Objective To investigate the efficacy, influencing factors and thrombolytic regimen of local urokinase thrombolysis in the treatment of arteriovenous endovascular fistula thrombosis in hemodialysis patients. Methods In 28 hemodialysis patients with arteriovenous endovascular fistula thrombosis, local percutaneous injection of urokinase was administered with an average of (49.82±25.46) million u for local thrombolysis. Before and after treatment, vascular color ultrasonography was performed, liver and kidney function, prothrombin time (PT) and plasma fibrinogen (Fib) were measured, and adverse effects were observed. Results A total of 44 thrombolytic treatments were performed in 28 patients, and 32 cases were thrombolized (72.7%). The time to thrombosis was significantly shorter in the thrombolysis cases than in the thrombolysis failure group, and the incidence of wall thrombosis was significantly higher in the thrombolysis failure group than in the thrombolysis group. Re-embolization occurred in 53.13% of patients in the thrombolysis group. The incidence of re-embolization in the thrombolysis group was related to the appendage thrombus and the original disease, and the incidence of re-embolization was higher in diabetic patients than in non-diabetic patients. In the lysis group, the number of urokinase dosage ≤ 600,000 u reached 81.3%, and the number of embolism ≤ 36 h was 96.9%, and one case was lysed after 72 h. In the lysis group, two cases were re-embolized 16-48 h after lysis, and were re-embolized after urokinase drip was given again. The common side effects of urokinase thrombolysis were subcutaneous bleeding, epistaxis and gingival bleeding, the incidence of which was very low, and no serious complications such as gastrointestinal and cerebral bleeding were seen. Conclusion Urokinase lysis of dialysis access thrombus is simple and less invasive, with a success rate as high as 72.7%, and has high clinical application value, and no serious complications such as gastrointestinal bleeding and cerebral embolism were seen. The effect of thrombolysis is related to the time of thrombus formation, the presence or absence of attached thrombus and diabetes mellitus. The amount of urokinase used for thrombolysis should not exceed 600,000 u. The timing of thrombolysis should be selected within 24 h of internal fistula embolization and not more than 36 h. The observation time of thrombolysis should be more than 72 h. Urokinase and low molecular heparin maintenance therapy after thrombolysis can prevent re-embolism after thrombolysis. [Keywords] Urokinase, arteriovenous endovascular fistula, thrombolysis, thrombosis, arteriovenous endovascular fistula thrombosis is the main cause of arteriovenous endovascular fistula failure in hemodialysis patients. In the past, the treatment mostly used arteriovenous endovascular fistula dissection and embolization, and then arteriovenous endovascular fistuloplasty, which had clear efficacy but caused great damage to the vessels and many abandoned vessels. In recent years, percutaneous catheter thrombolysis, embolization with balloon catheter, endoluminal angioplasty and stenting have been developed to treat arteriovenous fistula thrombosis [1, 2], which is less invasive and more effective, but more costly and complicated. Since the 1980s, the use of local injection of urokinase for the treatment of arteriovenous fistula thrombosis has been reported in the literature, but the results and treatment protocols have been inconsistent [3, 4, 5], and the prognosis and follow-up treatment protocols have been rarely reported. In this paper, we reviewed and analyzed the clinical data of 44 cases of arteriovenous endovascular fistula thrombosis in 28 hemodialysis patients admitted to our hospital from January 2002 to February 2007 and treated with local injection of urokinase for thrombolysis to investigate the efficacy, amount of urokinase required for thrombolysis, prognosis, influencing factors and treatment plan of local injection of urokinase for arteriovenous endovascular fistula thrombosis. Subjects and methods I. Subjects 28 patients with arteriovenous endovascular thrombosis treated with local urokinase were all maintenance hemodialysis patients in our hospital. 44 cases of endovascular thrombosis were recorded, all of which were diagnosed by vascular ultrasound and clinical confirmation. The diagnostic criteria for endovascular thrombosis [2]: clinical auscultation of endovascular murmur, palpation without palpable tremor, interruption of blood flow on ultrasound, and endovascular thrombosis. 28 patients had no active bleeding or bleeding tendency, no active liver disease, no severe hypertension, and blood pressure maintained at 94-180/65-100 mmHg. II. Methodology Method of endovascular thrombosis: 100,000 u of urokinase was added to 10 ml with saline. Then use 500,000 u urokinase + saline to 50 ml with a micropump at a rate of 3-5 million u/h. If the local pressure at the internal fistula is too large and the patient has obvious pain, the needle can be replaced with a needle at 2.0 cm above the thrombus at the venous end, with the tip pointing to the internal fistula side; every If 500,000 urokinase is pumped in, 500,000 urokinase will be pumped in, and after 24 hours of pumping, 100,000 urokinase/d will be given for 7 days, while 40 mg of low molecular heparin will be injected subcutaneously for 12 hours, and after 3 days, it will be changed to 40 mg of low molecular heparin/d for a total of 5-7 days. If there is no lysis after 500,000u urokinase pump, urokinase 100,000u/d should be given after 24h for 1-3 days, and low molecular