Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

BACKGROUNDCatheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.

METHODSA retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.

RESULTSThe mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.

CONCLUSIONSTreatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

Adolescent ; Adult ; Aged ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Urokinase-Type Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Venous Thrombosis ; drug therapy ; Young Adult

OBJECTIVE: To evaluate the technical aspects and outcomes of endovascular recanalization of a thrombosed native arteriovenous fistula (AVF) complicated with an aneurysm. MATERIALS AND METHODS: Sixteen patients who had a thrombosed AVF complicated with an aneurysm (two radiocephalic and 14 brachiocephalic) were included in this study. Recanalization procedures were performed by mechanical thrombectomy using the Arrow-Trerotola percutaneous thrombectomy device and adjunctive treatments. We evaluated dose of thrombolytic agent, underlying stenosis, procedure time, technical and clinical success, and complications. The primary and secondary patency rates were calculated using the Kaplan-Meier analysis. RESULTS: The thrombolytic agents used were 100000 U urokinase mixed with 500 IU heparin (n = 10) or a double dose of the mixture (n = 6). The thrombi in aneurysms were removed in all but two patients with non-flow limiting residual thrombi. One recanalization failure occurred due to a device failure. Aspiration thrombectomy was performed in 87.5% of cases (n = 14). Underlying stenoses were found in the outflow draining vein (n = 16), arteriovenous anastomosis or juxtaanastomosis area (n = 5), and the central vein (n = 3). Balloon angioplasty was performed for all stenoses in 15 patients. Two patients with a symptomatic central vein stenosis underwent insertion of a stent after balloon angioplasty. Mean procedure time was 116.3 minutes. Minor extravasation (n = 1) was resolved by manual compression. Both technical and clinical success rates were 93.8% (n = 15). The primary patency rates at 3, 6, and 12 months were 70.5%, 54.8%, and 31.3%, respectively. The secondary patency rates at 3, 6, and 12 months were 70.5%, 70.5%, and 47.0%, respectively. CONCLUSION: Thrombosed AVF complicated with an aneurysm can be successfully recanalized, and secondary patency can be prolonged with endovascular treatment.
Aged ; Aged, 80 and over ; Aneurysm/complications/*surgery ; Angioplasty, Balloon ; Arteriovenous Fistula/*surgery ; Arteriovenous Shunt, Surgical/adverse effects ; Constriction, Pathologic/complications ; Endovascular Procedures ; Equipment Failure ; Female ; Fibrinolytic Agents/therapeutic use ; Heparin/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Retrospective Studies ; Stents/adverse effects ; Thrombectomy/instrumentation/*methods ; Thrombosis/etiology/*surgery ; Urokinase-Type Plasminogen Activator/therapeutic use ; Vascular Patency ; Veins

OBJECTIVETo explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths.

METHODSThirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were randomly divided into experimental group and control group. Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group. The catheter function, mean blood flow and venous pressure of dialysis, coagulation, and side effects in the two groups were observed for 6 months.

RESULTSThe rates of catheter dysfunction on the arterial side were 0.65% and 2.71% in the experimental group and control group, respectively (P<0.05), with catheter dysfunction rates on the vein side of 0.92% and 2.41%, respectively (P<0.05). Catheter dysfunction occurred for the first time at 87.9 ± 24.1 days in the experimental group, and at 31.3 ± 11.5 days in the control group (P<0.05). The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion (P>0.05), but was higher in the experimental group at 3 and 6 months after the tube insertion (P<0.05). The mean venous pressure in two groups was similar 1 and 3 months after tube insertion (P>0.05), but was significantly lower in the experimental group at 6 months (P<0.05). Compared with control group, the experimental group showed significantly prolonged prothrombin time (P<0.05) but similar rest coagulation parameters. No serious drug-related side effects occurred in these two groups.

CONCLUSIONEarly use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects.

Catheterization ; adverse effects ; Catheters, Indwelling ; Fibrin ; Humans ; Renal Dialysis ; adverse effects ; Urokinase-Type Plasminogen Activator ; therapeutic use

OBJECTIVETo study the effect of Zhibai Dihuang Pill (ZBDHP) on urokinase-type plasminogen activator (uPA) and sperm quality in ureaplasma urealyticum (Uu) infection infertile patients.

METHODSRecruited were 80 infertility patients with Uu infection at Andriatrics Clinics and Department of Reproduction, including 130 cases of positive Uu semen and 50 cases of negative Uu semen. Patients with positive Uu semen were randomly assigned to the observation group (72 cases) and the control group (58 cases) according to the visit sequence. All patients took antibiotics for 2 weeks. Patients in the observation group additionally took ZBDHP, 6 g each time, twice daily. Those in the control group additionally took Vit E (100 mg each time, twice per day) and ATP (40 mg each time, twice per day). The therapeutic course for all was 90 days. Semen parameters and uPA contents of the sperm membrane were detected and comparatively analyzed.

