Current indications and results of thrombolysis by intravenous recombinant tissue plasminogen activator

A number of landmark trials have proven the efficacy of thrombolysis by intravenous recombinant tissue plasminogen activator in the acute phase of the ischemic stroke. Despite the recently extended time window of 4.5 hours, the number of people who are being treated in most centers is low. Several reasons seem to account for this, including poor recognition of symptoms, delays in emergency transport, low levels of public awareness, or age limits originally imposed by drug regulatory rules. Trials are ongoing to possibly extend the indications to the treatment. A major effort is to extend the time window by bridging the treatment with neuroprotective approaches, or by identifying subgroups that may particularly benefit from recanalization and reperfusion. Procedures using ultrasounds or alternative intravenous compounds are also being investigated with promising results.     

Rapid thrombectomy of superior sagittal sinus and transverse sinus thrombosis with a rheolytic catheter device

Thrombosis of the dural venous sinuses is a potentially lethal condition that remains a diagnostic dilemma. Clinical outcome is typically dependent on the timeliness of diagnosis and definitive treatment. We report a case of successful rapid thrombectomy of extensive thrombus within the superior sagittal and transverse sinuses using a rheolytic catheter device. This appears to be a promising treatment option, particularly in those patients who do not respond to other, more established, forms of therapy.     

Complete recovery after early intraarterial recombinant tissue plasminogen activator thrombolysis of carotid T occlusion

Carotid T occlusion (intracranial carotid bifurcation occlusion with involvement of A1 and M1 segments) is associated with poor outcome. In most cases, treatment with intraarterial thrombolysis within a 6-hour window has been unsuccessful. We describe the case of a 26-year-old woman who presented with severe neurologic deficits (National Institutes of Health Stroke Scale score of 23) secondary to angiographically proved right carotid T occlusion. She was treated with intraarterial infusion of recombinant tissue plasminogen activator that was started less than 3 hours after symptom onset (26 mg administered during 2 hours 15 minutes). Thrombolysis resulted in recanalization of all major intracranial vessels and complete neurologic recovery. Early intraarterial thrombolysis may be effective in the treatment of patients with carotid T occlusion and should be considered for appropriate candidates.     

Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries.

The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.     

Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis catheter

PURPOSE: To evaluate the performance of the Trellis-8 isolated thrombolysis catheter during single-session pharmacomechanical thrombectomy (PMT) combined with low-dose thrombolysis with tissue plasminogen activator (TPA) in the treatment of patients with acute deep vein thrombosis (DVT) and multiple comorbidities. MATERIALS AND METHODS: Retrospective analysis was performed of 19 consecutive patients with acute above-knee DVT treated by PMT with the Trellis device followed by venous angioplasty and stent placement. Isolated thrombolysis with low-dose TPA was used with all patients. Concurrent therapies included retrievable inferior vena cava filter insertion (n = 4). The primary endpoint was restoration of rapid inline venous flow; the secondary endpoint was thrombus clearance. RESULTS: Restoration of rapid inline venous flow was achieved in all cases; thrombus removal was less than 50% in one case (4%), 50%-95% in 18 cases (82%), and at least 95% in three cases (14%). The median administered dose of TPA was 13.4 mg per patient. The mean treatment time was 91 minutes per limb (range, 61-129 min), with a mean of 21 minutes per thrombosed segment (range, 8-31 min). There were no major complications. Primary patency rate of the treated venous segments at 2 days was 86% (n = 19) and the primary assisted patency rate was 100% at 30 days. Two patients died of advanced malignancy at 17 and 24 days. CONCLUSIONS: The Trellis system was an effective method for the treatment of acute DVT. Based on the present data, the Trellis system could prove to be a safe and feasible single-session PMT method for the treatment of acute DVT in a broader patient population and warrants further investigation in a large-scale study.     

Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis

PURPOSE: Catheter-directed thrombolytic dissolution of peripheral arterial and venous thrombus is in widespread use, yet the frequency and nature of associated complications remain ill defined. In an effort to better characterize the complications associated with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA), the clinical course of patients treated for lower extremity vascular occlusions at a single institution was reviewed. MATERIALS AND METHODS: Over a 9-year period, 653 consecutive patients were treated for lower extremity arterial (527 patients) or venous (126 patients) occlusions with catheter-directed UK (483 patients), rt-PA (144 patients), or both (26 patients). Decisions regarding the choice of thrombolytic agent were made by the clinician. In-hospital complications were subcategorized into hemorrhagic and nonhemorrhagic events and the rate of intracranial hemorrhage was specifically tabulated. RESULTS: There were no significant differences in the demographics or clinical presentation of patients treated with either UK or rt-PA. Bleeding complications occurred less often in the patients treated with UK (insertion site hematoma 21.9% vs. 43.8%, P<.0001, any bleeding necessitating transfusion 12.4% vs. 22.2%, P = .004, and intracranial hemorrhage 0.6% vs. 2.8%, P = .031). Cardiopulmonary complications necessitating transfer to the intensive care unit occurred more frequently in the patients treated with rt-PA (4.9% vs. 1.5%, P = .015). The risk of mortality was not statistically different between the UK and rt-PA treated patients (2.7% vs. 6.2%, P = .221). CONCLUSIONS: Thrombolysis appears safer with UK than with rt-PA, with a lower incidence of hemorrhagic complications. It is possible that this finding is related to differential dosing regimens or intrinsic pharmacologic differences between the agents. The observations of this retrospective analysis require confirmation with a prospective, randomized evaluation.     

Comparison of urokinase and tissue plasminogen activator for thrombolysis in rats

Microvascular thrombosis in free flap and replantation surgery may be amenable to thrombolytic therapy. A blinded, controlled, preliminary study in rats compared urokinase (UK) and tissue plasminogen activator (t-PA) on thrombolytic efficacy, systemic fibrinolytic effect, and reocclusion. Bilateral femoral vein clots were induced in 38 rats. Local infusion of UK, t-PA, or saline was performed. Fibrinogen levels were drawn from one group. A second group was evaluated for reocclusion up to one month. Ipsilateral lysis occurred for reocclusion up to one month. Ipsilateral lysis occurred in 10/12, 13/13, and 0/13 of the UK, t-PA, and saline groups, respectively, with no significant difference detected between the UK and t-PA groups. Contralateral clot lysis occurred in both the UK and t-PA groups. No significant differences in the fibrinogen levels was detected among the three groups. Reocclusion occurred only in the UK group.     

Localization of human malignant tumors with radioiodinated recombinant tissue plasminogen activator

Human recombinant tissue plasminogen activator (tPA), labeled with 131I(1.1 to 6.2 mCi) by the iodogen method, was administered intravenously to 15 patients with various soft-tissue malignant tumors after blocking of thyroidal radioiodine uptake. Gamma camera imaging was performed 4 and 24 hr after injection; three patients were also imaged 5 days following injection. We observed accumulation of radioactivity in primary and secondary lesions in 11 patients. In this preliminary study we did not detect any definite association between the magnitude of uptake and type of tumor. Tumors were usually visualized already after 4 hr but the uptake was more intense at 24 hr. The target-to-nontarget ratios at 24 hr, determined by computer analysis of stored images, varied from less than 1.2 to 2.1. This is the first demonstration of accumulation of radiolabeled tPA in malignant tissue. We do not know the mechanism of the uptake but because tPA is known to be avidly bound to fibrin, a component of the stroma of many malignant tumors, it is possible that [131I]tPA is bound to fibrin rather than taken up by the malignant cell; various possible cell uptake mechanisms are discussed. Due to the relatively early maximal uptake of this radiopharmaceutical it will be possible to substitute 123I for 131I, a possibility suggesting a potential clinical use of radioiodinated tPA for the detection of malignant tumors of various origin.     

Original report. Pulse-spray thrombolysis of thrombosed hemodialysis grafts with tissue plasminogen activator

OBJECTIVE: The purpose of this study was to evaluate pulse-spray pharmacomechanical thrombolysis with the use of tissue plasminogen activator in the recanalization of thrombosed hemodialysis access grafts. CONCLUSION: Pulse-spray pharmacomechanical thrombolysis with tissue plasminogen activator is an effective method for percutaneous recanalization of thrombosed hemodialysis access grafts with results similar to other percutaneous techniques.     

Rapid localization of indium-111-labeled inhibited recombinant tissue plasminogen activator in a rabbit thrombosis model

The thrombus localizing properties of indium-111-recombinant tissue plasminogen activator (111In-rt-PA) have been investigated in an effort to achieve prompt and accurate detection of thrombi. Unlike previous studies with rt-PA, the active plasminogen catalytic site was permanently inhibited with peptides of chloromethyl ketone so that the radiotracer binds to fibrin without causing fibrinolysis. Thrombi were created in the external jugular vein of 14 male New Zealand white rabbits followed by injection of 111In-rt-PA. The agent cleared rapidly in vivo with a half-time of 4.6 min. The thrombus: blood ratio in nonheparinized rabbits (n = 7) was 6.39 +/- 0.86. The ratio in heparinized rabbits (n = 4) was 3.11 +/- 0.23. Thrombi were clearly visible in the planar images of both groups 1 hr postinjection. The combination of rapid thrombus localization and positive images, especially in the presence of anticoagulation, suggests that further work is warranted with rt-PA thrombus imaging.     

