Acosta and Kuoppala (2015) presented results after intra-arterial thrombolysis with low dose rtPA from 2001 to 2012 in two large vascular centers in Sweden. Technical success rate for thrombolysis of occluded endoprostheses, bypasses and native artery occlusion was 91%, 89% and 73%, respectively. Amputation-free survival rate at 1 year was 73%. Major hemorrhage occurred in 104 procedures (13.9%); 43 (5.7%) were so severe that thrombolysis was discontinued in advance. All three (0.4%) hemorrhagic strokes were fatal.

Grip et al. (2014) reported 749 intra-arterial thrombolyses in 644 patients with ALI. The purpose of this study was to evaluate different thrombolytic treatment strategies. Median patient age was 73 years, 47.1% of the procedures were done in women. The aetiology of ischaemia was graft occlusion in 38.8%, acute arterial thrombosis in 32.2%, embolus in 22.3% and popliteal aneurysm in 6%. Concomitant heparin infusion was used in 63.2%. The mean dose of rt-PA administered was 21.0 mg, with a mean duration of 25.2 h. Technical success was achieved in 80.2%. Major amputation and death within 30 days occurred in 13.1% and 4.4% respectively. Bleeding complications occurred in 30.3% of treatments. Three patients (0.4%) suffered from fatal intracranial bleeding. Amputation-free survival at 30 days was 83.6%. Comparing the results of two different centres, the authors concluded that continuous heparin infusion during intra-arterial thrombolysis offers no advantage. Acosta and Kuoppala (2015) had come to the same conclusion.

Kashyap et al. (2011) assessed outcomes in 119 patients (129 limbs) treated for ALI with intra-arterial thrombolysis. Percutaneous mechanical thrombectomy was utilized in nearly half the cases (47%) in addition to thrombolysis. The mean follow-up was 16.8 months. Technical success was achieved in 82% cases. The 30-day mortality rate was 6.0% with all 30-day deaths occurring in females. One (0.76%) central nervous system haemorrhage was noted in this cohort. Eighty-two percent of patients were alive and had their limb intact at 30 days after endovascular treatment for ALI. Primary patency for the entire cohort at 12 and 24 months was 50.1% and 37.7%, respectively, while secondary patency was 74.0% and 65.3%. Survival of the entire cohort at 12 months was 85.7%. Thrombolysis >3 days was associated with an increased risk of limb loss and should be therefore limited to < 3 days.

123 patients undergoing thrombolysis for acute graft occlusion in the lower limb were retrospectively reviewed by Koraen et al. (2011). 67% had synthetic grafts. ALI (74%) was the dominating symptom preceding thrombolytic treatment. In 29% of cases, no adjunctive interventions were required, whereas 21% underwent open surgery, 39% endovascular intervention, and 11% underwent a hybrid procedure. Technical failure of thrombolysis occurred in 18 patients (15%). Fatal myocardial infarction occurred in three patients (2.4%). There were two patients with hemorrrhagic stroke (1.6%), of which one was fatal. Major hemorrhage occurred in 13.2% of the patients. The mortality rate was 6.5% and 13% at 1 and 12 months, respectively. The amputation-free survival rate was 89% and 75% at 1 and 12 months, respectively. One advantage with successful thrombolysis over the open surgical technique was in this study that thrombolysis allowed an accurate assessment of the vascular tree and underlying causes contributing to bypass graft failure. In this study the majority of patients underwent subsequent correction of an underlying stenosis within the graft and/or of an in- or outflow stenosis. In addition, thrombolysis had been assumed to result in more patent outflow vessels compared with surgical thrombectomy.

Schrijver et al. (2016) retrospectively analyzed 159 consecutive patients with 89 native artery (56%), and 70 prosthetic bypass graft (44%) occlusions of the lower extremity. Complete (>95%) lysis was achieved in 69% of native arteries and bypass grafts. Major hemorrhagic complications occurred in 12% (4% hemorrhagic strokes, of which 2% were fatal) of native arteries and in 7% (0% hemorrhagic stroke) of bypass grafts. The 30-day mortality rate was 6% in native arteries and 1% in bypass grafts, and the 30-day amputation rate was 10% in native arteries and 13% in bypass grafts. Amputation-free survival at 1 year was 76% for native arteries and 78% for bypass grafts and at 5 years was 65% for native arteries and 51% for bypass grafts. Long-term outcome after catheter-directed thrombolysis for acute lower extremity occlusions of native arteries compared with prosthetic bypass grafts was not different in this study.

Schernthaner et al. (2014) retrospectively compared the safety and efficacy of ultrasound-accelerated thrombolysis (UAT) and standard catheter-directed thrombolysis (CDT) in patients with acute and subacute limb ischemia. UAT was performed in 75 patients, and CDT was performed in 27 patients. Complete lysis was achieved in 72.0% (UAT) and 63.0% (CDT) of patients, respectively; hemodynamic success was achieved in 91.8% (UAT) and 92.3% (CDT). Major and minor bleeding combined was lower in UAT (6.7%) versus 22.2% in CDT. Median long-term survival was not significantly different between UAT and CDT. According to this data the observed lower risk of total bleeding might be an advantage of UAT. In the Dutch randomized trial comparing standard CDT and UAT for the treatment of arterial thromboembolic occlusions (DUET study), thrombolysis was significantly faster in the UAT group (17.7 ± 2.0 h) than in the CDT group (29.5 ± 3.2 h, p = 0.009) and required significantly fewer units of urokinase (Schrijver et al. 2015). Technical success was achieved in 84% of patients in the CDT group vs. 75% patients in the UAT group. The combined 30-day death and severe adverse event rate was 19% in the CDT group and 29% in the UAT group. The 30-day patency rate was 82% in the CDT group as compared with 71% in the UAT group (p = 0.35). These differences were not statistically significant.

Alteplase (rt-PA) weight-adjusted doses have ranged in the literature from 0.02 to 0.1 mg/kg/h, whereas non–weight-based doses generally range from 0.25 to 1.0 mg/h, even though higher doses have been reported. In general, the lowest effective dose has not been determined. The recommended maximum dosing was no greater than 40 mg for catheter-directed therapy (Patel et al. 2013). To shorten treatment times, Falkowski et al. (2013) analysed safety and efficacy of ultra-high-dose, short-term thrombolysis in a prospective single-centre study. The outcome of treatment in 97 patients with acute limb ischemia (<14 days) with the use of catheter directed rt-PA infusion was evaluated. The mean total dose of rt-PA was 54.1 mg (50–60 mg) and was administered for a mean of 2.51 h (2–4 h). Thrombolytic success was defined as 95% thrombolysis of an occluded segment with return of antegrade flow. Thrombolytic success was achieved in 83.5%. Overall clinical success was 88.7%. The 30-day amputation-free survival rate was 93.8%. Major bleeding complications occurred in 10 patients (10.3%). There were two deaths (2.1%) and four amputations (4.1%). Amputation-free survival at 2 years was 70%. The study did not support the superiority of ultra-high-dose rt-PA administered over short time frames in limb salvage over other methods of thrombolytic agent administration, but there was an obvious benefit in faster restoration of limb perfusion and greater patient comfort/tolerance.