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Successful treatment of transplantation-associated thrombotic microangiopathy with recombinant human soluble thrombomodulin

Bone Marrow Transplantation volume 45, pages 803–805 (2010)Cite this article

Transplantation-associated microangiopathy (TAM) is one of the major complications after hematopoietic stem cell transplantation, with a mortality rate of 60–90%,1 and has some clinical and pathological features similar to clinical syndromes of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome. Clinical manifestations include hemolytic anemia with schistocytes on peripheral blood smears, thrombocytopenia, elevated levels of serum lactate dehydrogenase, and decreased levels of haptoglobin. The etiology of TAM remains to be fully elucidated, but is thought to involve injury to endothelial cells by toxic insults, such as cytotoxic chemotherapy, calcineurin inhibitors, infection and graft-versus-host disease, resulting in a hypercoagulable state and exaggerated cytokine production.1 Although classic idiopathic thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome are successfully treated using plasma exchange, TAM is not. It has recently been reported that rituximab, an anti-CD20 antibody, might be useful for the treatment of both TAM and classic thrombotic thrombocytopenic purpura in which ADAMTS13, a metalloprotease cleaving multimeric von Willebrand factor, is profoundly decreased due to autoantibody formation.2

Recombinant human soluble thrombomodulin (rTM) comprises the active, extracellular domain of thrombomodulin, and inactivates coagulation by binding to thrombin.3 In addition, thrombin–rTM complex activates protein C to produce activated protein C, which inactivates factors VIIIa and Va in the presence of protein S, thereby inhibiting further thrombin formation.3 A recent phase III trial comparing the efficacy and safety of rTM to those of low-dose heparin showed that rTM significantly improved disseminated intravascular coagulation (DIC) associated with hematological malignancies or infections.4 Use of rTM for the treatment of DIC has recently been approved in Japan.

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Acknowledgements

This study was supported, in part, by Kochi University President's Discretionary Grant.

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Authors and Affiliations

  1. Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan

    M Sakai, T Ikezoe, K Bandobashi, K Togitani & A Yokoyama

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  1. M Sakai
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  2. T Ikezoe
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  3. K Bandobashi
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  4. K Togitani
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  5. A Yokoyama
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Correspondence to T Ikezoe.

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Sakai, M., Ikezoe, T., Bandobashi, K. et al. Successful treatment of transplantation-associated thrombotic microangiopathy with recombinant human soluble thrombomodulin. Bone Marrow Transplant 45, 803–805 (2010). https://doi.org/10.1038/bmt.2009.242

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