Endovascular thrombectomy and intra-arterial interventions for acute ischaemic stroke.

BACKGROUND: Most disabling strokes are due to a blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called endovascular interventions can cause bleeding in the brain. This is a review of randomised controlled trials of endovascular thrombectomy or intra-arterial thrombolysis, or both, for acute ischaemic stroke. OBJECTIVES: To assess whether endovascular thrombectomy or intra-arterial interventions, or both, plus medical treatment are superior to medical treatment alone in people with acute ischaemic stroke. SEARCH METHODS: We searched the Trials Registers of the Cochrane Stroke Group and Cochrane Vascular Group (last searched 1 September 2020), CENTRAL (the Cochrane Library, 1 September 2020), MEDLINE (May 2010 to 1 September 2020), and Embase (May 2010 to 1 September 2020). We also searched trials registers, screened reference lists, and contacted researchers. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any endovascular intervention plus medical treatment compared with medical treatment alone in people with definite ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors (MBR and MJ) applied the inclusion criteria, extracted data, and assessed trial quality. Two review authors (MBR and HL) assessed risk of bias, and the certainty of the evidence using GRADE. We obtained both published and unpublished data if available. Our primary outcome was favourable functional outcome at the end of the scheduled follow-up period, defined as a modified Rankin Scale score of 0 to 2. Eighteen trials (i.e. all but one included trial) reported their outcome at 90 days. Secondary outcomes were death from all causes at in the acute phase and by the end of follow-up, symptomatic intracranial haemorrhage in the acute phase and by the end of follow-up, neurological status at the end of follow-up, and degree of recanalisation. MAIN RESULTS: We included 19 studies with a total of 3793 participants. The majority of participants had large artery occlusion in the anterior circulation, and were treated within six hours of symptom onset with endovascular thrombectomy. Treatment increased the chance of achieving a good functional outcome, defined as a modified Rankin Scale score of 0 to 2: risk ratio (RR) 1.50 (95% confidence interval (CI) 1.37 to 1.63; 3715 participants, 18 RCTs; high-certainty evidence). Treatment also reduced the risk of death at end of follow-up: RR 0.85 (95% CI 0.75 to 0.97; 3793 participants, 19 RCTs; high-certainty evidence) without increasing the risk of symptomatic intracranial haemorrhage in the acute phase: RR 1.46 (95% CI 0.91 to 2.36; 1559 participants, 6 RCTs; high-certainty evidence) or by end of follow-up: RR 1.05 (95% CI 0.72 to 1.52; 1752 participants, 10 RCTs; high-certainty evidence); however, the wide confidence intervals preclude any firm conclusion. Neurological recovery to National Institutes of Health Stroke Scale (NIHSS) score 0 to 1 and degree of recanalisation rates were better in the treatment group: RR 2.03 (95% CI 1.21 to 3.40; 334 participants, 3 RCTs; high-certainty evidence) and RR 3.11 (95% CI 2.18 to 4.42; 268 participants, 3 RCTs; high-certainty evidence), respectively. AUTHORS' CONCLUSIONS: In individuals with acute ischaemic stroke due to large artery occlusion in the anterior circulation, endovascular thrombectomy can increase the chance of survival with a good functional outcome without increasing the risk of intracerebral haemorrhage or death.

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

BACKGROUND: The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study. METHODS: Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function. RESULTS: 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis. CONCLUSIONS: Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Efficacy of modified pressure cuff for thrombolytic treatment on lower extremity deep venous thrombosis.

ABSTRACT: To compare the effectiveness and patient comfort between two methods that block superficial venous blood flow during the thrombolytic treatment of lower extremity deep venous thrombosis (DVT) to provide evidence that informs clinical choice.One hundred twenty patients with lower extremity DVT were randomly divided into sphygmomanometer (group A, n = 40), tourniquet (group B, n = 40), and control group (no blocking, n = 40). All the patients were treated with a daily dosage of urokinase using a dial sphygmomanometer cuff and tourniquet to block lower extremity superficial vein blood flow. The pressure of the dial sphygmomanometer blocking lower extremity superficial vein blood flow was measured during lower extremity venography. Leg swelling reduction rate, venous patency, thrombus removal rate, and average comfort index were observed during the blocking process.The average pressure value for group A was 70  ±â€Š10 mm Hg. The differences in the swelling reduction rate and venous patency were significant between the groups. Comparing the two groups at different time points, the average thrombus clearance rate of group A was higher than that of group B and control group. The leg pain scores of group A were lower than those of group B and control group. The postoperative comfort ratio of group A was higher than that of group B, and the proportion of severe discomfort in group A was lower than that in group B.Compared with the tourniquet, using a dial sphygmomanometer cuff to block lower extremity superficial vein blood flow achieved a better thrombolytic effect on DVT and provided higher patient comfort during treatment.

Multiple arterial and venous thromboembolism in a male patient with hereditary protein C deficiency: A case report.

RATIONALE: Hereditary protein C deficiency has a high prevalence in Asian populations, being the important risk factor associated with thrombophilia. Traditionally, conservative medication is the first choice for patients with hereditary protein C deficiency. However, there are few reports on whether aggressive surgical treatment can be performed when patients continue to develop life-threatening ischemic symptoms after adequate anticoagulant and thrombolytic therapy. PATIENT CONCERNS: A 40-year-old male presented with right lower extremity pain for 1 week. DIAGNOSIS: Computed tomography angiography (CTA) of lower extremity indicated arterial embolization of the right superficial femoral artery. Vascular ultrasonography showed old extensive thrombus in the deep vein of the left lower extremity. Electrocardiogram reported old anterior myocardial infarction. Sequencing of the gene encoding protein C (PROC) gene revealed that a heterozygous in-frame deletion mutation (c.577-579delAAG, p.192delK). Based on these findings, the diagnosis of hereditary protein C deficiency was made. INTERVENTIONS: The patient was given low-molecular-weight heparin (LMWH) anticoagulation and urokinase treatment immediately. Then we performed the Fogarty catheter embolectomy with about 18.5 cm thrombus being removed and utilized the balloon catheter to dilate the anterior tibial artery. Despite given adequate anticoagulant and thrombolytic therapy postoperatively, the patient still had new thrombosis, and eventually underwent arterial embolectomy and amputation. OUTCOMES: The patient was discharged with good wound healing and continued rivaroxaban treatment at a dose of 20 mg daily. The patient was followed-up monthly until 1 year: there was no adverse ischemic events occurred. LESSONS: Aggressive surgical treatment may be the effective attempt for life-saving when conservative treatment as the first choice had unsatisfactory results in hereditary protein C deficiency patients. The novel oral anticoagulants (NOACs) could be more suitable than warfarin for the treatment and prevention of recurrence in patients with hereditary protein C deficiency.

Treatment challenges in patients with early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery: A case report.

INTRODUCTION: Early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery is one of the most fatal surgical complications. It is often accompanied by shock and hypotension, with high mortality rate. Due to surgical wounds, patients with early acute massive PTE after lung cancer surgery have a high risk of thrombolytic bleeding, which renders treatment more challenging and there is currently no standard protocol on how to safely and effectively treat these patients in the clinic. PATIENT CONCERNS: A 66-year-old woman after video-assisted thoracoscopic surgery for lung cancer, experienced sudden severe dyspnea, shock and hypotension with high D-Dimer, changed electrocardiogram (ECG), right ventricular dilatation, severe tricuspid regurgitation, and raised pulmonary arterial pressure on ultrasonic cardiogram (UCG), thromboses found on Ultrasonography of lower extremity vein. DIAGNOSIS: Because of her clinical manifestations and results of bedside auxiliary examinations, the patient was finally diagnosed with acute high-risk PTE after lung cancer surgery. INTERVENTIONS: 1.5 hours after onset of symptoms, thrombolysis using a continuous micropump infusion of 20,000 units/kg urokinase into the peripheral vein for 2 hours was initiated for this patient. OUTCOMES: The patient died of massive hemorrhage after thrombolysis. LESSONS: Treatment for patients with early acute PTE after lung cancer surgery is challenging due to a high risk of thrombolytic bleeding at the surgical site. Real-time monitoring of vital signs during thrombolysis and catheter-directed thrombolysis are recommended for these patients, in order to use the minimum drug dosage for quick curative effects and a low risk of bleeding.

Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study.

