Intra-arterial Fibrinolytic Therapy Research Articles

Influence of Intraoperative Intra-arterial Thrombolysis on Long-term Clinical Outcomes in Patients With Acute Popliteal Artery Aneurysm Thrombosis

Introduction: Acute lower limb ischemia (ALI) after popliteal artery aneurysm (PAA) thrombosis represents a challenging problem. In the last edition in 2017 from European Society for Cardiology specific recommendations for PAA treatment are lacking [1]. Generally for Rutherford grade II ischemia surgery is recommended. Intraoperative intra-arterial fibrinolytic therapy has been proposed as an adjunct to surgical procedure[ 2].The aim of this research was to investigate outcomes of intraoperative intra-arterial thrombolysis in the treatment of acute PAA thrombosis Rutherford grade IIa and IIb in terms of major adverse limb event (MALE), overall survival and intrahospital complications, especially those associated with bleeding. Methods: A total of 156 patients (Rutherford grade IIa and IIb) with acute PAA thrombosis were admitted between January 1st 2009 and January 1st 2015. We divided PAA patients in two groups, those who underwent (20 patients) and those who didn't undergo additional treatment with intraoperative intra-arterial thrombolysis (136 patients). By using covariables from baseline and angiographic characteristics, a propensity score was calculated for each patient. Each patient who underwent intraoperative thrombolysis was matched to 4 patients from non-thrombolysis group. Thus, comparable patient cohorts (20 in thrombolysis and 80 in non-thrombolysis group) were identified for further analysis. Primary end-point was MALE and secondary all-cause mortality. Results: Patients in thrombolysis group received less frequent fasciotomy (20% vs 56.25%, p=0.02), and had longer hospital stay (10.60 vs 7.04, p< 0.01). Same group had more common wound/hematoma related intervention (25% vs 8%, p=0.13) less common MALE events (0% vs 11.25%, p=0.19), but these differences weren't statistically significant. There were no cases of intrahospital death nor major hemorrhage in both groups. After median follow-up of 49 months, the estimated MALE rate was significantly lower in thrombolysis group (30% vs 65%) (χ 2 =11.50, DF=1, P< 0.01, log rank test). On the other hand, after same follow-up, patients in thrombolysis group had significantly lower mortality rate (20% vs 42.65%) (χ 2 =4.87, DF=1, P=0.03, log rank test). Conclusion: Vascunet and Swedish registry for popliteal artery aneurysm showed 30-day amputation rate of 6.5% and 3.3% respectively [3]. Mainly to address this critical issue arose the strategy of initial thrombolytic treatment for ALI associated with PAA thrombosis. Catheter directed intraaterial thrombolysis prior to surgery can achieve extremity revascularization and reestablish patency of small runoff vessels, providing more favorable conditions for open surgical or endovascular repair to follow in semi- urgent, or elective manner [4]. Systematic review published by Kropman et al. showed that the limb salvage rate was not different with preoperative thrombolysis when compared to the patients who did not undergo thrombolysis [5]. In this research we found that intraoperative intra-arterial thrombolysis in treatment of acute PAA thrombosis showed a significant reduction in terms of MALE events and even improves overall survival. No significant differences have been shown between groups in bleeding complications, except loco-regional. Disclosure: Nothing to disclose

A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

Background and purposeRecanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few...

O-006 Pharmaco-mechanical clot disruption using a balloon infusion wire in an acute rabbit common carotid artery thromboembolic occlusion model

PurposeRecanalization using intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective strategy for early reestablishment of cerebral blood flow in acute ischemic stroke. To validate...

