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 condition after bone marrow transplantation (BMT) and are supposed to reflect systemic endothelial damage. Soluble thrombomodulin (sTM) and plasminogen activator inhibitor type-1 (PAI-1) were investigated as markers of endothelial dysfunction in 35 patients after autologous or allogeneic BMT and compared with the occurrence of the typical complications sepsis, veno-occlusive disease of the liver (VOD), graft-versus-host disease (GVHD), and capillary leakage syndrome (CLS). PAI-1 was assessed by an assay of functional activity and sTM by antigenic determination. In patients who had undergone allogeneic BMT and had no transplant-related complications (TRC), PAI-1 peaked on day +14 (20 +/- 5 units/ml), 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-1 was increased in sepsis, CLS, and VOD to 39-49 units/ml (p < 0.05, compared with patients without TRC), and in 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 number of complications, so that in patients with three complications PAI-1 was increased 2.8-fold and sTM 3.5-fold over patients with no complications at all. We conclude that endothelial dysfunction is a feature of VOD, sepsis, CLS, and to lesser extent of GVHD and is worse in patients with multiple complications.
Nürnberger
W
W
Department of Pediatric Hematology and Oncology, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Michelmann
I
I
Burdach
S
S
Göbel
U
U
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D019559:Capillary Leak Syndrome / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006086:Graft vs Host Disease / Q000503:physiopathology; D006504:Hepatic Veno-Occlusive Disease / Q000503:physiopathology; D006801:Humans; D007223:Infant; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D018805:Sepsis / Q000503:physiopathology; D012995:Solubility; D018180:Thrombomodulin / Q000378:metabolism*
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin