Introduction
Catheter-directed thrombolysis (CDT) in pediatric patients represents a specialized intervention for life- and limb-threatening thrombotic events. Due to the lack of well-designed pediatric clinical trials, treatment recommendations have limited evidence and are mainly extrapolated from adult guidelines. This protocol focuses exclusively on pediatric patients, incorporating the latest evidence to provide comprehensive recommendations for catheter-directed thrombolytic therapy in children.

Indications
  • ​Life-threatening thrombosis with hemodynamic compromise
  • Limb-threatening thrombosis with risk of amputation or significant disability
  • Organ-threatening thrombosis (renal, hepatic, pulmonary)
  • Extensive iliofemoral deep vein thrombosis in selected cases
  • Phlegmasia Cerulea Dolens - emergency indication for limb salvage
  • Failed anticoagulation therapy with progression of thrombosis
  • ​CVAD-related thrombosis causing superior or inferior vena cava syndrome
  • Extensive pulmonary embolism with right heart strain
  • Renal vein thrombosis with acute kidney injury
  • Portal vein thrombosis with portal hypertension complications

Contraindication 
Absolute Contraindications
  • Active internal bleeding or recent major hemorrhage
  • Intracranial hemorrhage within 3 months
  • Recent neurosurgery or significant head trauma within 3 months
  • Known intracranial mass lesion or arteriovenous malformation
  • Active seizures or uncontrolled seizure disorder
  • Severe uncontrolled hypertension for age
  • Known bleeding diathesis or coagulopathy
  • Thrombocytopenia (<50,000/mm³ despite transfusion)
  • Recent major surgery within 10 days (relative to bleeding risk)
 
Relative Contraindications (Risk-Benefit Assessment Required)
  • Prematurity with increased bleeding risk
  • Recent minor surgery or invasive procedures
  • Gastrointestinal bleeding history within 3 months
  • Severe hepatic dysfunction
  • Severe renal dysfunction
  • Anticoagulation contraindications
  • Age <28 days (use with extreme caution)
 
Laboratory Contraindications
  • INR >2.0 (unless correctable with FFP)
  • aPTT >2x normal (unless correctable)
  • Fibrinogen <100 mg/dL
  • Hemoglobin <8 g/dL (unless correctable)

Interventional Options 
  • IVC Filter Placement
  • Pharmacological Thrombolysis
  • Mechanical Thrombectomy.​

Pre-Procedure
  • Review pre-procedure imaging to document site and extent of thrombosis.
  • Review indications and contra-indications.
  • Discuss management with hematology. If the plan  is to start an alteplase infusion, the patient will require an ICP/ICU bed. 

Labs
Baseline laboratory Documentation
  • CBC
  • Coagulation and DIC screen
​

Technique
  • Obtain consent for venography/angiography, including follow-up, thrombolysis, thrombectomy, angioplasty and IVC filter placement.
  • Thrombectomy will typically require anesthesia, but in older children an infusion catheter can be placed under local anesthesia.
Initial Imaging
  • Access vessel without thrombosis (e.g. for femoral DVT, access popliteal)
  • Perform arteriography or venography of affected vessels
  • Document extent and location of thrombosis
  • Assess collateral circulation
  • Identify underlying anatomical abnormalities

IVC Filter Placement
  • Insert filter prior to thrombolysis when indicated
  • Avoid placement through affected limb when possible
  • Remove filter as soon as possible. If resolution of thrombus after thrombectomy, remove filter at the end of the procedure.

Thrombolysis Approach
  • Select mechanical, pharmacologic, or combined approach based on clot burden assessment


Pharmacologic Thrombolysis Protocol
Alteplase Preparation and Dosing:
  • Reconstitute with sterile water, can be diluted further with saline.
  • Loading dose: At the discretion of the interventionalist, typically 2-3 mg.