INTRODUCTION: Patients at intermediate-high risk of developing a pulmonary embolism (PE) are very likely to experience adverse outcomes, such as cardiovascular instability and death. The role of thrombolytic therapy in intermediate-high-risk PE remains controversial. OBJECTIVES: This study aimed to determine the efficacy and safety of low-dose urokinase (UK) thrombolytic therapy for intermediate-high-risk PE. PATIENTS AND METHODS: This retrospective study included 81 consecutive patients with intermediate-high-risk PE from two centers. Patients received low-dose UK or low-molecular-weight heparin (anticoagulant therapy group). The efficacy outcomes were mortality, computed tomography pulmonary angiography (CTPA)-confirmed absorption, and dyspnea. Safety was assessed as the incidence of bleedings. RESULTS: The in-hospital mortality, 9-month mortality, and long-term mortality at the last follow-up were comparable for the low-dose UK group and the anticoagulant therapy group (6.45% vs. 0%, p = 0.144, 9.68% vs. 8.16%, p = 0.815, and 12.90% vs. 12.24%, p = 0.931, respectively). CTPA-confirmed absorption at one month after admission was higher in the low-dose UK group than in the anticoagulant therapy group (p = 0.016). The incidences of short-term dyspnea at discharge and long-term dyspnea at the last follow-up were lower in the low-dose UK group than in the anticoagulant therapy group (27.59% vs. 52%, p = 0.035, 33.33% vs. 58.14%, p = 0.043, respectively). No major bleeding occurred. The incidence of minor bleeding was not significantly different between the two groups (3.23% vs. 6%, p = 0.974). CONCLUSION: In intermediate-high-risk PE, a low-dose UK might increase CTPA-confirmed absorption and improve short-term and long-term dyspnea without affecting mortality or increasing the bleeding risk.

Fibrinolytic-Facilitated Chronic Subdural Hematoma Drainage-A Systematic Review.

BACKGROUND: The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative catheter drainage. Although generally effective, these treatments have continued to be complicated by recurrence, especially in partially hemolyzed or septated hematomas. Recently, interest in the use of fibrinolytic agents as an adjunct to surgical treatment to address this limitation has been increasing. We conducted a systematic review, focusing on the efficacy and safety profile of fibrinolytic agents and compared the different fibrinolytic agents. METHODS: The PubMed, EMBASE, CINAHL Plus, and Cochrane Library databases were searched for trials relevant to fibrinolytic administration in the treatment of CSDH. The findings are reported in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The data from 1702 subjects from 6 retrospective observational studies were qualitatively analyzed. In addition, we included 11 case series and reports for discussion. RESULTS: For 1449 patients, the use of urokinase or tissue plasminogen activator improved hematoma drainage and shortened the hospital stay (7.04 days), with an overall hematoma recurrence rate of 1.59%. The incidence of infection, seizure, and intracranial bleeding was 3.18%, 0.80%, and 0.41%, respectively, which compared favorably with previously reported findings for surgical drainage without the use of fibrinolytic agents. CONCLUSIONS: The routine use of intrathecal urokinase and tissue plasminogen activator could be a new direction in the management of CSDH. Conclusive clinical evidence is lacking, however, and further prospective controlled studies are warranted to confirm the benefit and safety of this treatment strategy and to identify the optimal agent and dosing regimen.

Clinical efficacy of one-stage thrombus removal via contralateral femoral and ipsilateral tibial venous access for pharmacomechanical thrombectomy in entire-limb acute deep vein thrombosis.

