Urokinase Infusion Research Articles

Factors predicting the outcome of intraarterial thrombolysis in peripheral arterial and graft occlusions.

To determine the association between successful intraarterial thrombolysis and the following factors: sex, age, symptoms, duration of symptoms, length of occlusion, conduit type, runoff, and catheter localization. Forty-six patients with acute or subacute occlusions of peripheral native arteries and grafts were treated with continuous intraarterial infusion of streptokinase or urokinase. A univariate chi-square test and logistic regression analysis were used. Successful lysis was achieved in 27 of 46 patients (59%). The logistic regression analysis revealed a significant association between successful thrombolysis and good runoff (p < 0.01). A catheter position above the occlusion resulted in lysis in only one of 11 patients. The variables rest pain and claudication were slightly significant (p = 0.07). None of the other variables were significant, but a trend toward a separate effect of duration of occlusion was found. Good runoff and intrathrombotic infusion are virtual necessities in obtaining a positive immediate outcome in peripheral arterial and graft occlusions. In our study, other factors were less important.

Extraction atherectomy for the recanalization of totally occluded aortocoronary saphenous vein grafts

This report describes the successful treatment of totally occluded aortocoronary saphenous vein grafts with percutaneous transluminal extraction atherectomy (TEC) in three patients with severe angina and high reoperative surgical risk. The method presented here may provide an alternative to overnight urokinase infusion or repeat surgery in high risk patients.

878 Self-expandable metallic stent for superior vena cava syndrome: A safe and effective treatment

Stenosis and occlusion of superior vena cava (SVC) is not a rare entity in oncology. By-pass surgery, radiation therapy, and chemotherapy—when effective—are common treatments. Interventionist radiology offers a new way to solve the venous obstruction. Between April 1993 and January 1995, fourteen pts (11 males), aged 48–72 (median 58 years), presenting with SVC syndrome due either to lung cancer and mesothelioma (11 pts), or to breast, gastric, and kidney carcinomas (3 pts), were treated with a metallic stent caval placement. SVC obstruction was confirmed by means ofcomputed tomography and cavography (this last procedure, including venous pressure measurements, was repeated both after stenting and later at 1,3, and 6 months). Stent placing (GianturcoRosch Z-stent) was carried out via percutaneous femoral vein approach, after a 12–72 hour infusion of Urokinase (only in 6 pts showing significant SVC thrombosis) and caval stenosis dilatation with suitable balloon catheters. Heparin and/or warfarin were given for at least 7 days after the procedure, followed by aspirin (0.3 g daily). hnmediately after the Z-stent implantation, all patients experienced a dramatic symptom resolution. Both caval pressure and lesion diameter improved significantly. No inunediate and late complications or stent misplacements were observed. Two patients had a late recurrence of their SVC syndrome. To date, 10 pts are still alive at 4 to 10 months after stent placement. Stenosis and occlusion of superior vena cava (SVC) is not a rare entity in oncology. By-pass surgery, radiation therapy, and chemotherapy—when effective—are common treatments. Interventionist radiology offers a new way to solve the venous obstruction. Between April 1993 and January 1995, fourteen pts (11 males), aged 48–72 (median 58 years), presenting with SVC syndrome due either to lung cancer and mesothelioma (11 pts), or to breast, gastric, and kidney carcinomas (3 pts), were treated with a metallic stent caval placement. SVC obstruction was confirmed by means ofcomputed tomography and cavography (this last procedure, including venous pressure measurements, was repeated both after stenting and later at 1,3, and 6 months). Stent placing (GianturcoRosch Z-stent) was carried out via percutaneous femoral vein approach, after a 12–72 hour infusion of Urokinase (only in 6 pts showing significant SVC thrombosis) and caval stenosis dilatation with suitable balloon catheters. Heparin and/or warfarin were given for at least 7 days after the procedure, followed by aspirin (0.3 g daily). hnmediately after the Z-stent implantation, all patients experienced a dramatic symptom resolution. Both caval pressure and lesion diameter improved significantly. No inunediate and late complications or stent misplacements were observed. Two patients had a late recurrence of their SVC syndrome. To date, 10 pts are still alive at 4 to 10 months after stent placement.

