Abstract No. 5: Once Daily, Low Dose Alteplase Intraclot Injection Thrombolytic Therapy for Acute Venous Thrombosis

Abstract

Although once daily infiltration of venous thrombi with alteplase (recombinant tissue plasminogen activator or r-tPA) without continuous infusion of additional alteplase has been shown to be effective for large doses of alteplase (20 -50 mg/day), pharmacokinetic data suggest that effective thrombolysis can be achieved with lower doses. To test this hypothesis, we report treatment of subclavian, jugular, and/or central vein thrombosis (SJ-CVT) and treatment of acute deep vein thrombosis of the lower extremity (DVT-LE) using substantially lower doses of alteplase. Patients: Twenty six patients with SJ-CVT less than 4 weeks old, and 16 patients with DVT-LE less than 2 weeks old were treated. One patient had bilateral DVT-LE due to IVC filter and IVC thrombosis. Technique: Alteplase was diluted with normal saline to a concentration of 0.1 mg/ml. The entire thrombus is “laced” with alteplase by an interventional radiologist using forceful hand injection through pulse spray catheters. For SJ-CVT, the maximum daily dose was 4 mg/day, and for DVT-LE, a maximum of 10 mg/leg/day. A venogram is obtained the day after each treatment. The treatment is repeated once daily until antegrade flow is restored or until a maximum of 4 doses have been given. Balloon angioplasty was used to treat strictures. Uncovered stents were placed only in iliac veins. Pharmacokinetic data was obtained in about a third of patients. Full systemic anticoagulation was used in almost all cases. Patients with SJ-CVT who opted for outpatient thrombolytic therapy received anticoagulation with enoxaparin. For the 26 SJ-CVT patients, average dose of alteplase was 3.6 mg/day for an average of 2 treatments (days), restoring patency in 19 (73%) patients. The average daily dose of alteplase for the 16 patients (17 limbs) with DVT-LE was 7.5 mg/day for an average of 2.5 days of treatment, restoring full venous patency in 15 (94%) patients and partial patency in the remaining patient. There were no significant bleeding complications, and no need for blood transfusions. Our study indicates safe and effective thrombolysis can be effected using much smaller doses of alteplase than previously reported.