Intra-Arterial Fibrinolysis for Acute Ischemic Stroke

See related article, pages 2633–2639. For nearly a decade, intra-arterial fibrinolytic therapy for acute ischemic stroke has stood poised on the threshold of a definitive evidential basis and widespread acceptance. The positive result of the phase 3 PROACT II trial in 1999 appeared to validate the pathophysiologically eminently reasonable strategy of endovascular recanalization in acute ischemic stroke.1 Endovascular therapy delivers lytic agent at high concentration directly to the clot, increasing lysis rates compared with intravenous therapy, while minimizing systemic exposure and extracerebral bleeding complications.2 Leading stroke centers adopted endovascular recanalization therapies as a common off-label treatment option for patients beyond the 3-hour window.3 However, proponents of evidence-based medicine noted that a single, small phase 3 clinical trial was insufficient to provide definitive proof of efficacy. The US Food and Drug Administration and international regulatory agencies did not approve a stroke label for pro-urokinase. The expense of a confirmatory phase 3 trial of pro-urokinase proved daunting to pharma and none was undertaken. In US national practice guidelines, intra-arterial fibrinolysis occupied a gray zone, receiving a Level B recommendation, indicating the incomplete foundation of a single dose-ranging and single positive phase 3 trial.4 The limitations of this evidential base have prevented regional emergency medical systems from organizing delivery of patients directly to endovascular hospitals. The results of the MELT trial, reported in this issue of Stroke , are therefore very welcome, providing additional information regarding intra-arterial fibrinolytic therapy that complements and supports previous studies. …

Does the Merci Retriever Work?

Section Editors: Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP Technically, it works. And remarkably so. The Merci Retriever is a mechanical embolectomy device designed to reopen occluded vessels by extracting occlusive thrombi from the cerebral vasculature. In the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial (parts I and II combined), among 151 patients enrolled in the intention-to-treat group; partial or complete recanalization by use of the device alone was achieved in 46%.1 This rate substantially exceeded that in the prespecified comparator group—patients enrolled in the control arm of the Prolyse in Acute Cerebral Thromboembolism (PROACT-II) trial (18%). The associated probability value of <0.0001 indicates a less than 1 in 10 000 chance that this result occurred by chance. The Merci Retriever indeed works. And it works well where we most need it to work: on proximal occlusions for which there was previously no good therapy. Proximal carotid terminus and M1 middle cerebral artery thrombi respond poorly to IV or intra-arterial fibrinolytic therapy, likely attributable in large part to the sheer volume of the clot burden requiring enzymatic digestion. The average volume of carotid terminus thrombi (0.4 ml) is more than an order of magnitude larger than that of M2 middle cerebral artery division thrombi …

Strategy for the Treatment of Acute Thromboembolic Stroke Involving an Internal Carotid Artery

With the recent improvement of endovascular techniques, intra-arterial local fibrinolytic therapy has become widely available for treatment of acute embolic stroke and there is some evidence that it could be superior to conventional approaches (1-6). However, because of high mortality and morbidity, strokes involving the internal carotid artery (ICA) and featuring acute thromboembolic occlusion remain problematic (7). We have successfully performed intra-arterial local fibrinolytic therapy via the anterior communicating artery through the contra-lateral ICA in two consecutive cases of thromboembolic occlusion of the ICA, anterior cerebral artery (ACA) and middle cerebral artery (MCA), and obtained satisfactory results.We here present details of this new technique applied for the two cases and discuss the efficacy of this method compared with conventional approaches.

Value of transesophageal echocardiography, esophago-gastroduodenoscopy and retinoscopy prior to intra-arterial fibrinolytic therapy in patients with peripheral arterial disease.