Thrombolysis and Angioplasty of Chronic Iliac Artery Occlusions

The role of percutaneous angioplasty in the management of chronic iliac artery occlusions is controversial. This article reviews 7 years of experience in treating patients with complete chronic iliac artery occlusions (n = 99) by using thrombolysis and angioplasty. Patients were not excluded due to age or length of the lesion, or severity of underlying peripheral vascular disease. Thrombolysis was conducted with infusion of urokinase at a rate of 60,000-80,000 IU/h for 24 hours. Angioplasty was then performed irrespective of the results of thrombolysis. Seventy-nine percent of patients responded to urokinase, with complete lysis achieved in 55%. Angioplasty was successful in all patients with complete thrombolysis and in 88% of those with partial thrombolysis. The overall success rate was 86%, and more than 80% of surviving patients were symptom free at 5 years. There were seven complications, and the 30-day mortality rate was 2%. Our present results confirm the efficacy of thrombolysis/angioplasty for chronic arterial occlusions.

Safety and efficacy of extended urokinase infusion plus stent deployment for treatment of obstructed, older saphenous vein grafts

This study was designed to determine the safety and efficacy of extended, continuous infusion of urokinase plus stent deployment to treat older saphenous vein bypass grafts obstructed by both thrombus and atheromatous material. Thirty patients with angiographic evidence of thrombus and atheromatous material obstructing older vein grafts (mean age 8.3 years) underwent the combined interventions of urokinase infusion and stent deployment. The continuous infusion of urokinase was administered directly into each obstructed vein graft over a mean of 20.5 ± 8.1 hours (median dose 2.2 ± 0.7 million units). Stents were deployed at the sites of atheromatous obstruction either before (5 patients) or after (25 patients) infusion of urokinase. Twenty-eight of the 30 patients were successfully treated with the combined interventions (success rate 93.3%). In these 28 patients, percent diameter stenosis at the site of obstruction decreased from 86.0% to −0.2% and Thrombolysis in Myocardial Infarction trial flow increased from 1.0 to 2.5. Two patients (6.7%) developed stent thrombosis followed by myocardial infarction (1 with Q-wave infarction, 3.3%) and congestive heart failure. Minor complications included non-Q-wave myocardial infarction (5 patients, 16.7%) and access-site hemorrhage (5 patients, 16.7%). At 2-week follow-up, anginal symptoms were decreased in all 28 successfully treated patients. At 7.2 ± 3.7-month follow-up, 5 of the 28 successfully treated patients (17.9%) had reacceleration of angina and angiographically documented restenosis at the site of stent deployment. Thus, the combined interventions are highly efficacious in treating older vein grafts obstructed by both thrombus and atheromatous material, but are also associated with significant procedural complications including stent thrombosis, myocardial infarction, and access-site hemorrhage.

Initial experience with an intracoronary flow support device providing localized drug infusion: The scimed dispatch catheter

Two cases are presented illustrating the use of a new intracoronary infusion catheter providing flow support using a unique spiral coil design. Good clinical outcomes were obtained employing 4-hr inflations with localized infusion of urokinase at the site of dissection and extensive clot formation, respectively. This low-profile catheter-mounted device may provide an alternative to stent placement in cases of acute dissection complicated by thrombus formation.

Deep venous thrombosis and pulmonary embolism after lung transplantation

The incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung ( n = 87) or heart-lung ( n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted. (J T HORAC C ARDIOVASC S URG 1995;110:540-4)

Treatment of dural sinus thrombosis using selective catheterization and urokinase

Thrombosis of the cerebral dural venous sinuses, cortical draining veins, and deep cerebral veins is a rare clinical finding. Because of its low incidence and multiple etiologies, the optimum therapy for this condition will only be elucidated by a multicenter, randomized prospective study. At our institution, we favor early and aggressive management of cerebral venous sinus thrombosis with transfemoral, venous intradural infusions of the fibrinolytic agent urokinase. To date, treatment of only 13 patients using this technique has been reported in the English literature. This report adds 12 more such treated patients. Despite the presence of preinfusion infarcts in 5 patients, four of which were hemorrhagic, we incurred no major therapeutic morbidity. Functional sinus patency was achieved in 11 of 12 patients, with our only true failure occurring in an individual with symptoms of at least 2 months' duration. Good to excellent clinical outcome was achieved in 10 of 11 patients (one newborn had inadequate follow-up).

