Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021. RESULTS: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30). CONCLUSION: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

European cost-effectiveness study of uPA/PAI-1 biomarkers to guide adjuvant chemotherapy decisions in breast cancer.

BACKGROUND: This study investigated the cost effectiveness of guideline-recommended (American Society of Clinical Oncology, European Society of Medical Oncology) urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) biomarkers to guide adjuvant chemotherapy decisions for hormone receptor-positive, node-negative early breast cancer patients at intermediate risk of relapse, in France, Germany, and The Netherlands. METHODS: uPA/PAI-1 testing was compared to chemotherapy for all patients and to no chemotherapy in two age-related subgroups (35-49 and 50-75 years). A partitioned survival analysis was performed using patient-level data for survival outcomes and secondary sources. Mean quality-adjusted life years (QALYs) and costs were estimated over a lifetime horizon to calculate the incremental net monetary benefit (INMB) at a willingness-to-pay of €50,000/QALY. Uncertainty was explored through bootstrap and probabilistic sensitivity analysis using 5000 replicates. RESULTS: In the 35-49 year age group, INMBs were negative when uPA/PAI-1 testing was compared to chemotherapy for all patients but positive when it was compared to no chemotherapy for the three countries. In the 50-75 year age group, INMBs of uPA/PAI-1 testing compared to both reference strategies were positive in the three countries, with cost-effectiveness probabilities for the uPA/PAI-1 strategy of 65%, 70%, and 59% for France, Germany, and the Netherlands, respectively, compared with chemotherapy for all patients, and 64%, 58%, and 65%, respectively, compared with no chemotherapy. CONCLUSIONS: uPA/PAI-1 testing could allow the selection of patients older than 50 years requiring chemotherapy in this population, but the cost effectiveness of this strategy is uncertain. Chemotherapy for all patients is the most cost-effective strategy for patients younger than 50 years.

[Cost-benefit study of different thrombolytic strategies in treating 156 patients with symptomatic pulmonary thromboembolism].

OBJECTIVE: To compare the costs and benefits of different thrombolytic strategies with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) in treating acute pulmonary thromboembolism (PTE), with aim of providing optimal thrombolytic medication. METHODS: Data from 156 patients with PTE from January 2006 to December 2011 in Tangshan Gongren Hospital was analyzed retrospectively. All patients were treated by thrombolysis, among them 104 patients were treated with 1×10(4) U/kg of UK and 52 patients were treated with 50 mg of rt-PA. The therapeutic effects of two methods were compared and the complication incidence rate and medical cost were also compared. RESULTS: There were no significant differences in the symptom remission rate, the recanalization rate, and the incidence of complications between UK group and rt-PA group (68.2% vs. 71.2%, 63.5% vs. 73.1%, 14.4% vs. 17.3%, all P > 0.05), but the treatment cost (yuan) of UK group was remarkably lower than that of rt-PA group (408 ± 120 vs. 6500 ± 634, P < 0.01). CONCLUSION: Different thrombolytic strategies with UK and rt-PA yield similar efficacy, however, the medical cost was significant decreased in UK group.

Cost-effectiveness of urokinase and alteplase for treatment of acute peripheral artery disease: comparison in a decision analysis model.

PURPOSE: The cost-effectiveness of urokinase and alteplase for the treatment of acute peripheral artery disease (PAD) was compared using decision analysis. METHODS: A literature-based decision model to evaluate cost-effectiveness was constructed using a base case of a 65-year-old man with acute PAD. Successful treatment outcomes were defined as clot lysis with a subsequent 30-day survival posttreatment. Direct medical costs were assessed from the payer perspective in the United States and analyzed using sensitivity analyses. A Monte Carlo analysis with 5000 patients was performed to obtain mean and incremental cost-effectiveness ratios (ICERs). RESULTS: The mean cost-effectiveness ratio was $67,581 (95% confidence interval [CI], $36,899 to $108,836) per 30-day treatment success for alteplase and $78,729 (95% CI, $43,411 to $130,063 for urokinase). The ICER for urokinase relative to alteplase was $332,309 per additional 30-day treatment success (95% CI, $-565,540 to $1,661,247). Approximately 75% of simulated cases indicated that urokinase was associated with increased costs and increased treatment success compared with alteplase. Results of a post hoc sensitivity analysis indicated that dominance decreased to approximately 10% of cases only under the most strict criteria. CONCLUSION: Decision analysis found an ICER of $332,309 per additional 30-day treatment success for urokinase relative to alteplase in the treatment of PAD from the perspective of the payer in the United States. In about 75% of cases resulting from a Monte Carlo simulation, urokinase was associated with increased costs and slightly increased treatment success compared with alteplase, although this finding was sensitive to the distributional assumptions made concerning certain costs in the model.

