Positives

• Lab studies show defibrotide suppressed COVID-19 plasma-induced caspase 8 activation in microvascular endothelial cells by approximately 60%, modulating TNF-alpha, IL-17, and endothelin pathways implicated in PASC vasculopathy PMC.
  
  
• A 2025 review identifies defibrotide as having pleiotropic anti-inflammatory, antithrombotic, and fibrinolytic properties that may help reverse the endotheliitis described in Long COVID MDPI.
  
  

Negatives

• Evidence in Long COVID is limited to mechanistic and ex-vivo work; no published randomized clinical trial has shown symptomatic improvement in PASC patients on defibrotide PubMed.
  
  

Hurdles & Side Effects

• Defibrotide (Defitelio) is FDA-approved only for hepatic veno-occlusive disease in transplant patients, costs roughly $160,000 per course, and requires inpatient IV infusion every 6 hours, putting outpatient Long COVID use essentially out of reach ScienceDirect.