OBJECTIVE: In the present study, we compared the early results between different approaches for pharmacomechanical thrombectomy (PMT) in the treatment of entire-limb acute deep vein thrombosis (DVT). METHODS: The present retrospective cohort study included patients with entire-limb acute DVT who had undergone PMT from January 2016 to March 2019 at two independent vascular centers. At the first center (Renji Hospital), the vascular surgeons used contralateral femoral venous access or ipsilateral tibial venous access (CFVA/ITVA). All consecutive patients with entire-limb acute DVT had undergone PMT through CFVA/ITVA at the first center. At the second center (Affiliated Hangzhou First People's Hospital), the vascular surgeons had conducted PMT using the traditional approach via ipsilateral popliteal venous access (IPVA). All consecutive patients had undergone PMT through IPVA at the second center. The primary endpoint was the incidence of post-thrombotic syndrome (PTS). The secondary endpoints included thrombus removal grade, venous primary patency rate, and the incidence of moderate-to-severe PTS. RESULTS: A total of 73 patients were enrolled in the present study, including 37 patients with CFVA/ITVA at the first center and 36 patients with IPVA at the second center. No significant difference was detected between the two groups in age, gender, onset time, affected limb, or risk factors. The proportion of patients who had undergone catheter-directed thrombolysis was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .010). Thrombus removal grade III was achieved more often in the CFVA/ITVA group than in the IPVA group (P = .007). The PTS incidence was significantly lower in the CFVA/ITVA group than in the IPVA group (P = .043). The thrombus removal grade and access type were independent factors associated with the development of PTS. Patients with complete thrombus removal (grade III) and CFVA/ITVA had a significantly lower incidence of PTS. CONCLUSIONS: PMT can increase the thrombus clearance rate, reduce the requirement for subsequent catheter-directed thrombolysis, and, potentially, decrease the incidence of PTS using CFVA/ITVA instead of traditional IPVA in the treatment of entire-limb acute DVT.

Clinical Efficacy of Prodom-Assisted Urokinase in the Treatment of Male Infertility Caused by Impaired Semen Liquefaction.

PURPOSE: To evaluate the clinical efficacy of prodom in the administration of urokinase in the vagina in couples with impaired semen liquefaction. MATERIALS AND METHODS: Overall, 261 patients with impaired semen liquefaction were randomly divided into prodom-assisted urokinase treatment (PAUT) group (n = 91), syringe-assisted urokinase treatment (SAUT) group (n = 86), and traditional treatment (TT) group (n = 84) in the first stage. If the first stage of treatment failed, other treatment methods were initiated instead and the patients were grouped according to the newer treatment method in the second stage. The pregnancy rate, time-to-conception, and treatment costs were evaluated in each group. RESULTS: In the first stage, the pregnancy rate in the PAUT, SAUT, and TT groups was 69.23%, 29.07%, and 22.62%, respectively; the time-to-conception was 2.66 ± 1.44, 3.69 ± 2.61, and 3.86 ± 3.00 months, respectively; the treatment costs were 658.18 ± 398.40, 666.67 ± 507.50, and 680.56 ± 480.94 $, respectively. The pregnancy rate and time-to-conception were different in the PAUT group compared with those in SAUT and TT groups (all P < 0.05). However, the difference in treatment costs was not significant (P = 0.717). In the second stage, 154 nonpregnant patients were divided into nine treatment groups, and the effects of changing TT to PAUT on the pregnancy rate, time-to-conception, and treatment costs were observed to be different from those of other treatments (all P < 0.05). CONCLUSION: Prodom-assisted urokinase can effectively treat male infertility secondary to impaired semen liquefaction.

Delayed pulmonary embolism after unicompartmental knee arthroplasty: A case report.

INTRODUCTION: Although venous thromboembolism (VTE) is relatively rare after unicompartmental knee arthroplasty (UKA), symptomatic pulmonary embolism (PE) can be fatal. Whether routine thromboprophylaxis or thrombolytic treatment is necessary for patients undergoing UKA remains unclear. Here, we present a case of delayed pulmonary embolism after UKA. PATIENT CONCERNS: A 57-year-old women underwent cemented UKA for left localized medial knee pain. There were no risk factors of VTE besides high BMI before surgery. 2 months after surgery, the patient presented with dyspnea and palpitation, and these symptoms could not be alleviated after rest. DIAGNOSIS: An arterial blood gas analysis showed decreased PO2, SO2 and PCO2. Pulmonary CTA showed multiple pulmonary embolism in the trunk of the right lower pulmonary artery and the branch of the left lower pulmonary arteries. The final diagnosis was delayed pulmonary embolism after UKA. INTERVENTIONS: Urokinase thrombolysis was administered intravenously. Low molecular weight heparin and warfarin were prescribed for anticoagulation. OUTCOMES: The patient's symptoms abated, and chest CTA showed that the pulmonary embolism had dissolved. No further thrombosis has been observed for more than 6 years. CONCLUSIONS: We presented an unusual case of delayed pulmonary embolism after UKA. Despite the low incidence, its life-threatening nature makes it imperative for surgeons to be well-informed about thrombosis and pay more attention to its prevention strategies.

