Urokinase Infusion Research Articles

Catheter-Directed Thrombolysis for the Treatment of Acute Iliofemoral Deep Venous Thombosis

Objective: Acute iliofemoral deep venous thrombosis (DVT) is a serious venous thrombotic disorder with potentially morbid post-thrombotic sequelae. The purpose of this report is to present our single-centre evolution of technique and the results of catheter-directed thrombolysis for the treatment of acute iliofemoral DVT, and put it into perspective with current literature. Patients and methods: Between May 1988 and April 2000, 54 patients were treated with catheter-directed thrombolysis for occlusive iliofemoral and vena caval thrombosis. Average age was 45 years (range 17-68 years) and the duration of leg symptoms was 5.2 days (range 2-30 days). Routine vena caval filters were not used, although caval filters were inserted in patients with irregular and non-occlusive vena caval thrombus. Initially, urokinase infusion via a right jugular vein and/or contralateral femoral vein approach was used, delivering a 250000-500000 U bolus followed by continuous infusion of 250000-300000 LVh. Catheter delivery has evolved to an ultrasound-guided popliteal or posterior tibial vein puncture and the use of recombinant tissue plasminogen activator at a bolus dose of 4–8 mg followed by 2–4 mg/h. All patients received heparin infusion at 500-1000 U/h. Results: Fifty-one of the 54 patients had successful catheter positioning. Forty-five (83%) had a successful outcome. Of those that failed, 2 were treated with a known chronic occlusion and in 2 patients plasminogen deficiency was suspected. Two patients had persistent iliac vein lesions which led to early re-thrombosis. Overall, 14 (26%) were asymptomatic, 28 (52%) demonstrated moderate improvement, 6 (11%) showed mild improvement and 6 (11%) had no clinical improvement. Serious complications occurred in 5 patients (9%). Four (7%) required blood transfusion and 1 (2%) required operative evacuation of an inguinal haematoma with repair of the common femoral vein. Eight patients (15%) developed a puncture site haematoma and 1 patient (2%) had a guidewire perforation of the common femoral vein. Conclusions: Catheter-directed thrombolysis is the preferred treatment for symptomatic iliofemoral DVT. Following successful lysis, residual iliac vein lesions should be corrected with balloon angioplasty and stenting if necessary. Considering the current results and those of contemporary series, a successful outcome can be anticipated in 80-85% of patients, with a significant improvement in quality of life when compared with standard anticoagulation.

Percutaneous Fibrin Sheath Stripping versus Transcatheter Urokinase Infusion for Malfunctioning Wellpositioned Tunneled Central Venous Dialysis Catheters: A Prospective, Randomized Trial

To compare central dialysis catheter patency rates after stripping procedures with those after urokinase (UK) infusion. Fifty-seven tunneled catheters with either (i) flow rates less than 250 mL/min and established baseline flow rates > or = 300 mL/min or (ii) flow rates 50 mL/min less than higher established baseline flows were prospectively randomized to undergo stripping procedures (n = 28) or UK infusion (n = 29) at 30,000 U/h via each port concurrently, for a total 250,000 U. Success and patency were determined by dialysis at normal flow rates (> or = 300 mL/min) or at the previously established higher baseline rate. Flow rates were monitored weekly. Primary patency ended with catheter malfunction or removal. Kaplan-Meier survival analysis was used to construct survival curves. In the stripping group, initial clinical success was 89% (25 of 28). The 15-, 30-, and 45-day primary patency rates were 75% (n = 20), 52% (n = 13), and 35% (n = 8), respectively. The median duration of additional function was 32 days (95% CI: 18-48 d). In the UK group, initial clinical success was 97% (28 of 29). The 15-, 30-, and 45-day primary patency rates were 86% (n = 21), 63% (n = 13), and 48% (n = 9), respectively. The median duration of additional patency was 42 days (95% CI: 22-153 d). The Wilcoxon test for equality detected no significant difference in the survival curves for the two treatment groups (P = .236). There is no significant difference in time to primary patency between the two methods. Both allow temporary catheter salvage in most patients.

Partial venous thrombosis of the pancreatic allografts after simultaneous pancreas-kidney transplantation.

