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Danaparoid reduces the incidence of hematopoietic stem cell transplantation-associated thrombotic microangiopathy

Bone Marrow Transplantation volume 52, pages 307–309 (2017)Cite this article

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Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) can be a lethal complication seen after stem cell transplantation. The typical pathological features of TA-TMA are arteriole endothelium injury and intra-arteriole thrombosis, whereas the clinical features include hemolytic anemia, exhausting thrombocytopenia and microangiopathy-induced organ damage.1, 2 Endothelial injury as a result of the conditioning regimen, total body irradiation, immunosuppressants, infection and GvHD is thought to contribute to the pathogenesis of TA-TMA.2, 3, 4 According to recent relatively large-scale cohort studies, TA-TMA occurs in 10–25% of patients,3 with a reported mortality rate ranging from 60 to 90%.5, 6, 7 In addition to TA-TMA, hepatic veno-occlusive disease (VOD) is a complication that occurs after hematopoietic stem cell transplantation (HSCT) as a result of endothelial injury. Both TA-TMA and hepatic VOD finally lead to multiorgan failure. The differences between the clinical symptoms of TA-TMA and hepatic VOD are thought to be related to which organs are affected and which parts of the vessels are injured.8, 9 Although there is no established treatment for hepatic VOD, some studies have reported that low-dose heparin prevents the development of hepatic VOD.10, 11 Dalteparin is a type of low molecular weight heparin that is associated with a lower frequency of bleeding complications and is widely used in Japan to prevent the development of hepatic VOD. Danaparoid is a heparin-like protein with a long half-life that exhibits much higher specificity for Factor Xa than low molecular weight heparin. One retrospective study suggested that danaparoid may be a promising candidate for the prophylaxis of VOD after allogeneic HSCT.12 These findings also suggest that danaparoid may be an appropriate drug for the prevention of TA-TMA, in addition to VOD. However, few studies have assessed danaparoid as a prophylactic against TA-TMA after HSCT.

Data from a total of 223 consecutive patients who received allogeneic HSCT for hematological disease at Tokai University Hospital from January 2004 to January 2013 were analyzed retrospectively in the present study. The cohort included 24 patients undergoing a second or more transplantation. For VOD prophylaxis, until March 2008, patients were given dalteparin (3000 IU/24 h continuous iv infusion, from Day 1 to Day 28), whereas from April 2008, patients were given danaparoid (1250 IU, bid, from Day 1 to Day 28). The present study was performed in accordance with the ethics standards of Tokai University School of Medicine. The diagnosis of TA-TMA was based on nine criteria (six laboratory, three clinical), as reported previously.3, 13 The severity of TA-TMA was assessed using Common Toxicity Criteria for Bone and Marrow Transplant Thrombotic Microangiopathy.5

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Acknowledgements

This work was supported by the 2014 Tokai University School of Medicine Research Aid.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    S Machida, M Onizuka, M Toyosaki, Y Aoyama, H Kawai, J Amaki, R Hara, A Ichiki, Y Ogawa, H Kawada & K Ando

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  1. S Machida
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  2. M Onizuka
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  3. M Toyosaki
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Correspondence to M Onizuka.

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Machida, S., Onizuka, M., Toyosaki, M. et al. Danaparoid reduces the incidence of hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Bone Marrow Transplant 52, 307–309 (2017). https://doi.org/10.1038/bmt.2016.270

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