Diagnosis of Hepatic Veno-occlusive Disease by Plasminogen Activator Inhibitor-1 Plasma Antigen Levels: A Prospective Analysis in 350 Allogeneic Hematopoietic Stem Cell Recipients

Abstract

Veno-occlusive disease (VOD) is one of the most serious complications following allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with a high mortality. We conducted a large trial in order to investigate the value of plasminogen activator inhibitor-1 (PAI-1) plasma antigen levels in VOD patients as PAI-1 has been described as a possible diagnostic marker of VOD. In all, 350 stem cell recipients were included in our study. PAI-1 levels were analyzed prior to conditioning therapy and then weekly until eight weeks after HSCT. Transplantation-related complications (TRC) including VOD, microangiopathic hemolytic anemia (MAHA), and graft-versus-host disease (GVHD) were recorded weekly throughout the study. Maximum PAI-1 antigen levels were increased in all patients with VOD (n=15; mean 248 ng/ml; 95% CI 183-314 ng/ml). Maximum PAI-1 levels above 120 ng/ml showed a sensitivity of 100% and a specificity of 30.6% for VOD after HSCT. Our study underlines that maximum PAI-1 plasma antigen levels not exceeding 120 ng/ml have a strong negative predictive value in the diagnosis of VOD and thus represent a helpful non-invasive tool for exclusion of VOD after HSCT.