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

Hematopoietic Stem Cell Transplantation (HSCT) involves specific serious transplant-related complications [1,2], and recovery from these complications is vital for achieving a successful HSCT outcome. Therefore, taking steps to mitigate coagulationand Graft-Versus Host Disease (GVHD)-related complications following HSCT is very important. Several interactions between coagulation-related blood components and the fibrinolytic systems are involved in the progression of vascular angiopathy. Notably, plasminogen activator inhibitor (PAI)-1 plays an important role in the pathophysiology of many vascular abnormalities [3]. Recombinant thrombomodulin (rTM) is composed of the active extracellular domain of TM. Like membranebound TM, rTM binds to thrombin to inactive coagulation. The thrombin–rTM complex activates protein C to produce active protein C (APC), which in the presence of protein S inactivates factors VIIIa and Va, thereby inhibiting further thrombin formation [4]. Therefore, rTM might be useful for transplantation-associated coagulopathy (TAC) after HSCT. Indeed, there are some reports of the efficacies of therapies for TAC, such as veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) [5,6]. However, the preventive effects of rTM for TAC or TAC-related biomarkers following HSCT are poorly understood. Here, we investigated the preventive effects of rTM for TAC and TAC-related biomarker levels after HSCT. To our knowledge, this report of a multi-institutional joint study is the first to document the potential ability of rTM to prevent TAC after HSCT. The study cohort included 271 patients who underwent SCT between June 2011 and February 2014 at one of 24 institutions in Japan. All patients received allogeneic SCT (Table 1). The 161 male and 110 female allogeneic SCT patients ranged in age from 7 to 71 years (median: 45 years). Patient diagnoses consisted of 102 acute myeloid leukemia cases, 63 acute lymphoblastic leukemia cases, 38 myelodysplastic syndrome cases and 68 other diagnoses. Conditioning was applied as follows: total body irradiation for 175 patients and non-total body irradiation for 96 patients. The donor sources for transplantation were 139 bone marrow cells, 57 peripheral blood stem cells and 75 cord blood cells (Table 1). Written informed consent was obtained from all patients who were registered by faxing documents to Kansai Medical University prior to SCT. The rTM, consisting of daily doses of 380 units/kg (Asahi Kasei Pharma, Tokyo, Japan), was administered as a preventive therapy for TAC. This protocol was Abstract