Despite new advances in transplantation, complete venous thrombosis (VT) of the pancreas after simultaneous pancreas kidney (SPK) transplantation usually results in graft loss. Data are limited regarding the outcome and treatment of partial VT of the pancreas allograft. From July 1994 to December 1999, 126 patients with IDDM/end-stage renal disease underwent SPK with systemic bladder drainage at the University of Miami. We retrospectively reviewed our experience regarding the outcome and treatment options of partial VT of the pancreas allografts. From July 1994 to April 1997, partial VT was not seen in the first 66 SPK patients induced with anti-CD3 rnAb and oral or intravenous (i.v.) tacrolimus (TAC) in the operating room. From May 1997 to June 1999, 14 (29%) out of 48 patients had VT. These cases were identified following the i.v. use of TAC with anti-IL-2R antibody-induction therapy (7/15) or without (7/33). Partial thrombosis of the splenic vein (PTSV) was documented in 10 patients, 2 had complete thrombosis of the splenic vein (CTSV), 1 had partial thrombosis of the superior mesenteric vein (PTSMV), and 1 patient had PTSV and PTSMV. These were identified incidentally during routine color Doppler ultrasonography (CDU). None of these SPK recipients demonstrates a change in clinical parameters. The first 8 patients were systemically heparinized, followed by oral anticoagulation, except 1 patient with CTSV. He progressed to complete thrombosis of the pancreas allograft and was treated with percutaneous thrombectomy and urokinase infusion, followed by heparinization and oral anticoagulation. One patient required exploration for bleeding. In an attempt to reduce the morbidity of heparinization, we treated the next 6 patients with PTSV with aspirin followed by serial CDU. All 14 patients had preservation of the endocrine and exocrine pancreatic functions. CDU showed resolution with recanalization of the thrombosed vein(s). From July 1999 to December 1999, 12 SPK recipients were administered TAC orally with or without induction therapy with anti-IL-2R antibody. So far, in this group, VT has not been identified. In summary, a total of 14 out of 126 patients (11%) had isolated VT with a mean follow-up of 36.4 months. Based on our experience, we suggest that extensive VT after pancreas transplantation, including splenic and superior mesenteric VT, be treated with heparin and subsequent oral anticoagulation for 3 months. For more limited, partial splenic VT, aspirin may be sufficient. Follow-up CDU is critical for a successful outcome. The i.v. use of TAC appears to be a risk factor for the increased incidence of VT. Currently, using IL-2rmAb as induction, TAC is started orally on postoperative days 3 or 4 and aspirin on postoperative day 2.

Evaluation of Thrombolysis and Angioplasty in a Porcine Iliac Artery Thrombosis Model: Application of Endovascular Stent-Graft–Induced Thrombosis

To develop a novel endovascular thrombosis model in the porcine iliac artery for the evaluation of thrombolysis and angioplasty. A stent-inversion-graft (SIG) model combining either a 3-mm or 5-mm tapered expandable polytetrafluoroethylene (ePTFE) graft attached within a self-expandable, 10-mm nitinol stent was placed in the left common iliac artery via an ipsilateral common femoral artery approach in 24 pigs. When the iliac artery was thrombosed, urokinase (250,000 IU) plus heparin (1,000 units) were pulse sprayed via a contralateral femoral approach (n = 12). Saline pulse-spray was used as a control group (n = 12). Balloon angioplasty was performed to eliminate the stenotic tapered graft within the stent after successful thrombolysis. The efficacy of the thrombolysis was assessed with use of intravascular ultrasound (IVUS) and arteriogram. Both the 3-mm tapered and 5-mm tapered SIG models caused iliac artery occlusion in 22 +/- 5 and 41 +/- 9 minutes, respectively, after the deployment. Luminal patency was re-established successfully in all occluded arteries after urokinase infusion. Angioplasty was successful in eliminating the tapered stenosis and restoring the normal diameter in all iliac arteries treated with urokinase. Complete thrombolysis was achieved in both models treated with urokinase. This novel endovascular approach of inducing arterial thrombosis is simple to perform and reliably produces arterial thrombosis. The intraluminal stenosis is also amenable to angioplasty. This model is useful for the evaluation of antithrombotic treatment modality and adjunctive endovascular interventions.

Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity

Purpose: Thrombolysis protects the structural and functional integrity of vein wall in an experimental model of acute deep venous thrombosis (DVT) immediately after treatment, but late sequelae have not been studied. We designed experiments to compare the effects of thrombolysis and surgical thrombectomy at 4 weeks after the treatment of DVT.Methods: DVT was produced bilaterally in male mongrel dogs by proximal and distal femoral vein ligation. Five dogs underwent sham operation. After 48 hours, the ligatures were removed, and the thrombosis was treated with either Fogarty balloon catheter thrombectomy (shear force, 60 g; n = 6) or catheter-directed urokinase infusion (4000 U/min for 90 minutes; n = 6). At 4 weeks, patency and valvular competence were determined by duplex ultrasound scanning. Thrombogenicity was studied by the measurement of radiolabeled fibrin and platelet deposition. Veins were explanted and prepared for histologic examination, scanning electron microscopy, and functional studies in organ chambers.Results: All veins were patent at 1 month. Recanalized thrombus was observed histologically in four (66%) thrombectomized veins, one (17%) thrombolyzed vein, and none of the sham-operated veins (P = .04). Scanning electron microscopy demonstrated similar luminal endothelial cell loss (11%–25%) in all three groups. Platelet and fibrin depositions were not different among groups. Valvular incompetence (reflux duration, >0.5 sec) did not differ significantly in the groups (thrombectomized veins, 2 of 12 (17%); thrombolyzed veins, 0 of 12 (0%); P = NS). In organ chamber studies, endothelium-dependent relaxations to calcium ionophore, but not adenosine diphosphate, were inhibited by an antagonist of nitric oxide production after thrombectomy (P < .05, thrombectomy vs sham- and thrombolysis-treated veins). All veins relaxed to exogenous nitric oxide.Conclusion: Both thrombectomy and thrombolysis restored patency and achieved similar valvular competence. Surgical thrombectomy, however, resulted in more residual thrombus and contributed to changes in endothelium-mediated relaxations at 4 weeks. Thrombolysis maintained both structural integrity and endothelial function.

Direct Graft Puncture with Use of a Crossed Catheter Technique for Thrombolysis of Peripheral Bypass Grafts

To determine the efficacy and safety of direct graft puncture of peripheral arterial bypass grafts with placement of retrograde and antegrade catheters within the graft for thrombolytic therapy. This study also evaluated potential clinical benefit to patients. A retrospective study was performed on 19 patients with 24 peripheral bypass grafts and lower extremity ischemia of less than 1 month duration. Thrombolysis was performed with a continuous high-dose infusion of urokinase. Successful lysis was defined as greater than 95% clot dissolution with antegrade flow within the graft. Technical success was achieved in 17 of 19 patients (89%). The complexity of operative intervention was diminished in 12 of 19 patients (63%). The major complication rate (16%) was significantly higher and, therefore, this technique has a role for patients in whom traditional access is not optimal, such as in those in whom access cannot be achieved or in those with long bypass grafts. Direct graft puncture with placement of catheters across the proximal and distal anastomoses of bypass grafts is a safe method of access, with a major complication rate similar to conventional access techniques. This mode of graft access demonstrates efficacious thrombolysis and acts as a conduit for ancillary procedures.

Endovascular Treatment of Multiple Visceral Artery Paradoxical Emboli With Mechanical and Pharmacological Thrombolysis

Purpose: To report a case of paradoxical emboli to multiple visceral vessels treated with both mechanical (AngioJet device) and pharmacological (urokinase) thrombolysis.Methods and Results: A 72-year-old man presented with a 48-hour history of symptomatic right renal ischemia, which was treated with heparinization. Five days later, an abrupt creatinine elevation prompted arteriography, which demonstrated thromboembolism of the superior mesenteric artery (SMA) and both renal arteries. The AngioJet aspiration device was employed to successfully remove the clot from the SMA; urokinase infusion restored flow to the left kidney. At the 16-month follow-up evaluation, the patient was normotensive without medication and had a stable creatinine (1.4 mg/dL).Conclusions: Because of its speed and minimal morbidity, the AngioJet device may be an attractive alternative to surgical embolectomy or pharmacological thrombolysis in highly selected cases of acute visceral artery thromboembolism.