Outcome of AngioJet mechanical thrombus aspiration in the treatment of acute lower extremities deep venous thrombosis.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety in patients with acute lower extremity deep venous thrombosis who underwent pharmacomechanical thrombectomy (PMT, AngioJet mechanical thrombus aspiration). METHODS: In this retrospective, 424 consecutive patients with acute lower extremity deep venous thrombosis from three institutions were enrolled in the study from January 2015 to December 2018. Of these, patients were divided into two groups, AngioJet group (n = 186) and catheter-directed thrombolysis (CDT) group (n = 238). Evaluation indexes including limb circumference difference, length of stay (LOS), urokinase dosage, periprocedural complications, follow-up imaging findings and villalta scores were analyzed from the medical records. RESULTS: A total of 424 patients diagnosed with acute lower extremity deep venous thrombosis were collected in this study. These patients were categorized into AngioJet group and CDT group. Significant differences were observed between the two groups with respect to the thigh circumference difference (5.32 ± 1.85 cm vs. 4.69 ± 2.15 cm; p = 0.04), calf circumference difference (2.79 ± 1.54 cm vs. 2.35 ± 1.25 cm; p = 0.01), thigh detumescence rate (72.19 ± 19.55% vs. 65.35 ± 17.26%; p = 0.00) and calf detumescence rate (62.79 ± 18.56% vs. 55.75 ± 17.27%; p = 0.00). The mean dose of urokinase in AngioJet group was 95.16 ± 45.89 million IU significantly less than that in the CDT group 293.76 ± 42.71 million IU (p = 0.00). The overall bleeding complication rate was 9.91% (19 patients in AngioJet group and 23 patients in CDT group), which included three major (0.71%, 3/424) and 39 minor (9.2%,39/424) events. In the AngioJet group, serum creatinine (sCr) concentration and urine erythrocyte from the hemolysis caused by the mechanical process were higher than baseline data at admission (p = 0.00, p = 0.00). The postoperative red blood cell and hemoglobin in two groups were lower than baseline data (p = 0.00, p = 0.00). Compared with CDT, AngioJet thrombectomy has significantly lower estimated incidence of PTS in the follow-up. CONCLUSION: AngioJet thrombectomy has stronger clearance ability for acute lower extremity deep venous thrombosis leading to significant reduction in the consumption of hospital resources, total dose of thrombolytic agents, and infusion time, thereby preventing adverse bleeding events, but patients with renal insufficiency should be careful. Ideal short-term and medium-term efficacy and safety are certain.

Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5 years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.

Safety and efficacy study of prourokinase injection during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction.

OBJECTIVES: To evaluate the efficacy and safety of intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions in patients with acute ST-segment elevation myocardial infarction. METHODS: Acute ST-segment elevation myocardial infarction patients underwent primary percutaneous coronary interventions were randomly divided into two groups: intracoronary prourokinase group (n = 125) and control group (n = 135). During primary percutaneous coronary interventions, prourokinase or saline was injected to the distal end of the culprit lesion via balloon catheter after balloon catheter dilatation. Demographic and clinical characteristics, infarct size, myocardial reperfusion, and cardiac functions were evaluated and compared between two groups. Hemorrhagic complications and major averse cardiovascular events (MACE) occurred in the 6-months follow-up were recorded. RESULTS: No significant differences were observed between two groups with respect to baseline demographic, clinical, and thrombolysis in myocardial infarction grade (P > 0.05). In the intracoronary prourokinase group, more patients had ST-segment resolution (>50%) compared with control group (P < 0.05). Patients in the intracoronary prourokinase group showed lower levels of serum CK, creatine kinase-MB fraction, and troponin I than those in control group (P < 0.05). No significant differences in bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was no statistically different of MACE between the two groups (P > 0.05). CONCLUSIONS: Intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions effectively improved myocardial perfusion and no increased bleeding in ST-segment elevation myocardial infarction patients.

Human hair derived uPA loaded capsules with dual near-infrared (I and II biowindows) laser responsive capabilities for multi-effective thrombolysis therapy.

