What is the recommended protocol for administering catheter-directed thrombolysis?

Catheter-Directed Thrombolysis Administration Protocol

Catheter-directed thrombolysis involves direct infusion of thrombolytic agents into the pulmonary arteries or affected veins through a multi-sidehole infusion catheter, using approximately one-fourth the systemic dose (typically 20-24 mg alteplase for PE, or 10 mg for ultra-low-dose protocols) to reduce bleeding risk while achieving similar efficacy to systemic thrombolysis. 1

Patient Selection and Indications

For Pulmonary Embolism

• Intermediate-risk PE with right ventricular dysfunction but without hemodynamic compromise is the primary indication when thrombolysis is deemed appropriate, particularly in centers with appropriate infrastructure and expertise 1
• High-risk PE with hemodynamic compromise may warrant systemic thrombolysis as first-line, though catheter-directed approaches can be considered in centers with expertise, especially for patients at intermediate-to-high bleeding risk 1
• Patients must have proximal thrombi location in pulmonary arteries confirmed by imaging 2

For Deep Vein Thrombosis

• Extensive DVT (such as flegmasia cerulea dolens or axillo-subclavian DVT) where thrombolysis is considered appropriate 1, 3
• Catheter-directed thrombolysis is preferred over systemic thrombolysis for DVT in the United States, where systemic thrombolysis is not standard practice 1

Contraindications to Assess

• Absolute contraindications to thrombolytic therapy (active bleeding, recent intracranial hemorrhage, recent major surgery) 1
• Bleeding risk assessment using validated tools 1

Technical Protocol for Administration

Device Selection

• Standard CDL catheters: Unifuse or Cragg-McNamara (4F-5F catheters) for basic infusion 1
• Ultrasound-assisted CDL: EKOSonic system (5F catheter) for ultrasound-facilitated delivery 1
• Pharmacomechanical CDL: Bashir Endovascular Catheter (7F catheter with nitinol-supported infusion basket) 1

Vascular Access and Catheter Placement

• Access the pulmonary arteries via femoral or jugular venous approach for PE 1
• Position multi-sidehole infusion catheter directly into the thrombus within the main pulmonary arteries 1
• For bilateral PE, bilateral catheter placement is recommended 2
• Confirm catheter position with fluoroscopy or angiography before initiating infusion 1

Alteplase Dosing Protocols

Standard-Dose Protocol (Most Common):

• Total dose: 20-24 mg alteplase administered over 12-24 hours 1
• Infusion rate: Approximately 1 mg/hour per catheter 1
• For bilateral PE: 1 mg/hour per catheter (2 mg/hour total) 2

Ultra-Low-Dose Protocol (Emerging Evidence):

• Total dose: 10 mg alteplase administered over 5 hours 2
• Infusion rate: 1 mg/hour per catheter for bilateral treatment 2
• This protocol showed significant hemodynamic improvement with reduced bleeding risk in intermediate-high-risk PE 2

Reconstitution (per FDA label):

• Reconstitute alteplase to final concentration of 1 mg/mL using Sterile Water for Injection 4
• Do NOT use Bacteriostatic Water for Injection 4
• Mix by gently swirling; complete dissolution within 3 minutes 4
• Use within 8 hours of reconstitution when stored at 2-30°C 4

Concurrent Anticoagulation

• Continue therapeutic anticoagulation with unfractionated heparin or alternative anticoagulant during CDL infusion 1, 3
• For patients with heparin-induced thrombocytopenia, argatroban can be safely used concurrently with CDL 5
• Maintain aPTT at therapeutic range (typically 1.5-2.5 times control) during infusion 1

Monitoring During Infusion

Hemodynamic Monitoring

• Invasive pulmonary artery pressure monitoring at baseline and termination of infusion for PE 2
• Measure systolic and mean pulmonary artery pressures 2
• Assess cardiac index before and after treatment 2
• Monitor for signs of clinical decompensation every 2-4 hours 1

Laboratory Monitoring

• Fibrinogen levels every 4-6 hours during infusion (target >150 mg/dL) 1
• Complete blood count to monitor for bleeding 1
• Renal function monitoring due to risk of rhabdomyolysis, particularly in flegmasia cerulea dolens 3
• No routine coagulation monitoring required if using DOACs post-procedure 6

Clinical Assessment

• Neurological checks every 2 hours to detect intracranial hemorrhage 1
• Monitor access site for bleeding complications 2
• Assess for signs of compartment syndrome in limb ischemia cases 3

Post-Procedure Management

Catheter Removal

• Remove catheters after 12-24 hours (standard protocol) or 5 hours (ultra-low-dose protocol) 1, 2
• Assess hemodynamic response before removal 2
• Apply manual compression to access site for adequate hemostasis 1

Transition to Long-Term Anticoagulation

• For PE: Continue therapeutic anticoagulation for minimum 3 months 1
• For DVT: Minimum 3 months of anticoagulation, with consideration for extended therapy if unprovoked 6
• Preferred agents: Direct oral anticoagulants (apixaban, rivaroxaban) as first-line 6
• Cancer patients: Low molecular weight heparin preferred over warfarin 1, 3

Follow-Up Assessment

• Repeat imaging (echocardiography for PE, venous ultrasound for DVT) at 24 hours to assess clot resolution 1, 2
• Clinical follow-up at 1 month to assess symptom improvement and medication adherence 6
• Evaluate for post-thrombotic syndrome development 6

Safety Considerations and Complications

Major Bleeding Risk

• Symptomatic intracranial hemorrhage: Approximately 3% risk with systemic thrombolysis, potentially lower with catheter-directed approach 1, 7
• Major bleeding: Estimated at 2-7% depending on dose and duration 1
• Access-site bleeding is the most common complication but usually manageable conservatively 2

Other Complications

• Pulmonary artery perforation with lung hemorrhage (rare, <2%) 1
• Distal embolization during catheter manipulation 1
• Pericardial tamponade (rare) 1
• Contrast-induced nephropathy 1
• Hemolysis with certain mechanical devices 1

Alteplase Stability Concerns

• Ultrasound exposure degrades alteplase: Approximately 10% degradation at 2 hours, 20% at 4 hours, 30% at 6 hours 8
• Remaining alteplase retains enzymatic activity despite degradation 8
• This degradation may contribute to the safety profile of ultrasound-assisted CDL 8

Common Pitfalls to Avoid

• Do not delay treatment beyond 4.5 hours for acute ischemic stroke applications, as mortality increases and risk-benefit reverses 7
• Do not use excessive doses: The goal is to use one-fourth the systemic dose to minimize bleeding while maintaining efficacy 1
• Do not ignore bleeding risk stratification: Patients at high bleeding risk may benefit more from reduced-dose protocols 1, 2
• Do not perform CDL without appropriate expertise: Implementation requires specialized laboratory support and trained personnel 1
• Do not forget IVC filter consideration: Evaluate need for temporary IVC filter in patients with contraindication to anticoagulation 3