ENDOTHELIAL DYSFUNCTION AFTER BONE-MARROW TRANSPLANTATION - INCREASE OF SOLUBLE THROMBOMODULIN AND PAI-1 IN PATIENTS WITH MULTIPLE TRANSPLANT-RELATED COMPLICATIONS

Multiple transplant-related complications (MTRC) represent a severe co ndition after bone marrow transplantation (BMT) and are supposed to re flect systemic endothelial damage. Soluble thrombomodulin (sTM) and pl asminogen activator inhibitor type-1 (PAI-1) were investigated as mark ers of endothelial dysfunction in 35 patients after autologous or allo geneic BMT and compared with the occurrence of the typical complicatio ns sepsis, veno-occlusive disease of the liver (VOD). graft-versus-hos t disease (GVHD), and capillary leakage syndrome (CLS). PAI-1 was asse ssed by an assay of functional activity and sTM by antigenic determina tion. In patients who had undergone allogeneic BMT and had no transpla nt-related complications (TRC), PAI-1 peaked on day +14 (20+/-5 units/ mi), and sTM doubled in comparison to the starting range, to 60-80 ng/ ml between days +14 and +49. In contrast, PAI-1 and sTM were unchanged following autologous BMT. PAI-I was increased in sepsis, CLS, and VOD to 39-49 units/ml (p<0.05, compared with patients without TRC), and i n GVHD to 16-47 units/ml (not significant). Soluble TM increased to 63 -309 ng/ml in patients with sepsis, VOD, or CLS (p<0.05? compared with patients without TRC) and to 79-224 ng/ml in GVHD (not significant). The increase of sTM and PAI-1 was also positively correlated to the nu mber of complications, so that in patients with three complications PA I-1 was increased 2.8-fold and sTM 3.5-fold over patients with no comp lications at all. We conclude that endothelial dysfunction is a featur e of VOD, sepsis, CLS, and to lesser extent of GVHD and is worse in pa tients with multiple complications.