heparin 40mg/12h for 3 days, if still no lysis, the drug should be stopped. Criteria for thrombolysis of endovascular fistula: murmur can be heard, tremor can be palpated, continuous blood flow through endovascular fistula can be seen by vascular ultrasound, at least one dialysis can be completed after thrombolysis, and blood flow is above 180 ml/min. Diagnostic criteria for failure of thrombolysis of endovascular fistula: 1, 100,000 urokinase intravenous push and 500,000 urokinase pumping is still not lysed, then 24h later, 100,000 urokinase/d IV for 1-2 days, at the same time, low molecular heparin 40mg/12h is used until 3 days, still no vascular murmur is heard at the endovascular fistula, no continuous blood flow through the endovascular fistula on ultrasound; 2, although no vascular murmur is heard at the endovascular fistula, there is continuous blood flow through the endovascular fistula on ultrasound. The blood flow in the fistula was below 150 ml/min during dialysis. In both cases, the endovascular fistula failed to thrombolize. III. Statistical analysis The measurement data were expressed as mean ± standard deviation (`x±s), t-test was used for comparison between groups, t’ test was used for approximation method for two small samples with uneven variance, and exact probability calculation method and statistical description method were used for comparison of counting data, with 4 cases of subcutaneous hematoma above P600,000u and 2 cases of epistaxis and 1 case of gingival bleeding, no gastrointestinal bleeding and serious complications such as cerebral hemorrhage. The details are shown in Tables 1 and 2. The time used for urokinase thrombolysis: 68.8% of cases were lysed within 12h, 75.0% within 24h, 84.4% within 36h, only 1 new case was lysed between 36 and 48 hours, 3 cases (9.4%) were increased between 48 and 60h, no new cases were lysed between 60 and 72h, and only 1 case (3.4%) was increased above 72h. There was only one case (3.1%) increase in the number of lysis cases over 72 hours. Since the half-life of urokinase is 15 minutes and the effect basically disappears after 24 hours, this group chose to continue to give urokinase 100,000 u + 100 ml of saline 24 hours after the end of pumping urokinase to consolidate the efficacy and prevent the formation of thrombus again after lysis. In this group, there was one case in which the urokinase dosage reached 900,000 u, and the thrombolysis time was still not dissolved until 72 h. After stopping urokinase and low molecular heparin for 1 day (97 h), the thrombolysis was dissolved. In four cases, urokinase and low molecular heparin were discontinued after secondary lysis with urokinase, and in one case, the embolus was re-embolized 16 h after lysis, and the patient was re-embolized after urokinase drip was given again. Among the 24 cases treated with urokinase and low molecular heparin after lysis, only one case was re-embolized 48 h after lysis and was recanalized after urokinase drip. See Table 3. Prognosis and influencing factors Fifteen of the 32 patients with lysis have not re-embolized since lysis, and 17 cases have re-embolized (53.1%). The time to re-embolization ranged from 0.25 to 26 months after lysis, with a mean of 7.375±9.24 months. Among the 32 embolization cases, urokinase thrombolysis was performed within 24 h of embolization in 30 cases (93.8%), and only 1 case (3.1%) was thrombolysed at 24-36 h of embolization, and no case was thrombolysed at 36-48 h of embolization. The thrombus formation time in the thrombolysis group was significantly shorter than that in the failed thrombolysis group. The incidence of wall thrombosis in the thrombolysis failure group was significantly higher than that in the thrombolysis group. The incidence of re-embolism in the thrombolysis group was related to the appendage thrombus and the original disease, and the incidence of re-embolism was higher in diabetic patients than in non-diabetic patients. See Tables 4 and 5. Discussion Since foreign scholars first reported the application of urokinase thrombolysis for endovascular thrombosis in the early 1980s, there have been successive reports in the literature on the local application of urokinase thrombolysis for arteriovenous endovascular thrombosis, with success rates ranging from 30% to 70% [3, 4, 5]. Urokinase is a serine protease secreted by human renal tubular epithelial cells, which can specifically cleave the peptide bond between arginine at position 560 and valine at position 561 in plasma fibrinogen, activating fibrinogen and converting it into fibrinolytic enzyme, thus hydrolyzing fibrin and causing thrombus lysis, with a half-life of 15 minutes, and the effect basically disappears after 24 hours. In recent years, some scholars in China have reported the local application of urokinase thrombolysis in the treatment of arteriovenous fistula thrombosis [6, 7], with clear effects, but few studies on the dose of urokinase used for thrombolysis, time used for thrombolysis, influencing factors, re-embolization and prognosis have been reported. In this study, we reviewed and analyzed the clinical data of 28 cases of 44 cases of percutaneous local urokinase thrombolysis for arteriovenous fistula thrombosis, and the results showed that the effect of percutaneous local urokinase thrombolysis for arteriovenous fistula thrombosis was clear, and 32 of 44 thrombolysis cases were lysed, with a lysis rate of 72.7%. In the thrombolysis group, the number of thrombolysis cases with urokinase dosage ≤500,000 u and ≤600,000 u accounted for 71.9% and 81.3% of the total thrombolysis cases, respectively, while only 18.7% and 8.6% of the cases were recanalized when thrombolysis with urokinase continued to 700,000 and 800,000 u. The common complication of percutaneous local urokinase thrombolysis for arteriovenous fistula thrombosis is subcutaneous hematoma. 