Infusion Dosing Guidelines:
  • Initial rate: 0.06 mg/kg/hr
  • Maximum initial dose: 1 mg/hr (regardless of weight)

Standard Concentrations:
  • Children <30 kg: 10 mg t-PA in 500 mL normal saline (0.02 mg/mL)
  • Children >30 kg: 20 mg t-PA in 1000 mL normal saline (0.02 mg/mL)

Infusion Setup
  • Unifuse catheter can be placed, come in multiple lengths and infusion segment lengths (5-40 cm)
  • If vascular sheath placed, can run saline in side arm of sheath to maintain patency.

Supplemental Heparin Protocol:
  • Can be given peripherally
  • Sub-therapeutic dosing: 10 units/kg/hr (no loading dose)
  • Maximum dose: 500 units/hour regardless of weight

Mechanical Thrombectomy
  • Can be performed as primary treatment or follow 12-24 hours of thrombolytic therapy
  • If primary, lace thrombus with 2-4 mg of Alteplase using 4/5 Kumpe catheter or infusion catheter. Leave to dwell for 5-10 minutes.
  • Penumbra Lightning Bolt: Use largest caliber catheter that can be safely used. For DVT in older children, use 12F system. See manufacturer IFU. Call rep for assistance if not familiar with device.
  • Residual thrombus can then be macerated using angioplasty balloons.
 Pre-procedure venogram demonstrates occlusive thrombus in the right external iliac vein.
An infusion catheter has been placed extending across the length of the thrombus.
Post thrombolysis and mechanical thrombectomy venogram demonstrates patent iliac veins and IVC, with mild residual thrombus.

Complications
Immediate Procedural Complications (0-24 hours):
  • Vascular access complications (arterial puncture, hematoma, vessel injury)
Early Complications (24-72 hours):
  • Local and systemic bleeding (major, minor, site-specific)
  • Intracranial hemorrhage with neurosurgical involvement
  • Catheter-related complications (malposition, occlusion, infection)
Late Complications (>72 hours):
  • Long-term thrombotic complications.
  • Post-thrombotic syndrome.
  • Vessel-related complications and interventions.

Post-Procedure
The post-procedure thrombolysis plan is included in EPIC,

Clinical Monitoring
Every 15 minutes during infusion:
  • Neurological assessment: Age-appropriate neurological checks
  • Bleeding evaluation: All access sites, IV sites, surgical sites
  • Vital signs: Blood pressure, heart rate, respiratory rate
  • Extremity assessment: Color, temperature, perfusion, pulses
  • NPO while alteplase is being infused.

​Hourly assessments:
  • Comprehensive neurological exam in verbal children
  • Pain assessment using age-appropriate scales
  • Urine output monitoring (goal >1 mL/kg/hour)
  • Signs of systemic bleeding​

Laboratory Monitoring
Every 4-6 hours:
  • Complete blood count with differential
  • Comprehensive metabolic panel
  • Coagulation studies: PT/INR, aPTT
  • Fibrinogen level (maintain >100 mg/dL, >150 mg/dL in neonates)
  • D-dimer trending
Additional monitoring:
  • Type and crossmatch maintained
  • Arterial blood gas if respiratory concerns
  • Lactate if perfusion concerns
Dose Modifications
  • Reduce t-PA by 50% if fibrinogen <100 mg/dL
  • Hold therapy if fibrinogen <75 mg/dL despite cryoprecipitate
  • Platelet transfusion if count <100,000/mm³
  • Cryoprecipitate if fibrinogen persistently low