Pharmacomechanical Thrombolysis with Use of the Brush Catheter in Canine Thrombosed Femoropopliteal Arterial PTFE Bypass Grafts

To assess the efficacy, acute endothelial changes, and distal arterial emboli after use of the Cragg thrombolytic brush catheter in mature thrombosed polytetrafluoroethylene (PTFE) femoropopliteal arterial grafts in canines. PTFE femoropopliteal arterial grafts were implanted in 10 canines and were allowed to mature for approximately 4 weeks. The grafts were thrombosed by mechanical means and allowed to remain thrombosed for 24-72 hours. Through a left carotid cut-down, standard Seldinger arterial puncture was performed, followed by catheterization of the thrombosed graft. A soft, low-speed, brush (6 mm in diameter) aided by preprocedure pulse-spray urokinase infusion was utilized for thrombolysis. The native vessels, just proximal and distal to the anastomosis, were evaluated microscopically for endothelial damage. Arteriography was used for assessment of distal embolus. All grafts were successfully thrombosed before thrombolysis. One graft could not be traversed with a wire and catheter and was, therefore, not treated. Immediate preprocedure pulse-spray urokinase infusion in the remaining nine grafts did not reconstitute antegrade flow in any instance and left significant amounts of residual thrombus in all treated grafts. Mechanical brush thrombolysis reconstituted antegrade flow in all nine treated grafts and complete graft thrombolysis was obtained in most. This was accomplished in a mean time of less than 4 minutes. Emboli were noted angiographically in 67% of cases. Histologic studies showed vessel wall damage limited to the intima or media in 67% of anastomoses. This method offers a simple and rapid means of recanalizing thrombosed PTFE femoropopliteal arterial grafts in the studied model. This technique provides a means of rapidly "debulking" most intragraft thrombi. This may result in a shorter course of thrombolytic infusion. Potential benefits may include shortening the total treatment time and decreasing morbidity and cost associated with percutaneous thrombolysis. The occurrence of distal emboli in a majority of cases is a concerning limitation of this technique.

Treatment of failed native arteriovenous fistulae for hemodialysis by interventional radiology

We studied the feasibility, technical problems, safety, and effectiveness of percutaneous declotting of thrombosed native arteriovenous fistulae for hemodialysis. Between 1992 and 1998, 93 declotting procedures were performed in 73 consecutive upper limb native fistulae (forearm 56 and upper arm 17), and 162 procedures were performed in 78 prosthetic grafts using manual catheter-directed thrombo-aspiration, with or without previous urokinase infusion. Detection of restenosis by clinical surveillance led to redilation or stent placement. Rethrombosis in four forearm and six upper arm fistulae were treated by 20 further declottings by aspiration. The initial success was 93% in the forearm and 76% in the upper arm (99% in grafts). The complications included one pulmonary embolism, one acute pseudoaneurysm, and one blood depletion requiring transfusion. Primary patency rates at one year were 49% in the forearm and 9% in the upper arm (14% in grafts). Secondary patency rates were 81 and 50% at one year, respectively (83% in grafts). Reinterventions were necessary every 19.6 months in the forearm and every 5.7 months in the upper arm (every 6.4 months in grafts, P < 0.05). Stents were placed in 11% of forearm fistulae and in 41% of upper arm fistulae (45% of grafts) for treatment of acute rupture (5 out of 19), stenosis recoil (6 out of 19), and early (< 6 months) recurring stenosis (8 out of 19). The percutaneous declotting of forearm fistulae by manual catheter-directed thrombo-aspiration was effective in more than 90% of cases and yielded 50% primary and 80% secondary patency rates at one year. The results were poorer in upper arm fistulae. The need for maintenance reinterventions was three times smaller in forearm fistulae than in upper arm fistulae and grafts.

Mechanical versus Chemical Thrombolysis: An In Vitro Differentiation of Thrombolytic Mechanisms