RESULTSThe sperm membrane uPA content, the sperm motility, the sperm viability, and the percentage of normal morphology sperm in Uu positive infected patients were lower than those in Uu negative infected patients with statistical difference (P < 0.05), but with no significant difference in the sperm density between the two groups (P > 0.05). There was no statistical difference in pre-treatment sperm membrane uPA contents and sperm parameters between the two groups (P > 0.05). Compared with before treatment in the same group, the sperm membrane uPA content, the sperm motility, the sperm viability, and the percentage of normal morphology sperm obviously increased in the two groups with statistical difference (P < 0.05). After treatment, the sperm membrane uPA content increased more obviously in the observation group, with statistical difference when compared with the control group (P < 0.05).

CONCLUSIONSInfection with Uu leads to decreased uPA content of sperm membrance and the sperm motility. ZBDHP could effectively treat Uu infected infertility possibly through fighting against Uu damaged sperm membrane and make the sperm membrane uPA content return to normal, and elevate the fertilizability of sperms.

Anti-Bacterial Agents ; administration & dosage ; pharmacology ; therapeutic use ; Communicable Diseases ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Humans ; Infertility ; Infertility, Male ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Ureaplasma Infections ; drug therapy ; Ureaplasma urealyticum ; drug effects ; Urokinase-Type Plasminogen Activator ; metabolism

BACKGROUNDPulmonary embolism (PE) is a common and often fatal disease. Early after pulmonary thromboembolism, inflammation and associated intimal hyperplasia occur within the pulmonary arteries, similar to what is observed with chronic thromboembolic pulmonary hypertension. This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries.

METHODSSeventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group). Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four rabbits in the PE group were randomly divided into three groups: a control group (treated with normal saline), a low-molecular- weight heparin (LMWH) group (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood gas was analyzed at 2, 7, and 28 days (n = 6 per time point by random group division), then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines, and were stained for intimal hyperplasia.

RESULTSThe overall survival of rabbits undergoing PE was 100%. PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed that alveolar-arterial partial pressure of oxygen (PO2) difference (PA-aO2) significantly increased and PO2 decreased in the control group compared with the sham group. Compared with controls, the UK group had a decreased level of PA-aO2 on day 2 (P < 0.05), however, there was no significant difference in the LMWH group. Compared with controls, the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 (P < 0.05), and the UK group had decreased levels on days 2 and 7 (P < 0.05). Compared with sham group, all PE groups had an increased level of interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) in unaffected lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH group was decreased at all time points compared with controls (P < 0.05). However, TGF-β in affected lung tissue of the LMWH and UK groups increased at day 28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 and 28 in the LMWH group compared with controls; there was no statistical difference in the UK group compared with controls.

CONCLUSIONSUK treatment can rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory benefit. However, LMWH maybe inhibit the later local inflammatory reaction and reduce intimal hyperplasia.

Animals ; Chemokines ; analysis ; Cytokines ; analysis ; Heparin, Low-Molecular-Weight ; therapeutic use ; Male ; Oxygen ; blood ; Pulmonary Artery ; drug effects ; pathology ; Pulmonary Embolism ; drug therapy ; immunology ; Rabbits ; Urokinase-Type Plasminogen Activator ; therapeutic use

BACKGROUNDNo randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI.

METHODSA total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%.

RESULTSIn the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05).

CONCLUSIONSAn intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

Adult ; Aged ; Electrocardiography ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; physiopathology ; Percutaneous Coronary Intervention ; Tyrosine ; analogs & derivatives ; therapeutic use ; Urokinase-Type Plasminogen Activator ; therapeutic use ; Ventricular Function, Left

BACKGROUNDThe recent onset or deterioration of lower extremity ischemia is highly associated with intravascular thrombus. Treatment of these thrombotic occlusions is challenging. Pulse-spray catheter directed thrombolysis (PS-CDT) refers to the technique of intermittent forcefully injecting the thrombolytic agent into the thrombus to fragment it and increase the surface area available for enzymatic action. This study was designed to evaluate the efficacy and safety of PS-CDT in patients with recent onset or deterioration of lower extremity ischemia.

METHODSFrom August 2008 to March 2009, 44 patients with acute or chronic lower extremity ischemia were recruited in this prospective study, which included 37 men and 7 women ranging from 15 to 83 years old (mean age (51.1 ± 17.4) years). PS-CDT through a multi-side-hole thrombolytic catheter by using urokinase was conducted in all patients. The progression of thrombolysis was assessed and graded by angiography. Adjunctive therapies were used to correct underlying lesions. The follow-up period was 12 months.

RESULTSIn the 44 patients, the average total dose of urokinase for each patient was (2 120 000 ± 1 100 000) IU (median 2 000 000 IU), with a median duration of lysis of 48 hours. The rate of initial technical success was 97.7%. The rate of clinically successful lysis was 81.8%. Early (≤ 30 days) and late (from 30 days to 12 months) amputation rates were both 4.5% (2/44). The overall amputation rate was 9.1% (4/44). No mortality was recorded during thrombolysis and follow-up period (12 months). No major bleeding or allergic reaction was seen during thrombolytic therapy. 11.4% had symptoms of distal embolization. The primary patency rate for the arteries that were clinically successfully thrombolyzed as compared with those that failed to lysis was 83.3% vs. 57.1%, respectively, at 1 year.