Problems such as massive hemorrhage caused by uncontrolled drug dosage are the main significant obstacles in clinical thrombolytic therapy, which are prominently due to the lack of targeting and controlled release ability of efficient thrombolytic drug systems. In recent years, our team demonstrated that the photothermal effect can facilitate the thrombolytic effect of urokinase plasminogen activator (uPA). However, conventional photothermal agents are relatively expensive or contain heavy metals. If drug delivery systems with low toxicity, minimized heavy metal elements and easy accessibility (preferably provided by human self) can be developed, they will be of value in the future related applications. Herein, uPA-loaded human black hair derived nanoparticles with gelatin capsules (uPA@HBHNP@GNCs) were applied for the first time as a thrombolytic system. Upon irradiation by near-infrared I window (NIR-I) laser or II window (NIR-II) laser, the photothermal effect of HBHNP was triggered to promote the melting of the gelatin encapsulated around the outer layer, thereby realizing the targeted release of uPA. The in vitro and in vivo experiments demonstrated that the deep response to NIR (especially II window) of this system exhibited a satisfactory thrombolytic effect with ideal biosafety. Briefly, the proposed hair derived drug delivery system has the characteristics of human source, low cost, minimum heavy metal components, deep response to NIR (II window) laser, and good biocompatibility, which is expected to be expanded to the treatment for some diseases, even in deep tissue areas.

Thrombolytic treatment of prosthetic valve thrombosis: a study using Urokinase.

OBJECTIVE: We analysed the efficacy and safety of thrombolytic therapy with urokinase in patients with prosthetic valve thrombosis. METHODS: Twenty-three patients with valve thrombosis received thrombolytic treatment using urokinase. First, a 250,000 IU intravenous bolus injection was administered as a loading dose, followed by intravenous infusion of 100,000 IU/h for 10 h and anticoagulation with low molecular weight heparin every day. The maximum treatment time was 5 days, i.e., until the transvalvular pressure gradient was normal or close to normal. Transthoracic echocardiography (TTE) was used every 12 h to monitor whether the thrombus was reduced and whether there was haemodynamic improvement. Routine blood tests, the prothrombin time (PT), international normalized ratio (INR) and complications were observed every day. RESULTS: Sixteen (69.6%) patients were successfully treated with thrombolytic therapy: 2/2 (100%) aortic valves and 14/21 (66.7%) mitral valves. The partial success rate of this study was 13.0% (3/23). Four patients did not show any improvement in haemodynamics. Two cases had slight urine haemorrhage. One patient died of severe cerebral haemorrhage and shock. The overall mortality was 13.0% (3/23), including two patients who died after subsequent surgery. CONCLUSION: Urokinase is more convenient and successful in the treatment of PVT. More experience may make TT the optimal treatment for PVT, especially in high-risk surgical situations.

The safety and efficacy of pharmaco-mechanical thrombolysis in lower-extremity deep venous thrombosis.

OBJECTIVE: The aim of this study was to investigate the impact of accelerated pharmaco-mechanical thrombolysis (PMT) with low-dose second-generation urokinase for the management of cases with lower-extremity deep venous thrombosis (DVT), and to compare its efficacy in subjects with acute and subacute DVT. METHODS: Thirty-five patients with acute (< 15 days) or subacute (15-30 days) DVT who underwent PMT in a tertiary centre were enrolled in this single-arm, prospective study. Following the placement of a temporary vena cava filter, urokinase (200 000 IU) was administered into the occlusion through a multi-hole catheter for 15 to 20 minutes. Control venography was performed to assess venous flow and the rate of acute recanalisation. Percutaneous balloon dilatation and stent placement were carried out in case of a residual iliac vein stenosis of > 50%. Any residual thrombi were suctioned with an aspiration catheter. The primary outcome measures of this study were the percentages of vessel patency and PTS in the third month after PMT. RESULTS: Complete recanalisation was noted in 23 (66%) patients, while two (6%) had poor recanalisation. The rate of minor complications was 14%. None of the subjects experienced major complications, such as intracranial haemorrhage or pulmonary embolism. No mortality was recorded during the three months of follow up. Control duplex ultrasonography in the third month revealed that the target vein was patent in all subjects. None of the subjects experienced PTS during follow up. In addition, the percentage of acute complete recanalisation was significantly higher in subjects with acute DVT compared to those with subacute DVT (95 vs 27%, p < 0.001). CONCLUSION: PMT with an accelerated regimen of low-dose urokinase provided excellent efficacy in the resolution of thrombus and prevented the development of PTS in the midterm when used for the management of lower-extremity DVT.

Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study.

BACKGROUND: Prourokinase is a single-chain plasminogen activator presenting with fewer hemorrhagic complications and reduced reocclusion rate compared with the conventional fibrinolytic agents in patients with coronary artery disease. However, prourokinase intracoronary injection during PCI for treating patients with ST-segment elevation myocardial infarction (STEMI) is rarely investigated. Therefore, this study aimed to evaluate the efficacy and safety of intracoronary prourokinase during the percutaneous coronary intervention (PCI) in treating STEMI patients. METHODS: Fifty STEMI patients who underwent primary PCI were consecutively enrolled and randomly assigned to intracoronary prourokinase group (N = 25) or control group (N = 25). During the primary PCI procedure, patients in the intracoronary prourokinase group received 10 ml prourokinase injection, while patients in control group received 10 ml saline injection as control. The primary endpoints were coronary physiological indexes, the secondary endpoints were angiographic assessments, myocardial infarct size/reperfusion assessment, cardiac function evaluations, major adverse coronary events (MACEs) and hemorrhagic complications. All patients were followed up for 3 months. RESULTS: Post PCI, the index of microcirculatory resistance (IMR) was decreased in intracoronary prourokinase group than that in control group (34.56 ± 7.48 vs. 49.00 ± 8.98, P < 0.001), while no difference of coronary flow reserve (CFR) (2.01 ± 0.32 vs. 1.88 ± 0.23, P = 0.267) or fractional flow reserve (FFR) (0.89 ± 0.05 vs. 0.87 ± 0.04, P = 0.121) was found between the two groups. The thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) (P = 0.024), peak values of creatine kinase (CK) (P = 0.028), CK isoenzyme-MB (CK-MB) (P = 0.016), cardiac troponin I (cTnI) (P = 0.032) and complete ST-segment resolution (STR) (P = 0.005) were better in intracoronary prourokinase group compared with control group. At 3-months post PCI, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were higher, while left ventricular end-diastolic diameter (LVEDd) was lower in intracoronary prourokinase group compared with control group (all P < 0.05). There was no difference in hemorrhagic complication or total MACE between the two groups. CONCLUSION: Intracoronary prourokinase during PCI is more efficient and equally tolerant compared with PCI alone in treating STEMI patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016207 . Prospectively registered.

Sequential interventional therapy for Budd-Chiari syndrome associated with fresh inferior vena cava thrombosis.

OBJECTIVE: Our study aimed to evaluate the safety and efficacy of sequential interventional therapy for Budd-Chiari syndrome (BCS) caused by obstruction of the inferior vena cava (IVC) with fresh thrombus in the IVC. METHODS: Full medical records were obtained for 20 patients with BCS associated with fresh IVC thrombus who received sequential interventional therapy from 2014 to 2019 at our hospital. All patients underwent small-diameter percutaneous transluminal angioplasty (PTA) balloon catheter predilation combined with sequential catheter-directed thrombolysis and large-diameter PTA balloon dilation. Ultrasound examinations were performed at 1 week, 1 month, 3 months, and every 6 months thereafter. Therapeutic effects and perioperative and postoperative adverse effects were recorded to assess the safety of the treatment. RESULTS: All 20 patients were treated with small PTA balloon catheters (diameter, 10-14 mm) to predilate the occlusive segment of the IVC. Urokinase 400,000 to 600,000 (465,000 ± 93,000) units was administered to patients through the catheter for 6 to 20 (9.7 ± 4.2) consecutive days postoperatively. Ultrasound re-examination showed that the IVC thrombus disappeared completely in 14 patients (70.0%), and a small amount of the old thrombus remained in 6 patients (30.0%). After thrombolysis, all 20 patients received PTA balloon dilation (diameter, 26-30 mm) in the stenosed IVC segment, and blood flow recovered subsequently. No pulmonary embolism or death occurred in the perioperative course. The perioperative survival rate was 100.0%. CONCLUSIONS: Sequential interventional therapy for BCS associated with fresh IVC thrombus is safe and effective.

Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction.

OBJECTIVE: Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking. METHODS: In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated. RESULTS: No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK. CONCLUSION: Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.