6 cases of subcutaneous bleeding occurred in 44 cases of thrombolysis in this group, among which 4 cases of subcutaneous hematoma, 2 cases of epistaxis and 1 case of gingival bleeding occurred in urokinase dosage above 600,000 u, indicating that the incidence of subcutaneous hematoma, epistaxis and gingival bleeding increased with the increase of urokinase dosage and thrombolysis time. No serious complications such as gastrointestinal bleeding were observed in this group. Previous literature reported that the thrombolytic dose of urokinase was mostly between 250,000 and 500,000 u. However, the present data showed that only 34.4-71.9% of the cases were successfully thrombolized at the dose of urokinase between 250,000 and 500,000 u, which is different from the literature [8, 9]. Therefore, this study recommends that the dose of urokinase used for thrombolysis of arteriovenous fistula embolism should not exceed 600,000 u from the results of thrombolytic effect and side effects, and the complications caused by increasing the dose of urokinase can be avoided. Among the 32 patients with thrombolysis, 75.0% were thrombolysed within 24 h, 84.4% were thrombolysed within 36 h, and only one case was thrombolysed between 36 and 48 h. According to the method of thrombolysis in this study, the amount of urokinase used in 17.2-41.5 h was 600,000 u, and the amount of urokinase used in 48-65.5 h was 700,000 u. In other words, the lysis rate was 75.0% at the dosage of 600,000 u at 24 h. The amount of urokinase used at 36 h did not increase, but the number of lysis cases increased to 84.4%, suggesting that in patients with chronic renal failure The prolonged metabolism time of urokinase in patients with chronic renal failure and the continued effect of urokinase after discontinuation of urokinase may have led to an increase in the number of lysis cases between 24 and 36 h without increasing the amount of urokinase. Therefore, it is recommended that the duration of urokinase thrombolysis be controlled at 36h, and the amount of urokinase used at 36h was 600,000 u, which is consistent with the above recommended dose. The literature reports that the effect of urokinase does not intensify with increasing dose [4], and the results of this paper differ from those reported in the literature. There was one case of lysis after 72 h in our data, therefore, it is recommended that urokinase lysis should be observed for more than 72 h. It is also advisable to use temporary vascular access dialysis to avoid damage to the newly lysed endovascular fistula by puncture. In our data, there was one case in which the urokinase dosage to 900,000 u was still not passed, and after stopping urokinase and low-molecular heparin for 1 day, it was lysed in the 97th hour, suggesting that there were individual differences in the patients’ response to urokinase. Previous literature reported that urokinase and low molecular heparin were discontinued after lysis [2, 6, 7], but in our study, urokinase and low molecular heparin were discontinued after lysis with urokinase in 4 cases, and one of them was embolized again 16 h after lysis, and was recanalized after urokinase drip; while only one of the 24 cases treated with urokinase and low molecular heparin after lysis was recanalized 48 h after lysis, and was recanalized after urokinase drip. This indicates that maintenance treatment with urokinase and low-molecular heparin after lysis is necessary to prevent re-embolization immediately after lysis, therefore, it is recommended that consolidation treatment with urokinase should be continued after lysis. In our data, we chose to continue urokinase 100,000 u + saline 100 ml for 7 days and low molecular heparin for 3 days 24 h after the end of urokinase pumping to consolidate the efficacy and prevent the re-embolization in the lysed cases. In 32 cases, 93.8% of the total cases were thrombolized within 24 h of embolization, and 1 case (3.1%) was thrombolized at 36 h of embolization, and no new cases were thrombolized at 36-48 h of embolization. Therefore, it is recommended that the timing of endovascular thrombolysis should preferably be within 24 h of endovascular embolization, and at most not more than 36 h. Local urokinase thrombolysis alone is not recommended for patients with endovascular embolization for more than 36 h. The analysis of factors influencing the thrombolytic effect showed that the thrombolytic effect was independent of the time of endovascular fistula use, age, gender, and dialysis duration. Diabetic hemodialysis patients accounted for 76.47% of arteriovenous endovascular fistula re-embolization cases and 26.67% of non-re-embolization cases, indicating that diabetic dialysis patients are a high risk factor for arteriovenous endovascular fistula embolization and are prone to re-embolization after lysis with poor prognosis. In our data, 53.13% of the lysed cases showed re-embolization, indicating that re-embolization can occur after lysis of arteriovenous fistula embolism and the incidence of re-embolization is high. Of the 32 successful thrombolysis cases, 19 cases were confirmed to have wall thrombosis, and 13 of them had re-embolism after lysis (68.42%), while only 3 of the 13 cases without wall thrombosis had re-embolism (23.08%), so the incidence of re-embolism after lysis was significantly higher in patients with wall thrombosis than in patients without wall thrombosis (P