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Recombinant human soluble thrombomodulin for the treatment of hepatic sinusoidal obstructive syndrome post allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 47, pages 463–464 (2012)Cite this article

Hepatic sinusoidal obstructive syndrome (SOS) is one of the most life-threatening non-hematological complications following myeloablative conditioning regimens for allogeneic hematopoietic SCT (allo-HSCT). SOS may present clinically with rapid and unexplained weight gain, ascites, painful hepatomegaly and jaundice.1 Injury to sinusoidal endothelial cells and hepatocytes by high-dose chemotherapy has been implicated in the pathogenesis of SOS. A number of markers of endothelial injury, including plasma thrombomodulin, tissue factor pathway inhibitor, soluble tissue factor and plasminogen activator inhibitor-1 is reported to be upregulated in patients with SOS. Standard treatment for SOS is supportive management in Japan. Clinical trials using anticoagulants or thrombolytics as treatment options for SOS have not been satisfactory.2, 3, 4 Defibrotide (DF) has been shown to be effective as prophylaxis and in the treatment of SOS,5 but it is not yet available for routine clinical practice in Japan.

Thrombomodulin is a thrombin receptor on the endothelial cell surface that has an important role in regulating intravascular coagulation. Recombinant human soluble thrombomodulin (rTM) inactivates intravascular coagulation by binding to thrombin. A recent phase-III trial comparing the efficacy and safety of rTM with those of low-dose unfractionated heparin showed that rTM significantly improved clinical outcomes in disseminated intravascular coagulopathy (DIC) associated with hematological malignancies or infection.6 A recent report indicates a favorable therapeutic potential of rTM in the management of SOS complicated by DIC;7 however, the efficacy of rTM for the treatment of SOS devoid of DIC remains to be elucidated.

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Authors and Affiliations

  1. Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan

    D Nakamura, M Yoshimitsu, H Kawada, H Inoue, T Kuroki, T Kaieda, S Fujino, H Hamada, S Suzuki, K Matsushita, K Uozumi & N Arima

  2. Division of Hematology and Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    T Kaieda, H Hamada, S Suzuki, K Matsushita, K Uozumi & N Arima

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  1. D Nakamura
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Correspondence to N Arima.

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Nakamura, D., Yoshimitsu, M., Kawada, H. et al. Recombinant human soluble thrombomodulin for the treatment of hepatic sinusoidal obstructive syndrome post allogeneic hematopoietic SCT. Bone Marrow Transplant 47, 463–464 (2012). https://doi.org/10.1038/bmt.2011.103

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