Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

Exclusion Criteria

• •1. Known contraindication(s) to the use of tPA, including:
• •* active internal bleeding;
• •* history of cerebrovascular accident;
• •* recent intracranial or intraspinal surgery or trauma;
• •* intracranial neoplasm, intracranial arteriovenous malformation or intracranial aneurysm;
• •* known bleeding diathesis;
• •* and/or severe uncontrolled hypertension
• •2. Body weight \>/= 100th percentile or BMI \> 30
• •3. Known cystic fibrosis
• •4. Currently receiving dornase-alfa and/or inhaled unfractionated or low molecular weight heparin and/or a direct acting oral anticoagulant (e.g., dabigatran, rivaroxaban)
• •* Inhaled unfractionated or low molecular weight heparin must be discontinued at least 72h. Inhaled dornase alfa should be discontinued no later than the time of the start of enrollment in the treatment phase. If the patient is receiving inhaled tPA, this regimen must be discontinued and transitioned to the inpatient dosing regimen (5mg Q6h) of study drug.
• •* Direct acting oral anticoagulants must be discontinued one week prior to the start of enrollment in the treatment phase.
• •5. Protein losing enteropathy
• •6. Liver dysfunction (defined as ≥ 3X the normal levels of one or both liver transaminases, AST and AST)
• •• Transaminase levels acquired within the last 9 months can be used to assess liver function. If previously normal and there is no clinical indication that liver function has worsened, the patient can be enrolled. If there are no transaminase values within the last 9 months, they need to be acquired as part of screening
• •7. Need for concomitant intravenous or sub-cutaneous anti-coagulation with resulting anti- Xa levels \> 0.5 (low molecular weight heparins) or \> 0.3 (unfractionated heparin)
• •8. International normalized ratio (INR) \> 2.0 if not receiving warfarin
• •9. Patients being actively treated for thrombosis
• •10. Concomitant use of a thienopyridine class antiplatelet agent (e.g., clopidogrel)
• •11. A platelet count of \< 100,000 platelets/µL
• •12. A hematocrit \<30%
• •13. Gross hematuria on screening urinalysis
• •14. Pregnant or lactating women (negative pregnancy test required for girls/women of childbearing potential at the time of inhaled tPA administration). All women of child- bearing potential must be willing to practice appropriate contraception throughout the study.
• •15. Subjects who are known positive for, or are hospitalized with COVID-19 caused by the new coronavirus, SARS CoV-2, at the start of the treatment phase.
• •16. Suspected or active concurrent infectious illness.
• •1. Exceed the 100th percentile for body weight or have a BMI greater than 30.
• •2. History of post-operative chylothorax following any palliation surgery (except for PLE controls).
• •3. Known liver dysfunction per medical record review (e.g., defined as ≥ 3X the normal levels of one or both liver transaminases \[ALT \& AST\])
• •4. COVID-19 positive within the last 14 days prior to the scheduled visit and/or the presence of symptoms consistent with COVID-19 at the time of the visit
• •5. Suspected or active concurrent infectious illness