Deep Vein Thrombosis of Lower Extremity: Direct Intraclot Injection of Alteplase Once Daily with Systemic Anticoagulation—Results of Pilot Study

Abstract

Conclusion: Daily intraclot injection of a venous thrombus with alteplase can be an alternative to continuous infusion thrombolytic therapy for treatment of deep venous thrombosis (DVT). Summary: An alternative to continuous infusion of lytic agents is to intermittently lace the thrombus with a thrombolytic agent that binds to fibrin in the clot and is rapidly cleared from the general circulation. This can allow the thrombolytic agent to work at the site where it is needed but minimize the duration of systemic exposure to the thrombolytic agent. This study prospectively evaluated the outcome of patients with acute DVT in the lower extremity treated with daily lacing of the thrombus with alteplase. Alteplase has a high fibrin affinity and therefore continuous infusion of the thrombolytic agent is not required. Twenty patients with first-onset acute DVT were treated with direct daily lacing of the thrombus with alteplase with a maximum daily dosage of 50 mg/leg and a maximum of four treatments. Catheters were left in place between treatments. Patients were also systemically anticoagulated fully. Patients underwent ventilation perfusion (V/Q) scans, which were performed before treatment and during thrombolytic therapy. The study comprised 13 men and 7 women, aged 18 to 79 years. Antegrade blood flow was restored throughout the deep venous system in 16 patients (80%) during thrombolytic therapy. After 6 months of anticoagulation, 18 patients (90%) had complete resolution of symptoms. There was rapid clearance of circulating alteplase and recovery of plasminogen activator inhibitor-1 levels by pharmacokinetic studies ≤2 hours after termination of alteplase treatment. A 40% incidence of pulmonary embolism was documented by V/Q scanning before treatment and a 15% incidence of asymptomatic pulmonary embolism during thrombolytic therapy. No clinically important pulmonary embolism or serious bleeding occurred during thrombolytic therapy. During the mean follow-up of 3.4 years, no post-thrombotic syndrome or recurrent DVT developed in any patient. Comment: The most obvious practical advantage of this approach is that patients do not require intensive monitoring of a continuous infusion of a thrombolytic agent. However, intermittent administration of alteplase directly into the thrombus does require a substantial time commitment. Procedure times for the first treatment of an uncomplicated iliofemoral DVT were 1.5 hours. If there was extensive calf DVT, initial procedure times could be doubled or almost tripled. Procedure times for subsequent treatments are shorter because catheters are left in place after the initial treatment and can be exchanged using standard guidewire techniques. Overall, it appears if one has the catheter skills and time, intermittent administration of a thrombolytic agent directly into the clot may be a viable alternative to more standard continuous infusion techniques.