Catheter Directed Thrombolysis for Pediatric Lower Extremity and Inferior Vena Cava Thrombosis

Introduction: The standard recommendation for venous thrombosis in children is anticoagulation alone. However, for acute life, limb, or organ-threatening thrombosis site directed tissue plasminogen activator (tPA) is often used to rapidly restore blood perfusion. While catheter directed thrombolysis (CDT) is a critical tool for severe acute thrombosis, there is limited data available to guide its use in pediatrics. We undertook a study to evaluate the safety and effectiveness of site directed tPA for lower extremity (LE) and inferior vena cava (IVC) thrombosis in children.

Methods: Single-center retrospective medical record review of children (<21 years of age) that received CDT for LE and IVC thrombosis over a 5-year span at Texas Children’s Hospital.

Results: A total of 29 patients were identified that received CDT, either via an overnight infusion or bolus dosing during an interventional procedure, for LE and IVC thrombosis. The median age of the patients evaluated was 15.8 years (0-19.1). Patient characteristics are demonstrated in Table 1. All patients were also treated with a course of anticoagulation. The thromboses represented were extensive, with 93.1% (n=27) being occlusive and affecting multiple venous segments. CDT effectiveness was measured by thrombus resolution at 6 months following initial diagnosis which occurred in 34.5% (n=10) of patients. Rivaroxaban use during the course of anticoagulation was significantly associated with thrombus resolution, which was observed in 75% of patients on rivaroxaban compared to 19% of patients who were not (OR=12.75, 95% CI=2.10-114.33; p<0.01). Patients who took estrogen-containing hormonal therapy prior to diagnosis experienced thrombus resolution at 6 months in 83.3% (n=5) of cases, while those not on hormonal therapy had thrombus resolution 21.7% (n=5) of the time (p=0.01). Non-Hispanic patients (60% white, 20% each African American or Asian) had a trend for higher rate of thrombus resolution (45.5%, n=10) compared to those of Hispanic ethnicity who had no cases of thrombus resolution (p=0.06). The associations of patient and treatment-related characteristics with thrombus resolution is demonstrated in Table 2. CDT safety was measured by bleeding events; there was one major and 3 minor bleeding events that occurred as a complication of CDT. There were no treatment related deaths or post-procedural pulmonary emboli noted. The median drop in hemoglobin following the procedure was 2.3 g/dL, with 24.1% (n=7) requiring a blood transfusion.

Conclusions: The administration of tPA via CDT for LE and IVC thrombosis is safe and effective in pediatrics. Our findings also add to the existing evidence that Hispanic patients affected with vascular disease have worse outcomes (in our case, thrombus resolution) than those patients that identify as non-Hispanic. This may suggest the need for more aggressive interventional and medical approaches in Hispanic children with LE or IVC DVT. Patients that received the anticoagulant rivaroxaban during their treatment course had a 6-fold increase in the rate of thrombus resolution, which remained significant after controlling for ethnicity, suggesting that the medication should be considered for anticoagulation in children affected with extensive LE and IVC thrombosis, especially in the adolescent age range due to ease of dosing regimen. The risk factor of estrogen-containing oral hormonal therapy (a reversible thrombosis risk factor upon cessation of the medication) was also associated with thrombus resolution, suggesting that life-long anticoagulation may not be needed in these patients if estrogen-containing contraceptives are avoided. Future prospective and multi-institutional studies are needed to develop a widely accepted and optimized approach to pediatric thrombolysis.