Thrombolysis to Treat Arterial Thrombotic Complications of Heparin-Induced Thrombocytopenia

An 80-year-old man with diabetes developed acute ischemia of the right leg secondary to heparin-induced thrombocytopenia while being treated for a pulmonary embolism. For fear of recurrent thrombosis at the operative site, he was treated with cessation of heparin, placement of a Greenfield filter, and intra-arterial infusion of urokinase into the popliteal artery for 36 hours. All arterial thrombus resolved with no complications. One week later he underwent a below-knee popliteal to anterior tibial artery translocated cephalic vein bypass and transmetatarsal amputation for progressive gangrene of the right toes. The graft remains patent 2 years later. This patient represents the eighth case reported in the world literature in which thrombolytic therapy was used to treat arterial thrombotic complications of heparin-induced thrombocytopenia. Five patients were successfully treated without complications, two others required major amputations, and one died of adrenal hemorrhage. Although thrombolytic therapy should be used cautiously for treatment of arterial thrombotic complications of heparin-induced thrombocytopenia, this adjunct may prove useful and safe in selected cases.

A critical appraisal of the small-diameter portacaval H-graft

Background: The ideal portasystemic shunt should prevent variceal hemorrhage and preserve portal flow to reduce hepatic encephalopathy. The partial shunting proposed by Sarfeh effectively controls variceal bleeding while preserving prograde hepatic portal flow. Patients and methods: We analyzed results of the partial portacaval shunt prospectively in 43 patients undergoing small-diameter (8-mm or 10-mm) portacaval H-graft. Patients entered into the study had Child-Pugh class A and class B cirrhosis, and all had documented previous variceal hemorrhages. We used the Sarfeh technique without performing portal collateral ligation. Results: Operative mortality was 5%. Acute graft thrombosis occurred in 3 patients, 2 of whom were successfully lysed by urokinase infusion angiographically, while later graft occlusion occurred in 1 case. Only 1 patient rebled from varices in our late follow-up (14 to 65 months). Prograde portal flow was maintained in 90% of patients undergoing repeat angiography 27 ± 13 months postoperatively. The incidence of all encephalopathy episodes was 16%, with only 1 patient having this complication chronically. Conclusions: The small-diameter portacaval H-graft of Sarfeh is an effective operation for controlling variceal hemorrhage. It preserves hepatic portal perfusion over time in the majority of patients, reducing the risk of encephalopathy. The procedure may be particularly suited for alcoholic cirrhotic patients with less advanced liver disease.

Markers of haemostatic system activation in 80 patients with deep venous thrombosis submitted to fibrinolytic therapy

Summary Plasma levels of thrombin-antithrombin III complexes (TAT) and prothrombin activation fragment F1+2(F1+2) were analysed in 80 patients with phlebographic proven acute deep vein thrombosis (DVT). TAT and F1+2 levels were measured at the time of diagnosis, at 6 and 24 h after the beginning of urokinase infusion, and at the end of fibrinolytic therapy. Patients were allocated into two subgroups according to their thrombus size: one group of 45 patients with a Marder score >25, and a second group of 35 patients with a score 75% (n=44) were compared with those cases where reperfusion was not achieved (lysis 25 and who had no other risk factors for thrombosis showed significant differences in the levels of TAT (p

Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors

We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase

During the last three years, seven patients with severe intraventricular hemorrhage admitted to our clinic were treated with direct intraventricular infusion of urokinase. In each case, hemorrhage extended into the entire ventricular cavity and cast formation as well as an expansion of third and fourth ventricles were found. On the average, both the third and fourth ventricles became clear on the third day and the lateral ventricle on the ninth day after hemorrhage. Five of the seven patients showed good recovery or only moderate disability, and two died. Infection, convulsion, rebleeding, and peripheral or secondary hemorrhage due to the side effects of urokinase was not encountered during therapy. We conclude that this procedure can be applied effectively and safely in severe intraventricular hemorrhage.

