Abstract

The Preventative Effects of Recombinant Thrombomodulin on Transplantation-Associated Coagulopathy after Allogeneic Hematopoietic Stem Cell Transplantation

Shosaku Nomura, Kazuyoshi Ishii, Yoshinobu Maeda, Yuta Katayama, Hideo Yagi, Naohito Fujishima, Shuichi Ota, Masanori Seki, Masaya Okada, Takayuki Ikezoe, Kunio Hayashi, Shinya Fujita, Atsushi Satake, Tomoki Ito, Taiichi Kyo, Yoji Ishida, Shigeru Chiba, Hiroyasu Ogawa, Mitsune Tanimoto and Kenichi Sawada

We investigated the preventive effects of recombinant thrombomodulin (rTM) on Transplantation Associated Coagulopathy (TAC) and TAC-related biomarkers in 271 patients after hematopoietic stem cell transplantation (HSCT). There were no significant differences between the rTM (+) or (-) groups and patient background, types of disease or HSCT regimens. When we examined patients with confirmed complications, all frequencies of aGVHD, VOD and/or TMA, as well as uncomplicated cases were significantly lower in the rTM (+) group. HMGB1 and MCP-1 showed a clear induction after transplantation, which peaked for HMGB1 at day 0 and for MCP-1 at day 7. Although MCP-1 levels did not exhibit significant differences between the two groups, HMGB1 levels in the rTM (+) group showed a significant reduction after day 4 compared with the rTM (-) group. The levels of PAI-1, sE-selectin and sVCAM-1 showed a significant increase in the groups that did not receive rTM. In contrast, the groups that received rTM did not show significant changes and significant differences were found between the two rTM-treated groups. Our multi-institutional study findings suggest that this agent is beneficial as part of preventive therapies for established TAC after HSCT.