We prospectively investigated the need for esophagogastroduodenoscopy (EGD), transesophageal echocardiography (TEE) and retinoscopy for pre-interventional screening in patients with peripheral arterial occlusive disease (PAD) prior to intraarterial fibrinolytic therapy. 212 consecutive patients suffering from PAD (164 male and 48 female, mean age: 64 +/- 11 years, 161 patients stage II of Fontaine's classification, 10 patients at stage III and 41 patients at stage IV) referred for interventional treatment were included. 173 EGDs, 169 TEEs and 188 retinoscopies were performed within one week prior to fibrinolysis. 114 patients had all three examinations. Pathologic findings were detected in 56 (49%) of the 114 patients: 23 erosions, 12 ulcers, 2 esophagites, 1 gastric carcinomata, 3 intracardiac thrombi, 5 aortic thrombi, 11 diabetic and 5 hypertensive retinopathies and 1 with retinal aneurysms. 30 patients (25%) received fibrinolytic therapy, despite a contraindication: The one patient with ventricular thrombus was treated as an ultimate therapy, and amputation was prevented. Two patients showing plaques covered by large thrombi in the descending thoracic aorta were treated because cranial embolism should not occur. Four diabetic patients with multilevel disease, severe claudication and prior retinal bleeding were treated. Fibrinolytic therapy was started on 23 patients after complete healing of the mucosal lesions. TEE revealed potential sources of embolization in 4% of the patients and is justified to reduce the individual risk. Retinoscopy should be done in patients with diabetes mellitus and hypertension, and if prior bleeding is present fibrinolysis should be done only if other treatment-regimes are not available.

Evaluation of Local Intra-Arterial Fibrinolytic Therapy for Acute Middle Cerebral Artery Occlusion

Fibrinolytic therapy for acute ischaemic stroke has been investigated in several clinical trials, with various protocols. This retrospective study was undertaken to evaluate the efficacy and limitation of local intra-arterial fibrinolytic therapy using urokinase (UK) in patients with acute middle cerebral artery occlusion. Fifty patients were treated with local intra-arterial fibrinolytic therapy within six hours after onset of symptoms. The median National Institutes of Health Stroke Scale (NIHSS) score was 17 (range, 6 to 28).Two hundred and forty thousand IU of UK was administered through a microcatheter for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. Maximum dosage of UK was 0.96 x 106 IU. Recanalization efficacy was evaluated at the end of fibrinolytic therapy and intracranial haemorrhage was assessed within 24 hours. Clinical outcome was evaluated three months after ictus with modified Rankin scale (RS). Thirty-nine patients (78%) obtained recanalization. Twenty-nine of 39 (74%) showed clinical improvement just after treatment. On the other hand, only 18% patients (2/11) who did not recanalize demonstrated improvement. Twenty-five of 50 (50%) patients recovered to RS score 0 or 1, however, only 28% of patients (5/18) with proximal M1 occlusion obtained good outcome and 39% of them (7/18) died. The mean time interval from onset to treatment did not affect outcome. The overall incidence of haemorrhagic event (HE) within 24 hours was 36%, however, 78% of patients with proximal M1 occlusion showed HE. Only one patient with HE clinically deteriorated. In conclusion, local intra-arterial fibrinolytic therapy could be a safe and effective method for acute middle cerebral artery occlusion, however, indication of this therapy for patients with proximal M1 occlusion should be carefully decided.

急性期脳梗塞に対する局所線溶療法の有用性およびその限界

急性期脳梗塞に対する局所線溶療法の有用性およびその限界

Direct PTA for Acute Ischemic Stroke

We have performed direct PTA for 23 patients with acute ischemic stroke. Occlusion was identified at extracranial internal carotid artery (ICA) in 6 patients, at extracranial vertebral artery (VA) in I, at intracranial ICA in 3, at middle cerebral artery (MCA) in 12, and at basilar artery (BA) in 1. Stenosis was identified at extracranial VA in 1 patient. In 4 of 6 patients of extracranial ICA, 1 of 1 patient of extracranial VA, 1 of 3 patients of intracranial ICA, 7 of 12 patients of MCA and 1 of 1 patient of BA, recanalization was observed. Fourteen of 22 occluded arteries (64%) were recanalized. The recanalization rate approximated that of local intraarterial fibrinolytic therapy. We have not experienced complications with this procedure. Direct PTA is promising and might be a novel recanalization technique.