Late results of a prospective study of direct intra-arterial urokinase infusion for peripheral arterial and bypass graft occlusions

The outcome of 72 direct intra-arterial urokinase infusions was studied prospectively. Thirty four were performed for native arterial occlusion and 38 for bypass graft occlusion; the immediate success rates were 67.5 and 84% respectively. The overall incidence of complications was 26%. Median follow-up was 36 (range 1–60) months. Seventeen patients (27%) died during follow-up; nine (14%) required a major amputation. Among patients with native arterial occlusion, 29% had no adjunctive procedure after thrombolysis; of these patients, 85% remained patent at a median of 21 (range 3–42) months. Among bypass occluded patients, only two (6%) had no lesion revealed after successful lysis; both bypasses remain patent at 54 and 58 months respectively. For patients treated with balloon angioplasty immediately after successful thrombolysis, 62% with native arterial occlusion remained patent at a median of 39 (range 2–60) months, whereas only 27% of bypass occlusion patients were patent at a median of 11 (range 2–40) months. Of patients requiring a surgical procedure after thrombolysis, 23 new bypasses (15 vein, eight prosthetic) were placed (nine in native arterial occlusion patients, 14 in bypass occlusion patients). In addition, there were 15 other surgical procedures, including six thrombectomies, four vein patch angioplasties, four vein jump grafts and one endarterectomy. The primary and secondary patencies for the 15 new vein bypasses placed were 81 and 88% respectively at a median follow-up of 36 months. Good immediate results were experienced with urokinase thrombolysis for peripheral arterial and graft occlusions. However, multiple adjunctive procedures were required to maintain patency. Balloon angioplasty yielded reasonable late patency for the native arterial group but poor patency for the bypass group. Replacement with a new bypass gave the best long-term patency in both groups. These data suggest that thrombolysis is a reasonable first-line treatment for limb ischemia due to native arterial occlusion. However, for bypass graft occlusion, the results, despite initial success, are not durable.

Percutaneous translumbar inferior vena cava cannulation for hemodialysis

The purpose of this study was to evaluate the percutaneous translumbar approach for long-term hemodialysis catheter access. Seventeen double-lumen hemodialysis catheters were placed percutaneously from the right flank to the inferior vena cava in 12 patients. Catheter placement was successful in all patients. Adequate flow rates were obtained. Seven episodes of thrombosis-related access failure occurred (0.33 episodes/100 days at risk). Two catheters were removed and five catheters were managed with urokinase infusion. Six episodes of infection occurred (0.28 episodes/100 days at risk). Four required catheter removal. Two catheters were removed after defects developed in the catheter. Five catheters were removed electively because catheter hemodialysis was discontinued. Four catheters remained in place. Cumulative patency was 52% at 6 months and 17% at 12 months. Translumbar inferior vena cava hemodialysis catheters represent a valuable alternative in cases in which traditional catheter sites have failed.

Comparison of the Bleeding Potential of Vampire Bat Salivary Plasminogen Activator Versus Tissue Plasminogen Activator in an Experimental Rabbit Model

