Can recombinant thrombomodulin play a preventive role for veno-occlusive disease after haematopoietic stem cell transplantation?

Dear Sirs, Although haematopoietic stem cell transplantation (HSCT) is being used for haematopoietic reconstitution following highdose chemotherapy for malignancy, it involves some serious transplant-related complications (1, 2), such as graft-versushost disease (GVHD) and vascular disorders (such as veno-occlusive disease (VOD), pulmonary vasculopathy, thrombotic microangiopathy (TMA), and capillary leak syndrome) (3–5). The authors have advocated “SIGHT” as a keyword for the complications after HSCT. This acronym comprises the capital letters of five complications after HSCT, namely sinusoidal obstruction syndrome (SOS same as VOD), Infection, GVHD, haemophagocytic syndrome (HPS) and TMA. In particular, VOD and TMA are involved in abnormalities of the haemostasis and coagulation system. Injury to sinusoidal endothelial cells and hepatocytes by chemotherapy appears to be the primary event in the pathogenesis of VOD (6, 7). A number of markers for endothelial injury and adhesion molecules are upregulated in patients with VOD, including plasma thrombomodulin (TM), E-selectin, tissue factor, tissue factor pathway inhibitor and plasminogen activator inhibitor (8). Consequently, some biomarkers of endothelial injury are essential for predicting the development of VOD (9). On the other hand, heparin is often used for the prevention of VOD, since it is an anticoagulant therapy (10). However, in a previous report by the authors, elevation of soluble (s) E-selectin and sVCAM-1 was observed despite heparin administration to prevent VOD after HSCT (11). Therefore, heparin may be inadequate for the prevention of VOD. In the present study, we measured sE-selectin and sVCAM-1 after HSCT using recombinant (r) TM (12, 13) instead of heparin. In addition, tumour necrosis factor (TNF)-α, high mobility group Correspondence to: Prof. Shosaku Nomura First Department of Internal Medicine Kansai Medical University, Osaka, Japan E-mail: [email protected]