To assess differing mechanisms of thrombolysis determining time to reperfusion, completeness of thrombus dissolution, and embolic potential. An in vitro perfusion model designed to mimic arterial flow conditions was created. Bifurcated limbs allowed continuous flow through one channel and the placement of radiolabeled (iodine-125) thrombus housed in a 5-cm segment of polytetrafluoroethylene graft in the other. The three experimental groups consisted of a standard continuous urokinase infusion, a pulsed pressurized injection of saline, and a similar injection with urokinase. A continuous infusion of 5% dextrose served as a control group. Time to reflow (as assessed with ultrasonic flow monitoring), completeness of thrombus dissolution (I-125 liberated into solution), and the number and size of embolic particles produced (detected by a series of graduated filter sizes) were analyzed. Time to reflow was significantly faster for both groups when pressurized injections were used (P < .001). There was no reflow in the control arm at 90 minutes. Completeness of thrombus dissolution was higher when a continuous infusion of urokinase was used in comparison to either of the power injection groups or the control (P < .05). The amount of embolic debris produced was significantly lower with a continuous infusion of urokinase compared with either of the power lysis groups (P < .05), but significantly greater than the control arm (P < .001). The size of the embolic particles in the power pulsed lysis groups was significantly decreased by the addition of urokinase (P < .05). Reflow is more rapidly established by the use of mechanical means. However, a less complete dissolution of thrombus in conjunction with a greater amount of embolic debris is achieved with this approach. The size of the embolic particles produced is reduced by the addition of a thrombolytic agent.

The Effects of Thrombus, Thrombectomy and Thrombolysis on Endothelial Function

Objective: this study was undertaken to examine and compare the effects of thrombus, thrombectomy, and thrombolysis on endothelial function as measured by endothelium-dependent vasorelaxation (EDR). Methods: adult, male New Zealand white rabbits underwent ligation of the left common iliac to femoral artery to induce thrombosis and were then randomly assigned to one of five groups, n=6 in each. Group A consisted of ligation and thrombosis for 4 h. Group B underwent similar ligation for 4 h, but without intraluminal thrombus present. Following 4 h of ligation and thrombosis, Group C underwent thrombectomy while group D was treated with urokinase (UK), 4000 U/min for 30 min. Group E underwent UK infusion alone. The right external iliac artery served as control vessel in each group. All arteries were removed and endothelial function was determined by measuring EDR. Results: the presence of thrombus reduced EDR by 50% (group A) compared to control. Vessels with interrupted flow, but not exposed to thrombus, retained normal EDR (group B). Thrombectomy decreased EDR significantly (group C) compared to thrombolysis (group D) and control. UK did not significantly alter EDR (groups D, E).Conclusions: exposure of endothelium to thrombus significantly decreases EDR. EDR was not affected by interruption of blood flow in the absence of thrombus. Thrombectomy appeared to cause a further additive insult to the endothelium. In contrast, thrombolysis with UK preserved residual endothelial function. These data suggest that it is important to differentiate the effects of thrombus on endothelium from effects due to thrombectomy or thrombolysis when evaluating treatment modalities for arterial thrombosis.

Outpatient High-Dose Urokinase Infusion Improves Dialysis Catheter Longevity: A Prospective Observational Study

Catheter thrombosis is a major limiting factor affecting catheter survival in hemodialysis (HD). A previous retrospective study highlighted the utility of outpatient intradialytic high-dose urokinase (HDU) infusion in the treatment of HD catheter thrombosis. The present study was designed to prospectively evaluate the effectiveness of 250 000 IU urokinase given as a 3-hour infusion during HD. The infusion would follow detection of a drop in blood flow thought to be secondary to thrombosis [a "thrombotic event" (TE)] after exclusion of nonthrombotic causes of drop in blood flow [a "nonthrombotic event" (NTE)], such as systemic hypotension or suboptimal position of the catheter on x ray. An “event” was defined as a drop in pump blood flow by greater than or equal to 20% of the prescribed blood flow. Twenty patients (mean age 57.7 years; 13 males) with documented or potentially long-term catheters were recruited (total catheters used, 30) from an outpatient HD unit. A variety of catheter types were used. Catheter position was confirmed on x ray. Hemodialysis sessions were monitored for 6 months or until catheter removal (whichever was earlier). Thrombotic and NTEs (mostly related to drop in blood flow) were noted. The use of intradialytic HDU infusions was monitored. Improvement was defined as reestablishment of blood flow to within 10% of prescription. There were 24 TEs in 11 patients and 15 NTEs in 7 patients. Twenty-one of 22 (95%) TEs responded to HDU, with complete restoration of blood flow; in 1/22 HDU-treated instances there was a partial response. For 2/24 TEs the patients underwent catheter stripping with good results. Twelve of 15 NTEs occurred in the first 2 weeks of catheter placement versus 6/24 TEs (p = 0.001, chi-square). Catheter survival was longer than 24 weeks in 12/30 catheters. Nine catheters were lost to NTEs. No catheter was lost secondary to a TE. It is therefore concluded that intradialytic outpatient HDU is useful for the treatment of HD catheter thrombosis. It may obviate/reduce the need for catheter stripping or replacement. Randomized controlled trials with this approach are needed. A higher proportion of NTEs tended to occur earlier after catheter placement compared to TEs.