Vampire bat salivary plasminogen activator (Bat-PA) has significantly greater fibrin specificity than any of the fibrinolytic agents currently in clinical use. This study tests the hypothesis that avoiding fibrinogen depletion may protect against the hemorrhage induced by plasminogen activator treatment. Bat-PA was compared with tissue-type plasminogen activator (TPA) in a randomized, prospective, and blinded study using a rabbit ear puncture model of fibrinolytic bleeding. The two agents were used at equimolar dosages (42 nmol/kg) that yielded similar thrombolytic efficacies in a rabbit femoral artery thrombosis model. Both Bat-PA and TPA prolong primary bleeding to double the baseline values, from between 2.1 and 2.3 minutes to between 4.8 and 5.2 minutes. Rebleeding from hemostatically stable sites during the 3-hour observation period occurred equally often with Bat-PA and TPA, 31% from preinjection sites and 23% to 25% from postinjection sites. The lag time between the time of plasminogen activator injection and the onset of rebleeding was likewise the same for both agents, most occurring at 41 to 57 minutes. However, a greater number of prolonged primary or rebleeding occurrences continued for longer than 10 minutes (63% versus 36%) or longer than 30 minutes (30% versus 10%) after Bat-PA than TPA injection. Animals treated with TPA showed a dramatic decrease in plasma fibrinogen and factor VIII concentrations, but those in the Bat-PA treatment group showed only a slight decrease from control values. The results indicate that fibrinolytic bleeding after plasminogen activator infusion into rabbits did not correlate with the intensity of the plasma proteolytic state. If anything, Bat-PA usage was associated with a higher proportion of more protracted fibrinolytic bleeding episodes, despite the relatively mild lytic state in comparison with that induced by TPA.

Crossover approach with a J-shaped sheath for angioplasty of iliofemoral artery stenoses and occlusions.

Thirty patients with atherosclerotic stenoses or occlusions of iliofemoral arteries were treated from the contralateral approach using a newly designed J-shaped sheath. Seven patients with stenoses and one with an occlusion were successfully dilated with balloon angioplasty. Twenty-two patients with occlusions were treated with urokinase infusion, 16 of whom received coaxial infusion with the J-shaped sheath and catheter. Complete thrombolysis was achieved in 18 patients. The treatment success rate was 100% in the stenotic group and 83% in the occlusion group. Initially, J-shaped sheaths were useful for treatment of iliofemoral artery lesions from the contralateral femoral artery.

Treatment of Acute Mesenteric Venous Thrombosis with Transjugular Intramesenteric Urokinase Infusion

Treatment of Acute Mesenteric Venous Thrombosis with Transjugular Intramesenteric Urokinase Infusion

Intraoperative Urokinase Infusion for Embolic Stroke during Carotid Endarterectomy

Intraoperative Urokinase Infusion for Embolic Stroke during Carotid Endarterectomy

Prolonged urokinase infusion for chronic total native coronary occlusions: Clinical, angiographic, and treatment observations

Prolonged intravascular infusion of urokinase has proven beneficial in reestablishing patency of chronically occluded peripheral arteries and saphenous vein grafts. This study was performed to assess the efficacy and safety of prolonged urokinase infusion as a prelude to angioplasty in chronically occluded native coronary arteries, that had failed standard angioplasty techniques. Twenty-five patients with objective evidence for ischemia in the distribution of a chronic coronary occlusion were referred for percutaneous intervention. Patients were assessed for any potential exclusions from lytic therapy. Urokinase infusion through both a SOS wire and a stable guiding catheter was continued at 100,000-240,000 units/hr for 8-25 hr; patients then underwent attempted balloon angioplasty. Mean duration of urokinase infusion was 20.6 +/- 7.7 hr (total dose 163,000 +/- 52,447 units/hr). Fibrinogen levels dropped slightly with this (300 +/- 129 to 203 +/- 81 mg/dl, P = 0.02). Angiography posturokinase showed improvement in 7 (28%) with regard to coronary flow (> or = 1 TIMI-grade). Angioplasty was successful in 13 (52%), with final angiographic result revealing thrombus in 5 (20%), or dissection 8 (32%). The infusions were well-tolerated with a low incidence of chest pain, 2 (8%) or ischemic ECG response, 2 (8%); myocardial infarction, 2 (8%); or significant bleeding 2 (8%). All patients survived the procedure, with a length-of-hospital stay = 5.1 +/- 4 days. Use of prolonged preangioplasty intracoronary urokinase infusion can be done safely with success in roughly one-half of patients with chronic total native coronary occlusions who have failed prior attempts at percutaneous intervention.(ABSTRACT TRUNCATED AT 250 WORDS)