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Endothelial dysfunction after bone marrow transplantation: Increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications

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Abstract

 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.

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Received: 27 October 1997 / Accepted: 1 December 1997

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Nürnberger, W., Michelmann, I., Burdach, S. et al. Endothelial dysfunction after bone marrow transplantation: Increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications. Ann Hematol 76, 61–65 (1998). https://doi.org/10.1007/s002770050364

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  • DOI: https://doi.org/10.1007/s002770050364

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