Outpatient High-Dose Urokinase Infusion Improves Dialysis Catheter Longevity: A Prospective Observational Study.

Catheter thrombosis is a major limiting factor affecting catheter survival in hemodialysis (HD). A previous retrospective study highlighted the utility of outpatient intradialytic high-dose urokinase (HDU) infusion in the treatment of HD catheter thrombosis. The present study was designed to prospectively evaluate the effectiveness of 250 000 IU urokinase given as a 3-hour infusion during HD. The infusion would follow detection of a drop in blood flow thought to be secondary to thrombosis [a "thrombotic event" (TE)] after exclusion of nonthrombotic causes of drop in blood flow [a "nonthrombotic event" (NTE)], such as systemic hypotension or suboptimal position of the catheter on x ray. An "event" was defined as a drop in pump blood flow by greater than or equal to 20% of the prescribed blood flow. Twenty patients (mean age 57.7 years; 13 males) with documented or potentially long-term catheters were recruited (total catheters used, 30) from an outpatient HD unit. A variety of catheter types were used. Catheter position was confirmed on x ray. Hemodialysis sessions were monitored for 6 months or until catheter removal (whichever was earlier). Thrombotic and NTEs (mostly related to drop in blood flow) were noted. The use of intradialytic HDU infusions was monitored. Improvement was defined as reestablishment of blood flow to within 10% of prescription. There were 24 TEs in 11 patients and 15 NTEs in 7 patients. Twenty-one of 22 (95%) TEs responded to HDU, with complete restoration of blood flow; in 1/22 HDU-treated instances there was a partial response. For 2/24 TEs the patients underwent catheter stripping with good results. Twelve of 15 NTEs occurred in the first 2 weeks of catheter placement versus 6/24 TEs (p = 0.001, chi-square). Catheter survival was longer than 24 weeks in 12/30 catheters. Nine catheters were lost to NTEs. No catheter was lost secondary to a TE. It is therefore concluded that intradialytic outpatient HDU is useful for the treatment of HD catheter thrombosis. It may obviate/reduce the need for catheter stripping or replacement. Randomized controlled trials with this approach are needed. A higher proportion of NTEs tended to occur earlier after catheter placement compared to TEs.

Outcome Evaluation of Intra-arterial Infusion of Urokinase for Acute Ischemic Stroke

Pupose: To evaluate the results of intra-arterial urokinase thrombolysis in cases of acute ischemic stroke and to define the factors affecting prognosis. Materials and Methods: Forty-eight patients with angiographically proven occlusion of the intracranial arteries were treated with local intra-arterial infusion of urokinase within six hours of the onset of symptoms. Neurologic status was evaluated on admission and on discharge using the NIH(National Institute of Health) stroke scale score (SSS). When the SSS decreased by at least four points, this was considered indicative of an improved clinical outcome. Results: Complete recanalization was achieved in 17/48 patients (35%), including 8 of 13 (62%) with occlusion of the vertebrobasilar artery (VBA), 9 of 20 (45%) with occlusion of the middle cerebral artery (MCA), and none of 15 with occlusion of the internal carotid artery (ICA). Neurologic status improved in 12 (60%) of patients with MCA occlusion, in five (38%) of those with VBA occlusion and in three (20%) of those with ICA occlusion (P

Deep Venous Thrombosis in the Lower Extremity: Catheter-Directed Thrombolysis

To evaluate the efficacy of catheter-directed thrombolysis in treating symptomatic deep venous thrombosis (DVT) in lower limbs. Materials and Methods: Twenty-six consecutive patients (16 male and 10 female; mean age, 55 years) with lower extremity DVT underwent thrombolytic therapy. The duration of symptoms was 1 -90 (mean, 17) days: 20 days or less in 16 cases (acute DVT) and less than 20 days in ten (chronic DVT). Catheter-directed infusions of urokinase were administered via ipsilateral popliteal veins, and angioplasty or stent placement was per-formed after the thrombolytic procedure. Oral medication of warfarin continued for six months, and for the evaluation of venous patency, follow-up ultrasonography was performed. The total dose of infused urokinase was 1,750,000 -10,000,000 (mean 4, 84,000) IU, and the total procedural time was 25 -115 (mean, 64) hours. Results: Lysis was complete in 16 cases (62%, all acute DVT), partial in five (19%, chronic DVT), and failed in five (19%, chronic DVT). Eight patients with venous stenosis and two with occlusion were treated by means of angioplasty (n=4) or Wallstent placement (n=6). Minor bleeding occurred in six cases and major complications in two (one of pulmonary embolism, and one of multiorgan failure). Conclusion: Catheter-directed thrombolysis with urokinase is effective for the treatment of DVT in lower limbs.

