Recombinant human soluble thrombomodulin (rTM) comprises the active, extracellular domain of thrombomodulin (TM), and inactivates coagulation by binding to thrombin. In addition, the thrombin-rTM complex activates protein C to produce activated protein C (APC), which inactivates factors VIIIa and Va in the presence of protein S, further inhibiting thrombin formation. The use of rTM for the treatment of DIC was approved in Japan in in 2008, and since then it has proved effective in individuals with DIC complicated by a variety of underling diseases including sepsis and acute leukemia. Of note, rTM possesses anti-inflammatory and cytoprotective effects and the use of rTM successfully rescued individuals with sinusoidal obstruction syndrome, engraftment syndrome and transplantation-associated microangiopathy complicated by hematopoietic stem cell transplantation (HSCT). The present study retrospectively investigated whether the use of rTM improved the clinical outcome of individuals who received HSCT in our institution.
From 2001 to 2012, 71 individuals with hematological diseases received HSCT in our institution. Of these, 41 developed coagulopathy in association with various underlying conditions. The patients who developed coagulopathy after 2008 (n=23) were treated by rTM, and the others (n=11) were treated by either heparin and/or antithrombin III concentrate. Seven patients did not receive any anticoagulant therapy. Of note, treatment of coagulopathy by rTM significantly improved clinical outcomes of patients at day 100 and dramatically prolonged their overall survival (p=0.044). Taken together, rTM is useful to improve clinical outcomes of transplant recipients with coagulopathy.
No relevant conflicts of interest to declare.
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