Chronic and acute consequences of a post-dialysis urokinase lock on permanent hemodialysis catheter function.

BACKGROUND: To treat permanent hemodialysis (HD) catheter dysfunctions due to thrombosis, as an alternative to pre- and intradialytic instillations/infusions of fibrinolytic agents, for practical reasons, a post-dialysis urokinase lock is often preferred. This study aimed to analyze the consequences on catheter function and the cost/effectiveness of an intermittent post-dialysis urokinase lock. METHODS: A prospective open experimental study enrolling 10 dialysis patients with a Tesio twin catheter locked with either heparin 5,000 IU/mL or escalating urokinase doses. Catheter function was monitored measuring the blood flow obtained with an aspiration pressure of -180 mmHg for 28 consecutive HD sessions. RESULTS: No differences were noticed between the blood flow obtained before and after the lock of the catheter with 5000 U/lumen of urokinase (phase 1), but also with 10,000 U/lumen (phase 2) of urokinase. The incidence of catheter dysfunction episodes in the wash-out in the 1st and in the 2nd urokinase phases were, respectively: 13, 6 and 3% (p<0.05 for both 13 vs. 6% and 13 vs. 3%). 47,000 U of urokinase were necessary to avoid one dysfunction episode potentially treatable with an intradialytic urokinase lock of 10,000 U. Between the average blood flow measured in the initial wash out (230 +/- 27 ml/min) and in the 1st (236 +/- 32 ml/min) and also in the 2nd (247 +/- 34 ml/min) urokinase phases significant differences were noticed (p<0.01 and p<0.05, respectively). CONCLUSIONS: The post-dialysis lock with urokinase is associated with an increase in the catheter blood flow and a re-duction in the occurrence of dysfunction episodes. However, the modest impact on dialysis quality and the apparent unfavorable cost/effectiveness of the prophylactic treatment, call for an investigation of its potential advantages in a larger study.

Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.

BACKGROUND: Despite increasing incidence and morbidity, little evidence exists to inform the best management approach in childhood empyema. AIM: To compare chest drain with intrapleural urokinase and primary video-assisted thoracoscopic surgery (VATS) for the treatment of childhood empyema. METHODS: Children were prospectively randomized to receive either percutaneous chest drain with intrapleural urokinase or primary VATS. The primary outcome was the number of hospital days after intervention. Secondary end points were number of chest drain days, total hospital stay, failure rate, radiologic outcome at 6 mo, and total treatment costs. RESULTS: Sixty children were recruited. The two groups were well matched for demographics; baseline characteristics; and hematologic, biochemical, and bacteriologic parameters. No significant difference was found in length of hospital stay after intervention between the two groups: VATS (median [range], 6 [3-16] d) versus urokinase (6 [4-25] d) (p = 0.311; 95% confidence interval, -2 to 1). No difference was demonstrated in total hospital stay: VATS versus urokinase (8 [4-17] d and 7 [4-25] d) (p = 0.645); failure rate: 5 (16.6%); and radiologic outcome at 6 mo after intervention in both groups. The mean (median) treatment costs of patients in the urokinase arm US dollars 9,127 (US dollars 6,914) were significantly lower than those for the VATS arm US dollars 11,379 (US dollars 10,146) (p < 0.001). CONCLUSIONS: There is no difference in clinical outcome between intrapleural urokinase and VATS for the treatment of childhood empyema. Urokinase is a more economic treatment option compared with VATS and should be the primary treatment of choice. This study provides an evidence base to guide the management of childhood empyema.

Potency and stability of frozen urokinase solutions in syringes.