Terapia fibrinolitica intra-arteriosa in occlusione vertebrobasilare acuta

Intra-arterial fibrinolytic therapy in acute vertebrobasilar occlusion is effective in saving the patient's life in 75% of cases if performed within 6 hours after the beginning of an ischemic event, without CT evidence of hypodense focal areas in the brain stem, cerebellum or thalamic nucleus. The initial clinical aspect of vertebrobasilar stroke is more often evolving. Only in 1/3 of cases is coma present at the beginning. In vertebro-basilar occlusion prognosis is determined by clinical and neuroradiological aspects. The outcome depends mainly upon how much brain stem function is lost during the reperfusion time, and the kind of vertebrobasilar occlusion. The case we present concerns a 38 year old man with acute onset of cerebral stroke without initial clinical signs of vertebrobasilar localization due to a basilar artery occlusion distal to AICA. Urokinase infusion was performed within three hours from the clinical onset up to a total amount of 1.400.000 UI. Reperfusion was observed one hour after the beginning of the intravascular therapy. The clinical course was favorable with good recovery (moderate superior right paresis, controlateral light cerebellar syndrome).

Intraoperative Fibrinolytic Therapy for Salvage of Limbs With Acute Arterial Ischemia: An Adjunct to Thromboembolectomy

The purpose of this prospective study was to determine the value of intraoperative intra-arterial fibrinolytic therapy (IIFT) in patients with acute arterial ischemia as an adjunct to mechanical thromboembolectomy. Sixty-six femoropopliteal or distal acute arterial occlusions were assessed by means of arteriography and Doppler imaging pre- and postoperatively. Two groups of patients were compared: one (n = 35) in which mechanical thromboembolectomy was applied as the single technique and another (n = 31) in which 250,000 IU of urokinase diluted in 250 ml of normal saline solution was instilled at the end of mechanical thromboembolectomy over a 30-minute period with the arterial inflow occluded. Candidates for IIFT were selected according to a nonrandomized method. Intraoperative arteriography showed residual thrombus in 20 (30.3%) patients and unsuspected arterial lesions in 23 (34.8%). Thrombosis recurrence was associated with residual thrombus (p < 0.001) and amputation (p < 0.001). The ankle/brachial index increased significantly (p < 0.05) in the patients who received IIFT (0.88 +/- 0.03) in comparison with those who underwent mechanical thromboembolectomy (0.75 +/- 0.05). Although the percentages of distal revascularization and amputation did not differ significantly between the two groups, quantitatively the results were better in the IIFT group (80.65% success and 9.68% failure) compared to the mechanical thromboembolectomy group (60% success and 22.86% failure). There was no bleeding due to IIFT. Significant variables in our study were diabetes (p < 0.05), the time period of 12 to 24 hours before the surgery (p < 0.05), and the severity of the ischemia in association with rest pain (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinolytic therapy for acute embolic stroke: intravenous, intracarotid, and intra-arterial local approaches.

To clarify the efficacy and limitations of the intra-arterial local infusion of a high-dose fibrinolytic agent for acute embolic stroke, we analyzed the results of 44 patients and compared them with those of 51 patients treated with intracarotid (18 patients) or intravenous (33 patients) infusion therapy. Ten megaunits of recombinant tissue plasminogen activator or 24 x 10(4) IU of urokinase were administered through a microcatheter placed into or proximal to an embolus for 20 minutes. When arterial recanalization was not achieved, a second or third infusion was performed. The rates of complete and partial recanalization just after the local infusion were 52 and 32%, respectively. They were high in middle cerebral and basilar artery occlusion and low in internal carotid artery occlusion (69, 78, and 20%, respectively). In our use, there was no difference between tissue plasminogen activator and urokinase in restoring blood flow. The mean time interval from onset to recanalization in patients with middle cerebral artery occlusion showing marked improvement was 4.8 hours, and it was 5.8 hours with basilar artery occlusion. The size of infarction was reduced, and the outcome was good in patients with complete recanalization achieved. The incidence of hemorrhagic infarction within 24 hours was 22%, and only one patient clinically deteriorated. In the intracarotid infusion group (20 x 10(4) IU of urokinase for 30 min), only two patients showed partial recanalization without clinical improvement. The incidence of hemorrhagic infarction was 28%. The outcome in this group and the intravenous infusion group (18 x 10(4) IU of urokinase a day for 1 wk) was poor compared with that in the local infusion group showing complete recanalization. This preliminary study appears to suggest that intra-arterial local fibrinolytic therapy could be a new strategy for acute embolic stroke.