Treatment of Upper-Extremity Phlegmasia Cerulea Dolens with Intra-arterial Thrombolysis

Upper-extremity deep vein thrombosis is a common iatrogenic complication in patients who have had central venous catheters, and is usually associated with mild symptoms. This report is of a 57-year-old craftsman who developed phlegmasia cerulea dolens of his left upper extremity 16 hours after removal of an ipsilateral subclavian vein catheter. The extremity was tensely edematous, hand was mottled, and tips of the digits were cyanotic. Arterial Doppler signals were normal. Fourteen hours of extremity elevation and heparin anticoagulation resulted in no clinical improvement. Duplex ultrasonography and venography showed diffuse thrombosis of the veins of the arm and forearm, but patent axillary and subclavian veins. Due to the severity of the edema and evidence of vascular compromise, an infusion catheter, introduced through the right common femoral artery, was positioned in the left brachial artery and an intra-arterial urokinase infusion of the left upper extremity initiated. Within 12 hours, the patient's left upper extremity improved notably. Ninety-three hours later, the urokinase infusion was stopped and the left upper extremity appeared normal. Follow-up duplex ultrasonography documented no residual thrombus in the deep veins of the left arm and forearm. Six months later, the patient has no residual disability, extremity edema, or limitations in function. An extensive review of the English literature identified no previous reports of intraarterial thrombolysis for upper-extremity phlegmasia cerulea dolens. This case is discussed and pertinent literature reviewed.

Intrapulmonary artery infusion of urokinase for treatment of massive pulmonary embolism: a review of 26 patients with and without contraindications to systemic thrombolytic therapy.

Pulmonary emboli (PE) are a common event seen in over 600,000 patients a year. Occurring suddenly, PE often result in a high rate of mortality. To combat the high rate of mortality, more aggressive therapies including the use of thrombolytics are often indicated. The use of intrapulmonary artery infusion of urokinase has been shown to promote rapid resolution of emboli and restoration of normal pulmonary hemodynamics. The study was undertaken to review the effectiveness and safety of pulmonary artery infusion of urokinase in 26 patients with and without contraindications to the use of systemic thrombolytic therapy. We reviewed the outcomes of 26 patients who received infusion of urokinase, using a usual loading dose of 4,000 U/kg body weight given as a bolus, followed by 4,000 U/kg/h for 12 to 24 h, using either/or unilateral or bilateral infusions. Pulmonary angiograms were obtained prior to and following the urokinase infusions. Intrapulmonary artery infusion of urokinase was given to 26 patients, 9 of whom had contraindications to the use of systemic thrombolytic therapy. Six patients were recent post operative, one was receiving oral anticoagulants, one was receiving chemotherapy with bleeding complications, and one had received cardiopulmonary resuscitation. Twenty of the patients returned to their baseline state (normal heart rate, blood pressure, and p02), one was minimally improved, and five deaths occurred. Of the five deaths, three occurred within 1 h of starting urokinase infusion, the remaining two died more than 36 h after treatment with urokinase as a result of their basic underlying disease. Minor bleeding occurred from puncture sites, two hematomas occurred at the puncture site, and there were two gastrointestinal bleeds, one of which occurred a week post urokinase therapy while the patient was receiving heparin and coumadin. No central nervous system bleeds occurred and no transfusions were required as a result of urokinase intrapulmonary artery infusions. The overall mortality rate in this series was 11.5%. Intrapulmonary artery infusion of urokinase in extensive pulmonary embolism is a safe and efficient treatment in patients with and without contraindication to the use of systemic thrombolytic therapy. With a usual loading dose of 4,000 U/kg body weight, followed by an infusion of 4,000 U/kg/h for 12 to 24 h, it produces significant and rapid resolution of pulmonary emboli with a low morbidity and mortality rate. In our series, the mortality rate was 11.5%, and none of the deaths was the direct result of urokinase therapy.