Percutaneous catheter and guidewire fragmentation with local administration of recombinant tissue plasminogen activator as a treatment for massive pulmonary embolism

The purpose of this article is to report four patients with massive pulmonary embolism treated with percutaneous catheter and guidewire fragmentation and local administration of recombinant tissue plasminogen activator (r-TPA). Four patients with massive pulmonary embolism initially underwent pulmonary angiography. Thrombus fragmentation was performed with both standard angiographic guidewires and catheters followed by local infusion of 41–200 mg of r-TPA. Pulmonary angiography was repeated after treatment. All patients survived with improvement in their clinical status and eventual discharge from hospital. Angiography in all patients post treatment demonstrated improvement in pulmonary perfusion (mean Miller score before treatment 22.5; mean Miller score after treatment 5.75). No patient had a significant complication. Mechanical fragmentation of the thrombus followed by local infusion of r-TPA was an effective treatment for massive pulmonary embolism in these four patients with no significant complications. Received: 9 February 1998; Revision received: 7 July 1998; Accepted: 7 September 1998     

慢性下肢深静脉血栓应用球囊挤压联合置管溶栓效果观察

目的：探讨球囊挤压联合置管溶栓治疗慢性下肢深静脉血栓（LEDVT）的安全性和临床效果。方法：选择既往健康的外伤后慢性LEDVT成年患者29例,植入下腔静脉滤器,用小于目标血管（腘静脉）直径2 mm的球囊扩张挤压碎裂血栓,然后在球囊扩张状态下拖移使血栓移位,随后留置导管溶栓3～7 d,拔出导管后继续顺行溶栓3 d,1个月内取出滤器,随访观察疗效和并发症。结果：29例均成功完成,球囊扩张后血管全部即时再通;溶栓3～10 d后下肢肿痛缓解或消失,超声复查腘静脉以上深静脉均再通、局部狭窄显著改善,无严重并发症;随访平均（4.9±2.7）年,临床效果好,其中病程≤3个月者效果最好。结论：既往健康的外伤后慢性LEDVT患者应用球囊挤压联合置管溶栓治疗安全有效,以病程≤3个月者为佳。     

Fogarty球囊导管取栓联合双侧髂动脉球囊阻断术治疗急性肾动脉血栓1例

1 临床资料 患者,男,75岁,因"突发右侧腰痛16 h"入院.16 h前患者无诱因下突发出现右侧腰痛,呈持续性钝痛,伴血压升高,最高血压:200/180 mmHg(1 mmHg=0.133 kPa).既往史:伴有高血压病史、房颤病史5年余.急诊主动脉CTA提示:右肾动脉未见显影,考虑闭塞(图1①).结合患者有房颤病史...     

Combined direct percutaneous transluminal angioplasty and low-dose native tissue plasminogen activator therapy for acute embolic middle cerebral artery trunk occlusion

BACKGROUND AND PURPOSE: In embolic middle cerebral artery (MCA) trunk occlusion, recanalization with direct percutaneous transluminal angioplasty (PTA) may be preferable to time-consuming thrombolysis. However, distal embolization with small crushed fragments is a complication of direct PTA. We prospectively evaluated combined direct PTA and low-dose native tissue plasminogen activator (t-PA) therapy for acute embolic MCA trunk occlusion. METHODS: Fifteen patients underwent direct PTA. The embolus was successfully crushed in 12, who received subsequent native t-PA infusion. Direct PTA was performed with a balloon catheter, which was advanced into the occlusion site and inflated several times until recanalization was established. After PTA, 7.2 mg of native t-PA in 100 mL of isotonic sodium chloride solution was infused for 30 minutes. Neurologic status was evaluated at admission and immediately and 1 month after treatment. In all patients, follow-up CT was performed within 24 hours and 3-7 days after onset, and follow-up MR imaging, 1 month after onset. RESULTS: Direct PTA failed to crush the embolus in three of 15 patients; these three had no clinical improvement. In 11 of 12 patients, combined therapy was successful, with no technical complication. Although no symptomatic intracerebral hemorrhage occurred, one patient had a small hematoma. All patients with successful recanalization had marked clinical improvement. Although angiograms showed distal embolizations in 10, cortical infarctions were confirmed in only three at follow-up. CONCLUSION: Combined direct PTA and IV low-dose native t-PA therapy may be a safe alternative to thrombolytic therapy in some patients with embolic MCA trunk occlusion.     