Pediatric Bleeding Management
Major Bleeding Protocol
Immediate interventions:
  • Stop all thrombolytics and heparin immediately
  • Activate massive transfusion protocol if available
  • Notify pediatric intensivist and hematology immediately
  • Consider surgical consultation for accessible bleeding
Reversal agents:
  • Aminocaproic acid: 100 mg/kg IV loading dose, then 30 mg/kg/hour
  • Cryoprecipitate: 10-15 mL/kg to raise fibrinogen >150 mg/dL
  • Fresh frozen plasma: 15-20 mL/kg for coagulopathy
  • Platelet transfusion: 10-15 mL/kg to maintain >100,000/mm³
Minor Bleeding Management
  • Local measures: Direct pressure, topical hemostatic agents
  • Continue monitoring with increased frequency
  • Consider dose reduction rather than discontinuation
  • Maintain fibrinogen >100 mg/dL with cryoprecipitate
  • Continuous monitoring of the vital signs per ICU/ICP protocol for arterial thrombosis. For non-critical venous thrombosis, monitoring can be performed on the hematology floor.
  • Continuous monitoring of the affected limb for signs of underperfusion including color, temperature, perfusion, limb girth, etc.
  • ​Only essential venipunctures should be obtained while t-PA is being infused. Avoid IM injections.
Hypersensitivity Reactions
  • Stop infusion immediately
  • Antihistamines: Diphenhydramine 1 mg/kg IV
  • Corticosteroids: Methylprednisolone 2 mg/kg IV
  • Epinephrine if anaphylaxis suspected

 Follow-up
Intermediate Care (1-7 days)
  • Transition to therapeutic anticoagulation
  • Imaging follow-up within 24-48 hours
  • Mobilization as clinically appropriate
  • Family education for home monitoring
Long-term Follow-up
  • Hematology follow-up at 1 week, 1 month, 3 months
  • Imaging surveillance at 3 and 6 months
  • Developmental assessment in younger children
  • Thrombophilia workup when appropriate​​
References
  1. Monagle P, Cuello CA, Augustine C, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv. 2018;2(22):3292-3316.
  2. Brandão LR, Albisetti M, Halton J, et al. IPOG/ISTH pediatric venous thromboembolism guidelines: management of central venous catheter-associated thrombosis. Thromb Haemost. 2023;123:1-12.
  3. Wang M, Hays T, Balasa V, et al. Low-dose tissue plasminogen activator thrombolysis in children. J Pediatr Hematol Oncol. 2003;25(5):379-86.
  4. Dix D, Andrew M, Marzinotto V, et al. The use of low molecular weight heparin in pediatric patients: a prospective cohort study. J Pediatr. 2000;136(4):439-45.
  5. Tarango C, Manco-Johnson MJ. Pediatric thrombolysis: a practical approach. Front Pediatr. 2017;5:260.
  6. Gupta AA, Leaker M, Andrew M, et al. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr. 2001;139(5):682-8.
  7. Rivkin MJ, deVeber G, Ichord RN, et al. Thrombolysis in Pediatric Stroke study. Stroke. 2015;46(3):880-5.
  8. Mitchell LG, Goldenberg NA, Male C, et al. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost. 2011;9(9):1856-8.
  9. de Alarcon PA, Donohue KM, Lorts A, et al. Low-dose systemic thrombolytic therapy for deep vein thrombosis in pediatric patients. Pediatr Blood Cancer. 2012;59(5):837-42.
  10. Male C, Kenet G, Holzhauer S, et al. The NEOCLOT study - a randomized controlled trial on catheter-directed thrombolysis versus anticoagulation alone in neonates and infants with venous thrombosis: study protocol for a randomized controlled trial. Trials. 2017;18(1):583.
  11. Monagle P, Chan AKC, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e737S-e801S.
  12. Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood. 2007;110(1):45-53.
  13. Park CK, Paes BA, Nagel K, et al. Neonatal central venous catheter thrombosis: diagnosis, management and outcome. Blood Coagul Fibrinolysis. 2014;25(2):97-106.
  14. Reiter PD, Wathen B, Valuck RJ. Cost-effectiveness of low-dose vs standard-dose alteplase for treatment of catheter occlusion in pediatric patients. Ann Pharmacother. 2002;36(11):1692-8.
  15. Lehman RA, Kim DH, Gobin YP. Treatment of vascular thrombosis in the pediatric population. Semin Intervent Radiol. 2017;34(1):44-53.
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