Mesenteric and portal vein thrombosis in a young patient with protein S deficiency treated with urokinase via the superior mesenteric artery

A 32-year-old man, who was previously healthy, had acute abdominal pain without peritonitis. Diffuse mesenteric and portal vein thrombosis were shown by means of a computed tomography scan. A protein s deficiency was found by means of an extensive workup for hypercoagulable state. Successful treatment was achieved with urokinase infusion via the superior mesenteric artery without an operation. This represents an attractive alternative approach to treating patients with this disease. The previous standard of operative intervention 1 can now be reserved for complications, such as bowel infarction with peritonitis, or for those patients with absolute contraindications to thrombolytic therapy. (J Vasc Surg 1999;30:551-4.)

Percutaneous transluminal angioplasty for intracranial atherosclerotic lesions: evolution of technique and short-term results.

A retrospective analysis of a 9-year experience with balloon angioplasty for intracranial atherosclerotic stenosis was undertaken with the goals of illustrating development of a safe technique for treatment of intracranial atherosclerotic disease and reporting the immediate results in this series of patients. Three distinct periods are defined, based on the technique used. In the early period, in which eight patients were treated, the angioplasty balloon size approximated the vessel size, but was always smaller. Angioplasty was moderately rapid and brief (15-30 seconds). Clinical improvement occurred in seven (87.5%) of eight patients, dissection without consequence occurred in four (50%) of eight, and residual stenosis greater than 50% was found in three (37.5%) of eight. No neurological complications occurred. In the middle period, in which 12 patients were treated, the balloon size approximated the vessel size, but oversizing by up to 0.25 mm was permitted. Angioplasty was extremely rapid and brief. Angiographically visible dissection occurred in nine (75%) of 12 patients, necessitating urokinase infusion in five (41.7%) of 12 and producing abrupt occlusion in one (8.3%) of 12, resulting in death. Occlusion secondary to the recrossing of the lesion occurred in one (8.3%) of 12, resulting in stroke. Good outcome was eventually achieved in 10 (83.3%) of 12. In the current period, in which 50 patients have been treated, the balloon is always undersized and inflation is extremely slow (several minutes). Dissection occurred in seven (14%) of 50 patients, necessitating fibrinolysis in two of 50 (4%, both uneventful) and producing no abrupt occlusion or stroke. Residual stenosis greater than 50% occurred in eight (16%) of 50, with no stenosis greater than 70%. Late restenosis occurred in four (9%) of 44 and successful repeated angioplasty was performed in all four. One guidewire vessel perforation occurred (2%), resulting in the patient's death. Good angiographic and short-term clinical outcome was achieved in the other 49 patients (98%). Extremely slow balloon inflation combined with balloon undersizing results in decreased intimal damage, decreased acute platelet/thrombus deposition, and decreased acute closure. This technique sometimes yields suboptimal angiographic results but achieves the clinical goal safely. Intracranial angioplasty can be safely performed using this technique and modern equipment.

Acute Arterial Occlusions of the Small Vessels of the Hand and Forearm: Treatment with Regional Urokinase Therapy

Arterial occlusions of the small vessels of the forearm and hand may have the same consequences as arterial occlusions in the distal lower extremity. There is limited reported experience with the regional thrombolytic therapy in this setting. The authors reviewed their experience with thrombolytic therapy in acute and subacute arterial occlusions of the distal upper extremity to further clarify its role. Twelve patients with acute or subacute arterial occlusions of the forearm and hand who had ischemic digits and were treated with regional urokinase infusion were identified retrospectively. Their medical and radiology records were reviewed. All 12 patients demonstrated angiographic improvement and 11 patients demonstrated clinical improvement after treatment. Tissue necrosis in four patients led to partial amputation of one digit in two patients and three digits in two patients. Three of these patients had category III ischemia at presentation. The level of resulting amputation was altered in all but one patient. Vasospasm was noted frequently but responded to vasodilators. No significant complications occurred. When therapeutic alternatives are limited to anticoagulation and expectant amputation, regional urokinase infusion can optimize distal runoff, obviate or improve the options for distal surgical bypass, and limit tissue loss.