients with venous thromboembolism. 

The present report outlines studies with fibrolase in several different animal thrombosis model systems. Infusion of fibrolase proximal to an occlusive thrombus produces rapid and effective thrombolysis in carotid (22) and renal arterial, and iliac venous thrombosis model systems (23). Recently the recombinant form of fibrolase has been purified from a yeast expression system (24). It appears to be identical in all respects to the natural enzyme and has been used successfully in the carotid arterial thrombosis model system (22). Both natural and recombinant forms of the enzyme have effective thrombolytic activity in the different animal models employed there are no observable side effects nor toxicity, and minimal or no observable hemorrhaging. 

In the iliac venous thrombosis model system six animals were studied with good lysis observed venographically in five (23). Figure 2 presents representative venograms illustrating the effectiveness of thrombolysis induced by selective application of natural fibrolase. No toxicity, little or no hemorrhaging, and no evidence of other side effects were observed in the animals studied. These studies again demonstrate the favorable therapeutic potential of native fibrolase. 

The present results demonstrate that natural fibrolase exhibits effective in vivo thrombolytic activity in several animal thrombosis model systems. Infusion of the enzyme proximal to an occlusive thrombus induced rapid and specific thrombolysis in rabbit renal arterial and iliac venous thrombosis model systems. No evidence of hemorrhaging or alterations to the hemostatic system were observed in these studies. Additionally, no toxicity was observed and no angiographic, histologic, or functional evidence of side effects were obtained. The enzyme rapidly lysed 48 hr aged thrombi in the venous thrombosis model. This suggests that one of the primary mechanisms of thrombus resistance to PA-based agents. 

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