PURPOSE: The stability and potency of frozen urokinase solutions in syringes were studied. METHODS: To determine the stability and potency of compounded urokinase dilutions after multiple freeze-thaw cycles, a total of 160 syringes containing five urokinase concentrations (2,500, 5,000, 7,500, 12,500, and 25,000 IU/mL) were prepared. For each of the five concentrations tested, two syringes per concentration were reserved for baseline testing. The remaining 150 syringes were frozen at -30 degrees C. After 7 days, half of the syringes (group 1) were thawed at room temperature, tested, and left at room temperature for 12 hours before refreezing. The other half of the syringes (group 2) were kept frozen for 30 days. Thirty days after initial compounding, all syringes were thawed, and the samples' urokinase potency, pH, and physical appearance were evaluated. Syringes were visually inspected for color, clarity, and precipitation. Descriptive statistics were computed for each concentration group and testing day. RESULTS: The compounded dilutions were stable under each experimental condition, with no physical deterioration or loss of in vitro potency after two freeze-thaw cycles. The reduced waste associated with the ability to refreeze unused urokinase could substantially lower the cost of procedures such as thrombolysis after intraventricular hemorrhage and catheter clearance by as much as 95%. CONCLUSION: Dilutions of urokinase 2,500-25,000 IU/mL were stable in single-use syringes after being frozen for 7 days, thawed, and refrozen for another 23 days.

Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis.

PURPOSE: To compare the efficacy, safety, and costs associated with catheter-directed thrombolysis with urokinase (UK) and the recombinant agents alteplase (tissue plasminogen activator [TPA]) and reteplase (recombinant plasminogen activator [RPA]) in the treatment of symptomatic deep vein thrombosis (DVT). MATERIALS AND METHODS: The authors conducted a retrospective analysis on 74 patients (82 limbs) who underwent treatment for DVT. Thrombosed extremities were treated with either urokinase with therapeutic heparin dosing (UK group; 38 limbs), alteplase with subtherapeutic heparin dosing (TPA group; 32 limbs), or reteplase with subtherapeutic heparin dosing (RPA group; 12 limbs). Infusion times, dosages, drug costs, success rates, and complications were compared among the groups. RESULTS: Gender, age, disease location, duration of symptoms, and use of additional interventional therapies did not differ statistically among the three cohorts. Median hourly infused doses, total doses, infusion times, drug costs, and success rates per limb were: UK, 11.3 (10(4)) U/hour, 4.361 million U, 40.6 hours, US dollars 6577, 97.4%; TPA, 0.57 mg/hour, 21.6 mg, 30.8 hours, US dollars 488, 96.9%; RPA, 0.74 U/hour, 21.4 U, 24.3 hours, US dollars 1787, 100.0%. Major and overall complication rates were: UK, 5.3% and 10.5%; TPA, 3.1% and 12.5%; RPA, 8.3% and 16.7%. Infusion times, success rates, and complications were not statistically different among the three groups. Alteplase and reteplase were significantly less expensive than urokinase (P <.001 and P <.01, respectively). CONCLUSION: Catheter-directed thrombolysis for the treatment of DVT is safe and effective, regardless of the agent used. However, the new recombinant agents are significantly less expensive than urokinase.

Tissue plasminogen activator as an adjuvant therapy for pleural empyema in pediatric patients.

The authors retrospectively review the clinical course and outcome of 6 pediatric patients, ranging in age from 2 to 13 years, who were treated with TPA for complex empyema. Efficacy was assessed by evaluating pleural fluid drainage for 6 hours prior to and subsequent to each dose of TPA, as well as by resolution of fever and length of hospital stay. The average volume drained for 6 hours before infusion of TPA was 22.5 mL +/- 18.4 mL, and the average volume 6 hours after TPA therapy was 141.7 mL +/- 28.3 mL, P <.0001. After initiation of TPA therapy, 5 out of 6 patients became afebrile within 48 hours. The median length of stay after initiation of TPA therapy was 6 days, with a range from 4 days to 12 days. A discussion of other current therapies for empyema, along with a comparison of these therapies to TPA regarding the costs of therapies and risk-benefit ratios, is also included.

The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions.

