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Fatal intracranial hemorrhage following administration of recombinant thrombomodulin in a patient after cord blood transplantation

Bone Marrow Transplantation volume 46, pages 1030–1031 (2011)Cite this article

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Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic SCT. Although the etiology of SOS remains to be fully elucidated, previous studies suggested that preparative regimens cause damage to the sinusoidal endothelial cells leading to a hypercoagulable state and exaggerated cytokine production.

Recombinant thrombomodulin (rTM), a natural anticoagulant including the active extracellular domain of thrombomodulin, inactivates coagulation by binding to thrombin.1 The thrombin–rTM complex activates protein C, which inactivates factors VIIIa and Va in the presence of protein S.2 rTM was approved in 2008 in Japan based on a phase III clinical trial involving 234 patients with disseminated intravascular coagulation (DIC) associated with solid, hematological malignancies and infections.2 The researchers concluded that use of rTM alleviates bleeding symptoms and improves prognosis of DIC compared with heparin.2 Although little information is available on the efficacy of rTM in patients with diseases other than DIC, several researchers published case reports, which suggest the usefulness of rTM after allo-SCT.3, 4

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Authors and Affiliations

  1. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    M Tsubokura, T Yamashita, L Inagaki, T Kobayashi, K Kakihana, S Wakabayashi, K Ohashi, H Sakamaki & H Akiyama

  2. Department of Hematology and Respiratory Medicine, Kochi University, Kochi, Japan

    T Ikezoe

  3. Third Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan

    H Asakura

  4. Laboratory Molecular Genetics of Hematology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    T Koyama

  5. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    T Tanimoto

  6. Division of Social Communication System for Advanced Clinical Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    M Kami

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  1. M Tsubokura
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  2. T Yamashita
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Correspondence to M Tsubokura.

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Tsubokura, M., Yamashita, T., Inagaki, L. et al. Fatal intracranial hemorrhage following administration of recombinant thrombomodulin in a patient after cord blood transplantation. Bone Marrow Transplant 46, 1030–1031 (2011). https://doi.org/10.1038/bmt.2010.229

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