Alteplase vs. urokinase for occluded hemodialysis catheter: A randomized trial

Abstract

Introduction Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. To compare the efficacy of alteplase vs. urokinase in reestablishing adequate blood flow through completely occluded vascular catheters. Methods In this randomized study, patients with completely occluded tunneled HD catheters received 40 minutes intracatheter dwell with alteplase (1 mg/mL) or urokinase (5000 IU/mL). Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of ≥250 mL/min. Safety endpoints included the incidence of hemorrhagic and infectious complications. Findings Eligible adult patients (n = 100) were treated with alteplase (n = 44) or urokinase (n = 56). The two groups were similar in gender (male: 51.8% vs. 56.8%, P = 0.35), age (60 ± 12 vs. 59 ± 13 years, P = 0.71), time on dialysis (678 ± 203 vs. 548 ± 189 days, P = 0.77), diabetes and cardiovascular disease (55.6% vs. 70.4%, P = 0.08 and 17.8% vs. 22.7%, P = 0.38, respectively), jugular vein as main vascular access (54.8% vs. 62.5%, P = 0.57), and time of CVC (278 ± 63 vs. 218 ± 59 days, P = 0.67). Primary success with alteplase and urokinase occurred in 42/44 (95%) vs. 46/56 (82%), P = 0.06. Success was not achieved after the second dose of alteplase and urokinase in 1 and 7 cases, respectively (2% vs. 12%, P = 0.075). Serious adverse effects were not observed in both groups. There was no difference between the two groups in infectious complications (P = 0.94). Discussion Alteplase and urokinase are effective thrombolytic agents for restoring HD catheter patency. Our study has revealed a likely slight superiority of alteplase over urokinase for unblocking central lines, but which has enrolled too few patients to be able to detect a difference of this size.

Numerical simulation of blood fluid in hemodialysis catheters and its thrombogenic potential

“…Over time, fibrin sheath attracts platelets and coagulation factors and promotes the adhesion of leukocytes. After weeks or even months, the collagen and smooth muscle are also deposited on the catheter wall, which increases the tissue structure that is bound to the polymer and which will hardly be eliminated with anticoagulants or fibrinolytics (Pollo et al, 2016;Sutherland et al, 2017).…”

“…In clinical practice, non-tunneled CVCs remain a minimum of two months in patients. It would be the usual time required for arteriovenous fistula maturation, however, due to the comorbidities of some patients, such as diabetes, hypertension, coagulopathies, immunological and neurological pathologies, fistulas and grafts may not heal and CVCs make the only blood access during the entire hemodialysis period (Ponce, Mendes, Silva & Oliveira, 2015;Browne, Walshe & Griffin, 2015;Pollo, Dionizio, Bucuvic, Castro & Ponce, 2016).…”

“…In the United States, CVCs are used in up to 15-20% of patients undergoing hemodialysis as a source of vascular access (Pollo et al, 2016). In addition, each year more than 110,000 new patients initiate hemodialysis, 80.2% use CVC as primary vascular access, and 68.3% of them continue to use it after 90 days of stay (Sutherland, Zhang & Charest, 2017).…”

“…The use of CVC may lead to delayed dialysis treatment, increased institutional cost, and the development of adverse events, such as bacterial infections and the development of thrombi with a consequent risk of pulmonary embolism, deep vein thrombosis, and vascular access limitations (Browne et al, 2015;Ponce et al, 2015;Pollo et al, 2016). Studies have indicated that the incidence of CVC occlusion due to the development of thrombi ranges from 5% to 80% in the population undergoing hemodialysis (Premuzic et al, 2018;Shin, Towbin, Zhang, Jhonson & Goldstein, 2017).…”

Eradication of Microorganisms Embedding in Biofilm by a Dose-Dependent Urokinase-Based Catheter Lock Solution in Chronic Hemodialysis Patients

“…Urokinase plasminogen activator (uPA), a thrombolytic enzyme, was first discovered in urine, which converts plasminogen to activated plasmin and lyses fibrin, cause subsequent clot dissolution. As a thrombolytic agent for restoring HD catheter patency, uPA has been prove more effect than heparin and similar to Alteplase [15]. Though, uPA is not recommended as an adjunctive therapy of AML in guidelines.…”