Local intraarterial fibrinolysis in acute vertebrobasilar occlusion. Technical developments and recent results.

Local intraarterial fibrinolytic therapy (LIF) in patients with acute vertebrobasilar occlusion (AVBO) is a rational and if successful a life saving treatment. The recent progress in this field is determined by the use of microcatheters for superselective basilar artery catheterisation and a "short time, highdose" regimen using 750.000 IU Urokinase in not more than two h. Two out of 7 patients died and 1 did not improve to a better than a locked-in-state. Four patients however survived with excellent outcome.

Fibrinolytic treatment of residual thrombus after catheter embolectomy for severe lower limb ischemia

Intraoperative intraarterial fibrinolytic therapy (IIFT) was employed in 28 patients with acute limb ischemia. In 17 patients, significant residual calf thrombus was demonstrated by completion arteriography after standard balloon catheter thromboembolectomy, whereas in 11, pretreatment arteriography was not obtained. With the patient systemically heparinized, a bolus of fibrinolytic agent was instilled into the distal vessels below an inflow occlusion clamp. Among the 17 patients under angiographic control, arteriography was repeated after 30 minutes and a second bolus was injected if significant residual thrombus was still present. Successful lysis was achieved in 88% of these 17 limbs and streptokinase (SK) and urokinase (UK) were equally effective. The dosage of SK varied between 50,000 and 150,000 units (seven patients) and of UK between 35,000 and 150,000 units (21 patients). Serum fibrinogen levels declined significantly after IIFT (t test; p < 0.05), but the average level remained within the normal range. Major bleeding developed in two patients, both of whom received SK and underwent a concomitant major abdominal vascular procedure, with a severe fall in fibrinogen values to 10 and 17 mg/dl. A minor groin hematoma occurred in one patient treated with UK. There was a significant difference in the incidence of bleeding between SK (27) and UK (121) (X2; p < 0.05). Compartment syndrome developed in six limbs (21%). Amputation was required in two patients (7%). There was no correlation between prolongation of ischemia time as a result of IIFT and the incidence of compartment syndrome. IIFT is effective therapy for residual thrombi not retrievable by balloon catheter techniques and is safe provided the serum fibrinogen level is maintained greater than 100 mg/dl. UK in the dose range of 100,000 to 150,000 units per bolus injection is currently the preferred agent.

Fibrinolytic treatment of residual thrombus after catheter embolectomy for severe lower limb ischemia.

Intraoperative intraarterial fibrinolytic therapy (IIFT) was employed in 28 patients with acute limb ischemia. In 17 patients, significant residual calf thrombus was demonstrated by completion arteriography after standard balloon catheter thromboembolectomy, whereas in 11, pretreatment arteriography was not obtained. With the patient systemically heparinized, a bolus of fibrinolytic agent was instilled into the distal vessels below an inflow occlusion clamp. Among the 17 patients under angiographic control, arteriography was repeated after 30 minutes and a second bolus was injected if significant residual thrombus was still present. Successful lysis was achieved in 88% of these 17 limbs and streptokinase (SK) and urokinase (UK) were equally effective. The dosage of SK varied between 50,000 and 150,000 units (seven patients) and of UK between 35,000 and 150,000 units (21 patients). Serum fibrinogen levels declined significantly after IIFT (t test; p less than 0.05), but the average level remained within the normal range. Major bleeding developed in two patients, both of whom received SK and underwent a concomitant major abdominal vascular procedure, with a severe fall in fibrinogen values to 10 and 17 mg/dl. A minor groin hematoma occurred in one patient treated with UK. There was a significant difference in the incidence of bleeding between SK (2/7) and UK (1/21) (chi 2; p less than 0.05). Compartment syndrome developed in six limbs (21%). Amputation was required in two patients (7%). There was no correlation between prolongation of ischemia time as a result of IIFT and the incidence of compartment syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study.

