Plasminogen Activator Inhibitor-1 Confirms the Diagnosis of Hepatic Veno-Occlusive Disease in Patients With Hyperbilirubinemia After Bone Marrow Transplantation

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Abstract
Hepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean ± SD) was significantly (P < .001) elevated in patients with VOD (321.6 ± 161.2 ng/mL) as compared with patients with GVHD (22.8 ± 8.4 ng/mL) or other hepatic damage (32.8 ± 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 ± 230.0 ng/mL in patients with VOD, 41.0 ± 20.6 ng/mL in patients with GVHD, and 44.6 ± 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.