Effectiveness of Intraarterial Plasminogen Application in Combination with Percutaneous Transluminal Angioplasty (PTA) or Catheter Assisted Lysis (CL) in Patients with Chronical Peripheral Occlusive Disease of the Lower Limbs (POL)
Authors: Tilsner V. , Witte G. 
Published: April 2009

The accepted correct procedure for treating occlusive arterial diseases includes surgical disobstruction, CL as well as PTA. Combined non-surgical strategies are effective in about 60 % of these patients. However, a high risk of rethrombosis despite from the prophylaxis with anticoagulants like heparin or antiplatelet drugs like ASA is proven, especially in patients with multi-segmental stenosis as well as in patients with extensive narrowing of the arteries. In these cases primary lesions (endangitis obliterans) or secondary lesions of the endothelium cause local depletion of plasminogen in the endothelium. Independent of the method used for reopening the vessel in these patients, a significant progression of the vessel disease and a high rethrombosis rate during longterm follow-up is observed. These results lead us to apply plasminogen locally to decrease the rate of rethrombosis. In patients suffering from stage III – IV (La Fontaine) including patients with multi-segmental stenosis as well as extended narrowing of the artery, PTA in combination with CL was performed. The catheter was placed as near as possible to the thrombus. In some cases the fibrinolyticum’ could be injected directly into the thrombus. In these cases a bolus of 4,000 U/ml was locally infused, otherwise 1.0–1.5 million U urokinase per 24 hrs. were locally infused with heparin. In 28 % (22 patients) no sufficient clinical response occurred using this combined therapy and plasminogen was applied locally. The following criteria supported our decision to include the patients in this study: 1. Insufficient response occurring after 12–24 hrs. of local infusion. 2. Following 6 bolus injections no reopening of the vessel occured within 60 minutes or the clinical response was insufficient due to rethrombosis. 3. Insufficient effects of lysis therapy after 2 hours and contraindication for a systemic fibrinolytic therapy (e.g. hypertension, age, etc.). 1,000 U plasminogen per ml were infused locally or 2,000 U up to 5,000 U plasminogen (in 5 to 10 ml 0.9 % saline) were infused slowly (2–4 minutes infusion time) into the catheter in these patients 10 minutes after unsuccessful treatment with local urokinase therapy. Five minutes after administering plasminogen local intraarterial fibrinolytic therapy with urokinase was continued. No severe side effects due to this therapy were observed, although some patients suffered from acute pains in the peripheral segments of the arteries occuring immediately after infusion of plasminogen. In 16 of 22 patients a complete recanalization occurred and in 3 patients a satisfying clinical improvement was observed. In these patients no amputation was necessary and the residual walking capacity improved significantly (3 to 30 m before therapy, more than 500 m post-therapy). In 3 patients out of this group an additional TPA and CL treatment was necessary within 3 to 6 months; in 2 patients this treatment was successful. In only 3 of these patients did no clinical response occur when plasminogen was applicated intraarterially. Summarizing the results local application of plasminogen improves the efficacy of intraarterial CL particularly in patients suffering from extended or multi-segmental arterial stenosis of the lower limb arteries. Systemic substitution therapy with plasminogen increases in our experience the rate of bleeding complications and is less successful than the local application of plasminogen in combination with CL.