CONCLUSIONSPS-CDT, combined with adjunctive therapies, is associated with good safety and efficacy in recent-onset or deterioration of lower extremity ischemia. Successful thrombolysis may be accompanied by better outcomes.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Catheterization, Peripheral ; methods ; Female ; Fibrinolytic Agents ; administration & dosage ; therapeutic use ; Humans ; Ischemia ; drug therapy ; Lower Extremity ; pathology ; Male ; Middle Aged ; Peripheral Arterial Disease ; drug therapy ; Thrombolytic Therapy ; methods ; Urokinase-Type Plasminogen Activator ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVETo investigate the indications, safety and efficacy of catheter directed thrombolysis for early left lower extremity deep venous thrombosis (DVT) without vena cava filters protection.

METHODSClinical data of 54 cases of early left lower extremity DVT received catheter directed thrombolysis without vena cava filters from July 2008 to June 2010 were retrospectively analyzed. The thrombosis was entire without free floating clots and no thrombosis in vena cava detected with ultrasound scan. Twenty-five patients were male and 29 were female with the average age of 52.8 years. Fifty-one of which were iliofemoral and popliteal, the other 3 were iliofemoral. The course were ≤ 7 d in 45 cases and these were 8 to 30 d in 9 cases. Urokinase of 300 000 U was infused through catheters per 2 h twice a day. Meanwhile 4000 U of low weight heparin was administered subcutaneously per 12 h, or heparin infusion at dosage of 18 U×kg(-1)×h(-1).

RESULTSThe procedure technically succeeded in all patients. In total cases venous score decreased to 4.6 ± 2.1 post 6 to 10 d of thrombolysis from 10.8 ± 1.0 with thrombolysis rate of 58% ± 18% which was not significantly different between groups of ≤ 7 d and 8 to 30 d (t = 1.02, P = 0.34). On 14(th) day, 11 patients (20.4%) completely recovered, 35 cases (64.8%) experienced large improvement, 8 patients (14.8%) had mild improvement and nobody was failed, resulting in total efficacy of 100%. No patient developed clinical symptomatic pulmonary embolism. SpO2 did not alter markedly post thrombolysis [(91.0 ± 2.6)% vs. (90.8 ± 2.4)%, t = 2.03, P = 0.05]. No patients suffered from cerebral hemorrhage and haemoturia, and catheter induced inflammation occurred in 4 cases (7.41%). There was mild bleeding in puncture sites in 11 patients (20.4%) during the course. There were 36 patients (66.7%) had been followed up with the time of 6 to 21 months. In which 31 cases had no lower extremity edema or had mild edema after activities. Two patients developed serious edema after activities for deep venous insufficiency. Three cases combined with malignant tumor or renal failure recurred.

CONCLUSIONSFor early left extremity DVT which is entire without free floating clots and no thrombosis in vena cava, catheter directed thrombolysis without filter protection maybe administered with safety, efficiency and lower expense.

Catheterization, Peripheral ; Female ; Fibrinolytic Agents ; administration & dosage ; therapeutic use ; Follow-Up Studies ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Pulmonary Embolism ; prevention & control ; Retrospective Studies ; Thrombolytic Therapy ; methods ; Urokinase-Type Plasminogen Activator ; administration & dosage ; therapeutic use ; Vena Cava Filters ; Venous Thrombosis ; complications ; therapy

OBJECTIVETo investigate the clinical value of local regional administration of urokinase and argatroban through small saphenous vein (SSV) catheter in the treatment of acute deep venous thrombosis in the lower limb (LDVT).

METHODSFifty-six patients with acute LDVT were prospectively randomized into the study group (21 cases, 24 limbs) and control group (35 cases, 36 limbs) for treatment with urokinase and argatroban regionally administered via the SSV catheter and with the same agents given via the peripheral vein, respectively. The patients were examined for changes in serum fibrinogen (FBG) and D-dimer and the perimeter of the affected limbs, and the complications in relation to the agents were observed.

RESULTSBy corrected Chi-square test, the incidence of complications was significantly lower in the study group than in the control group (1/21 vs 4/36, χ(2)=1.92, P≤0.05). Wilcoxon's sign rank test suggested no statistically significant difference between the two groups in the total effective rate (95.8% vs 94.4%, V=0.52, P>0.05), but the total excellent rate differed significantly between them (83.3% vs 55.6%, V=2.36, P≤0.05). Serum FBG underwent no significant variations in the study group during thrombolysis (P>0.05), but decreased significantly in the control group (P≤0.05). The decreases in serum D-dimer and perimeter of the affected limbs occurred earlier in the study group than in the control group (P≤0.05).

CONCLUSIONRegional administration of urokinase and argatroban via small saphenous vein catheter can promote the thrombolytic effect and reduce the risk of hemorrhage in the treatment of LDVT.

Adult ; Female ; Fibrinolytic Agents ; Humans ; Injections, Intravenous ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Pipecolic Acids ; administration & dosage ; therapeutic use ; Saphenous Vein ; Urokinase-Type Plasminogen Activator ; administration & dosage ; therapeutic use ; Venous Thrombosis ; drug therapy ; Young Adult