Soluble Thrombomodulin Is Associated With Endothelial Dysfunction Syndromes After Pediatric Hematopoietic Stem Cell...

Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by endothelial dysfunction-related syndromes like sinusoidal obstruction syndrome (SOS), capillary leak syndrome (CLS), and severe acute graft-versus-host disease (aGvHD). We investigated soluble thrombomodulin (sTM), an endothelial damage marker, in relation to endothelial dysfunction syndromes after pediatric HSCT.

We measured sTM levels in 113 children before conditioning until Day +180 after HSCT.

Plasma levels of sTM increased significantly after conditioning, particularly in patients receiving busulfan-based regimens (Day +7: 5.0 vs. 7.6 ng/mL, p = 0.0023), and remained elevated until Day +180 after HSCT. Children diagnosed with SOS (n = 51) had significantly higher sTM levels at Days +7 and +14 than children without SOS (Day +7: 7.3 vs. 5.0 ng/mL, p = 0.017). High sTM levels at Day +14 were associated with aGvHD Grade III-IV (n = 8) in multivariable analysis (OR = 3.0 per quartile increase in sTM, p = 0.021). Likewise, children diagnosed with CLS (n = 15) displayed higher sTM levels at Day +7 (5.3 vs. 8.0 ng/mL, p = 0.037), while sTM levels were not associated with engraftment syndrome or bacteremia.

High sTM levels early after pediatric HSCT are associated with the development of SOS, CLS, and severe aGvHD. These results suggest that conditioning-induced endothelial damage and activation of pro-thrombotic environment play key roles in the pathogenesis of these syndromes, indicating that sTM may prove clinically useful to guide early diagnosis and treatment of endothelial damage syndromes.