Treatment of acute ischemic brain infarction with the assistance of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator

Background: Cerebral infarction is usually due to arterial occlusion. Prompt treatment with thrombolytic drugs can restore blood flow and improve recovery from an infarct.

Purpose: To evaluate the clinical efficacy and safety of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator (rtPA) in patients with acute middle cerebral artery (MCA) infarctions within 6 hours of the onset of symptoms.

Material and Methods: Sixteen patients (10 females and six males) aged from 42 to 61 years, with acute MCA territory infarcts were selected for treatment with local i.a. rtPA up to 6 hours after the onset of symptoms. Patient selection was based on clinical examination, computed tomography (CT), and digital subtraction angiography (DSA). A clinical evaluation was performed before treatment, at the time of discharge, and 90 days post-procedure on the basis of modified Rankin and NIHSS scores. Controls (n = 16, nine females and seven males) aged from 51 to 70 years were treated only with intravenous anticoagulation using i.v. heparin infusion. The control group was evaluated with multidetector CT (MDCT) angiography performed on entry to the study and at 2-4 hours afterwards.

Results: Eight patients (50%) achieved a modified Rankin score of 2 or less as the primary outcome after 90 days follow-up. The secondary clinical outcome at 90-day follow-up was as follows: NIHSS score ≤1, three (19%) of the patients; NIHSS score ≥50% decrease, nine (56%) of the patients. A recanalization rate of 75% was achieved in 12 of the 16 treated patients, but only 12.5% in two of the 16 patients in the control group. Intracerebral hemorrhage occurred in two (12.5%) of the patients in the treatment group, but in only one patient (6%) in the control group. There were no deaths in the treated group after thrombolysis up to the time of discharge; however, during the 90-day follow-up, two patients died compared to three patients in the control group (19% vs. 12.5% mortality rate).

Conclusion: Patients with cerebral infarction who were treated within 6 hours of onset using intraarterial rtPA thrombolysis had a significantly improved clinical outcome 90 days after the procedure compared to patients treated only with intravenous anticoagulation.     

Augmented experimental pulse-spray thrombolysis with tissue plasminogen activator, enabling dose reduction by one or more orders of magnitude

PURPOSE: To critically evaluate and optimize methodologic details of pulse-spray thrombolysis with tissue plasminogen activator (tPA) in a subacute rabbit inferior vena cava thrombosis model. MATERIALS AND METHODS: Occlusive inferior vena cava thrombi were produced in 104 rabbits and 2 days later were treated for 1 hour with pulse-spray thrombolysis using tPA. Methodologic variables included pulse frequency, concentration and amount of tPA, infusion versus pulse therapy, and admixture of heparin. After the rabbits were killed, residual thrombus was weighed. RESULTS: The authors' earlier standard regimen (3 mg of tPA in 6 mL of heparinized saline, 0.2-mL hand pulses, frequency 1 pulse per 2 minutes) produced 60% mean lysis. Optimization involved increasing the pulse frequency to two per minute and decreasing tPA concentration by 98% to 0.01 mg/mL, modifications that produced 22% more thrombolysis, despite 92% reduction in amount of tPA to 0.25 mg. CONCLUSION: Consistent with the in vitro work of other investigators, a roughly bell-shaped dose-response curve was elicited in vivo for pulse-spray with tPA. By diluting tPA to an optimal level, and increasing pulse frequency to two per minute, thrombolysis was markedly augmented. These results suggest that the conventional dose of tPA used for clinical pulse-spray thrombolysis can be reduced by one to two orders of magnitude, possibly markedly reducing procedural risk.     

AngioJet机械性血栓抽吸联合导管接触溶栓治疗急性下肢深静脉血栓形成效果观察

目的 探讨经皮机械性血栓清除术(PMT)联合导管接触溶栓(CDT)治疗下肢深静脉血栓形成(DVT)的安全性和近期效果.方法 回顾性分析2017年1月至2018年12月徐州医科大学附属医院收治的56例急性中央型、混合型下肢DVT患者临床资料.其中28例接受AngioJet机械性血栓抽吸联合CDT治疗(A组),28例接受单...