PURPOSE: The purpose of this study was to compare the efficacy, complications, and costs associated with low-dose (<2 mg/h) alteplase (tissue plasminogen activator [t-PA]) versus urokinase for the catheter-directed treatment of acute peripheral arterial occlusive disease (PAO) and deep vein thrombosis (DVT). MATERIALS AND METHODS: A retrospective review was performed during sequential time periods on two groups with involved extremities treated with either t-PA with subtherapeutic heparin (TPA group) or urokinase with full heparin (UK group) at a single center. Treatment group characteristics, success rates, complications, dosages, infusion time, and costs were compared. RESULTS: Eighty-nine patients with 93 involved limbs underwent treatment (54 with DVT, 39 with PAO). The treatment groups were statistically identical (TPA: 45 limbs; 24 with DVT, 53.3%; 21 with PAO, 46.7%; UK: 48 limbs; 30 with DVT, 62.5%; 18 with PAO, 37.5%). The overall average hourly infused dose, total dose, infusion time, success rates, and cost of thrombolytic agent were as follows (+/- standard deviation): TPA, 0.86 +/- 0.50 mg/h, 21.2 +/- 15.1 mg, 24.6 +/- 11.2 hours, 89.4%, $466 +/- $331; and UK, 13.5 +/- 5.6 (10(4)) U/h, 4.485 +/- 2.394 million U, 33.3 +/- 13.3 hours, 85.7%, $6871 +/- $3667, respectively. Major and minor complication rates were: TPA, 2.2% and 8.9%; and UK, 2.1% and 10.4%, respectively. No statistical differences in success rates or complications were observed; however, t-PA was significantly (P <.05) less expensive and faster than urokinase. CONCLUSION: Low-dose t-PA combined with subtherapeutic heparin is equally efficacious and safe compared with urokinase. Infusions with t-PA were significantly shorter and less expensive than those with urokinase.

Use of urokinase in childhood pleural empyema.

Urokinase is an enzyme with a fibrinolytic effect that facilitates pleural empyema drainage through a chest tube. The aim of this study was to assess the risk of pneumothorax, the need for pleural debridement surgery, the persistence of fever, and the number of days in hospital in a group of children with parapneumonic pleural empyema treated with urokinase. This was an uncontrolled retrospective study on children suffering from parapneumonic empyema. Data collected on 17 children treated with urokinase were compared with 11 children treated prior to the advent of urokinase (the "historic" group). The urokinase was instilled in the pleural cavity over a period ranging from 2-8 days, amounting to a median total dose per kilogram of body weight of 18,556 IU (range, 7,105-40,299). Surgical treatment of the empyema involved drainage tube placement and/or debridement of the pleural cavity. Three children developed pneumothorax during their hospital stay, and one more case occurred 6 months after the child had recovered from his empyema; there were 3 cases of pneumothorax during the acute phase in the "historic" group (P = 0.54). Five children in the urokinase group were debrided and 12 were only drained, as opposed to 9 and 2, respectively, in the "historic" group (P = 0.02). The overall hospital stay was 17 days for the urokinase group, and 24 for the "historic" group (P = 0.02). No bleeding or other major complications were reported in the group treated with urokinase. In conclusion, urokinase treatment does not carry a risk of pneumothorax, while it does reduce hospital stay and the need for pleural debridement.

Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for treatment of extensive intracoronary thrombus: Results from a randomized clinical trial.

BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus-containing lesions are at high risk for adverse events and remain a challenging subset for percutaneous coronary revascularization. Recently, rheolytic thrombectomy with the AngioJet device has been shown to safely remove intracoronary thrombus, but the overall cost-effectiveness of this technique is unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349 patients with overt intracoronary thrombus who were randomly assigned to treatment with intracoronary urokinase (6- to 30-hour infusion followed by definitive revascularization; n = 169) or immediate thrombectomy with the AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2 trial. Catheterization laboratory costs were based on measured resource utilization and 1998 unit costs, whereas all other costs were estimated from hospital charges and cost center-specific cost-to-charge ratios. RESULTS: Compared with urokinase, rheolytic thrombectomy reduced the incidence of periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment reduced procedural costs, hospital room/nursing costs, and ancillary costs with resulting hospital cost savings of approximately $3500 per patient during the initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS: Compared with standard treatment with intracoronary urokinase, rheolytic thrombectomy both improves clinical outcomes and reduces overall medical care costs for patients with extensive intracoronary thrombus.