The possibility that intra-arterial local infusion of fibrinolytic agents may achieve recanalization of previously occluded carotid territory arteries in acute stroke was tested in a prospective angiography-based open pilot study at two centers. Fifteen of 20 patients with acute symptoms (mean treatment-onset interval 7.6 hours) demonstrated complete recanalization; 10 of the 15 patients exhibited clinical improvement of varying degree by the time of hospital discharge. Four of the 20 patients suffered hemorrhagic transformation of the infarcted territory without clinical deterioration or demise. Because of the study format and the limited number of patients, dose responses for recanalization and risk relations were not established. We conclude that local intra-arterial fibrinolytic therapy may lead to cerebral arterial recanalization in acute carotid territory thrombotic stroke. The particular implications and limitations of this approach are discussed.

Vascular recanalizing techniques in the hind brain circulation.

Percutaneous transluminal angioplasty (PTA) was performed in 45 patients with a manifest subclavian steal syndrome. Thirty-five of those patients were subjected to follow up examinations over a period of 6 to 18 months. Five patients suffered from severe restenosis and were treated again. Two thirds of the patients benefited from the treatment. PTA of the proximal vertebral artery was performed in 15 patients with bilateral occlusive lesions of the extracranial vertebral arteries. In 13 of these cases the neurological and the vascular states of the patients were regularly reexamined, 8 showed a marked improvement. During the 2 to 25 month observation period (average 15 months post-PTA) reocclusion was observed in only two cases. These showed no recurrent neurological sequelae. Forty-three consecutive patients with acute vertebro-basilar or basilar occlusion received intraarterial fibrinolytic therapy with streptokinase or urokinase. Twenty-three of these had presented severe deficits at the beginning of therapy (e.g. complete tetraplegia, comatous state for more than 6 hours). None of this group survived. By contrast the 20 other patients in this group presented with incomplete fluctuating or progressive motor deficits. None was comatous for more than 6 hours. Fourteen patients (33% in this group) survived. Local intraarterial fibrinolytic therapy is the only therapy successful in the treatment of progressive stroke from vertebro-basilar thrombosis.

Intraarterial fibrinolytic therapy for popliteal and tibial artery obstruction: comparison of streptokinase and urokinase

Experience with using intraarterial fibrinolysis in the treatment of occlusive disease of the popliteal artery and runoff vessels is limited. We describe the techniques and results in 25 patients with 30 fibrinolytic infusions of the popliteal and tibial arteries and compare them with the initial and long-term results of treatment using streptokinase and urokinase. The roles of catheter delivery systems and systemic heparin in the prevention of pericatheter thrombus were also studied. Urokinase was initially successful in 18 (90%) of 20 intraarterial infusions, whereas streptokinase was effective in 8 (80%) of 10 intraarterial infusions. Urokinase had the advantages of a shorter effective infusion time and fewer complications. Long-term follow-up was available in 20 of the successfully treated patients. Sixteen of these patients were doing well with an average follow-up of 27 months. The duration of the initial occlusion may be useful in identifying patients at risk for early reocclusion. No limbs were lost because of complications of therapy. The coaxial catheter system with a divided fibrinolytic dose provided protection against pericatheter thrombus, while systemic heparin was ineffective. Our results suggest that urokinase is more effective than streptokinase for intraarterial infusion in the treatment of occlusion of the popliteal and tibial arteries; this procedure is an important alternative to surgery or an adjuvant to surgery in selected patients.

Intraarterial fibrinolysis: long-term results.

Intraarterial fibrinolytic therapy was performed in 136 patients suffering from arteriosclerotic thrombosis of the iliac and femoropopliteal arteries. The initial success rate was 78%. Despite anticoagulation therapy, early recurrent thrombosis was observed in 10% of the patients. The 2-year cumulative patency rate after recanalization was 81%. These results are competitive with those of reconstructive vascular surgery. Therefore, intraarterial fibrinolysis has become a viable alternative to surgery in treating segmental peripheral occlusions more than 4 cm in length that are less than 6-9 months in duration.