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Recombinant human soluble thrombomodulin counteracts capillary leakage associated with engraftment syndrome

Bone Marrow Transplantation volume 46, pages 616–618 (2011)Cite this article

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Engraftment syndrome (ES), which develops in 7–59% of individuals undergoing hematopoietic SCT (HSCT), is a significant cause of early morbidity and nonrelapse-related mortality.1 This syndrome, characterized by noninfectious fever, skin rash, unexplained weight gain and noncardiogenic pulmonary edema, generally occurs immediately before or at the time of neutrophil engraftment.1 The pathogenesis of ES remains to be fully elucidated, although increased production of proinflammatory cytokines, which can be stimulated by exogenous G-CSF during neutrophil recovery in conjunction with toxicity of the conditioning regimen, is thought to have a role.1 Corticosteroids are used to alleviate the clinical symptoms of ES, but heighten the risk of infection in neutropenic patients.

Recombinant human soluble thrombomodulin (rTM) is composed of the active, extracellular domain of thrombomodulin,2 and inactivates coagulation by binding to thrombin. In addition, the thrombin–rTM complex activates protein C to produce activated protein C, which in the presence of protein S inactivates factors VIIIa and Va, 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.3 Use of rTM for the treatment of DIC has recently been approved in Japan.

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References

  1. Spitzer TR . Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27: 893–898.

    Article  CAS  PubMed  Google Scholar 

  2. Maruyama I . Recombinant thrombomodulin and activated protein C in the treatment of disseminated intravascular coagulation. Thoromb Haemost 1999; 82: 718–721.

    Article  CAS  Google Scholar 

  3. Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5: 31–41.

    Article  CAS  PubMed  Google Scholar 

  4. Schuepbach RA, Feistritzer C, Fernández JA, Griffin JH, Riewald M . Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1. Thromb Haemost 2009; 101: 724–733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Serefhanoglu S, Goker H, Buyukasik Y, Turgut M, Sayinalp N, Haznedaroglu IC et al. Changes in vascular endothelial growth factor, angiopoietins, and Tie-2 levels with G-CSF stimulation in healthy donors. Ann Hematol 2009; 88: 667–671.

    Article  CAS  PubMed  Google Scholar 

  6. Myles T, Nishimura T, Yun TH, Nagashima M, Morser J, Patterson AJ et al. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation. J Biol Chem 2003; 278: 51059–51067.

    Article  CAS  PubMed  Google Scholar 

  7. Abeyama K, Stern DM, Ito Y, Kawahara K, Yoshimoto Y, Tanaka M et al. The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel anti-inflammatory mechanism. J Clin Invest 2005; 115: 1267–1274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

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

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

    T Ikezoe, A Takeuchi, A Taniguchi, K Togitani & A Yokoyama

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  1. T Ikezoe
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  2. A Takeuchi
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  3. A Taniguchi
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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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Ikezoe, T., Takeuchi, A., Taniguchi, A. et al. Recombinant human soluble thrombomodulin counteracts capillary leakage associated with engraftment syndrome. Bone Marrow Transplant 46, 616–618 (2011). https://doi.org/10.1038/bmt.2010.158

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