The efficacy of reteplase in the treatment of thrombosed hemodialysis venous catheters.

Hemodialysis patients frequently require temporary venous catheters until suitable arteriovenous (AV) access can be placed and used for cannulation. However, these temporary catheters often occlude before the AV access has matured. The National Kidney Foundation (NKF) recommends using urokinase to clear the thrombus before progressing to the more invasive and costly procedure of catheter replacement, but urokinase is not currently available. The recombinant tissue-plasminogen activator, reteplase (Retavase, Centocor, Inc., Malvern, PA) was used to clear catheters in 62 patients (a total of 199 doses) at two for-profit outpatient hemodialysis centers with an overall success rate of 91.4% and a minimal cost of $44 per dose. Reteplase was found to be an efficacious and cost-effective alternative to urokinase in the treatment of occluded dialysis venous catheters.

Stability and sterility of recombinant tissue plasminogen activator at -30 degrees C.

We assessed whether frozen recombinant tissue plasminogen activator (rt-PA) remains stable and sterile for up to 22 weeks at -30 degrees C. Our findings confirm that rt-PA is a cost-effective alternative to urokinase for restoring patency to occluded central venous catheters.

Endovascular versus surgical treatment for thrombosed hemodialysis grafts: A prospective, randomized study.

PURPOSE: The objective of this study was to compare clinical outcome and costs for two widely used treatment strategies for hemodialysis graft thrombosis. METHODS: During a 4-year period, 80 patients with thrombosed dialysis grafts were randomly assigned to surgical thrombectomy with or without graft revision (SURG) or thrombolytic therapy with urokinase with the pulse-spray technique (ENDO), with adjunctive percutaneous transluminal angioplasty as indicated. All the procedures were performed in an endovascular operating suite with fistulography. The clinical and cost data were tabulated, and the outcome was analyzed with the life-table method. RESULTS: Fifty-six women and 24 men ranged in age from 33 to 90 years (mean, 63.7 years). The patients had undergone a mean of 2.8 prior access procedures in the ipsilateral extremity. All the grafts were upper extremity expanded polytetrafluoroethylene grafts. Lesions that were presumed to be the primary cause of graft thrombosis were identified in 73 of 80 grafts, and 60 of these were at the venous anastomosis. The procedure time averaged 99 minutes for the patients in the SURG group and 113 minutes for the patients in the ENDO group (P =.12). Eleven patients in the ENDO group crossed over to surgical revision as compared with two patients in the SURG group who required adjunctive percutaneous transluminal angioplasty (P =.005). The mean cost of treatment (including room and supply costs but not professional fees) was significantly higher for the ENDO group than for the SURG group ($2945 vs $1512; P <.001). There were no procedure-related complications in either group. At a median follow-up time of 24 months, there was no difference in primary or assisted primary patency between groups, which averaged 6 and 7 months, respectively. CONCLUSION: Although thrombolytic therapy combined with endovascular treatment can extend the life of dialysis grafts with results similar to surgical revision, there is a high rate of technical failure necessitating surgery and a substantially higher cost for thrombolysis.

Dialysis graft declotting with very low dose urokinase: is it feasible to use "less and wait?".

PURPOSE: "Lyse and wait" dialysis graft declotting is simple and effective, but the minimum necessary dose of urokinase is unknown. The efficacy of the technique with very low dose urokinase is evaluated. MATERIALS AND METHODS: Twenty-one grafts in 17 patients were declotted with use of the lyse and wait technique, but with 5,000-15,000 U of urokinase initially. Graft angiography was performed when an interventional suite was available. Declotting was completed in the manner chosen by the individual operator. Angiograms, interventional radiology records, and dialysis records were reviewed. RESULTS: Technical and clinical success were achieved in 95% of cases. Mean initial urokinase dose was 6,667 U. Initial angiography was performed at a mean 86 minutes. Two cases required second 5,000-U boluses to achieve complete graft thrombolysis. In all other cases, complete or near complete graft thrombolysis was observed with the initial very low dose. No bleeding, arterial embolic, or pulmonary embolic complications were observed. CONCLUSIONS: Doses of urokinase as low as 5,000 U are effective for lyse and wait declotting. A substantial reduction in drug costs can be expected with the "less and wait" modification. Bleeding risk may also be reduced.