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Post-Transplant Complications

Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation

Bone Marrow Transplantation volume 29, pages 789–794 (2002)Cite this article

Abstract

Hepatic veno-occlusive disease (VOD) is a life-threatening complication after stem cell transplantation (SCT), characterized by thrombus formation in hepatic venules leading to a symptom triad of hyperbilirubinemia, hepatomegaly, and ascites. Multifactorial defects in the hemostatic system may contribute to its pathogenesis, but its remains to be investigated. Unusually large VWF multimers (UL-VWFMs), produced in and released from vascular endothelial cells, are most biologically active in the interaction with platelets under a high shear stress. UL-VWFMs are cleaved and degraded into smaller VWFMs by a specific liver producing plasma protease, termed VWF-cleaving protease (VWF-CPase), which has recently been identified as a metalloprotease solely produced in liver, termed ADAMTS13. Herein, we studied the correlation between plasma VWF-CPase activity and UL-VWFMs in 21 patients who received SCT, seven patients with VOD and 14 patients without VOD. In non-VOD patients, activities (mean ± 1s.d.) of VWF-CPase were 78 ± 17% of the control before the conditioning regimen, 76 ± 18% on day 0, 64 ± 19% on day 7, 57 ± 23% on day 14, 68 ± 13% on day 21 and 79 ± 19% on day 28 after SCT. The respective values in VOD patients were 32 ± 19%, 27 ± 15%, 18 ± 11%, 22 ± 18%, 26 ± 22% and 12 ± 4%. Thus, VWF-CPase activity was significantly reduced in VOD patients, even before the conditioning regimen, and such a difference was not found in other laboratory tests. However, despite such a clear difference, UL-VWFMs were present in plasmas of both patient groups, together with the increase of VWF antigen and ristocetin cofactor activity. These results indicate that the measurement of this enzyme activity is extremely useful in predicting the occurrence of VOD prior to a demonstration of its direct involvement in its pathogenesis.

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Acknowledgements

We would like to thank Professor Emeritus Koiti Titani (Fujita Health University) for his encouragement and critical reading of this manuscript. The work was supported in part by Grants-in-Aid for Scientific Research (C) from the Japanese Ministry of Education Culture and Science (to YF and MM) and for Blood Coagulation Abnormalities from the Ministry of Health and Welfare of Japan (to YF).

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Authors and Affiliations

  1. Department of Pediatrics, Nara Medical University, Nara, Japan

    Y-D Park & A Yoshioka

  2. Department of Health Science, Nara Medical University, Nara, Japan

    H Ishizashi

  3. Department of Second Internal Medicine, Nara Medical University, Nara, Japan

    H Yagi & Y Yamamoto

  4. Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan

    M Matsumoto & Y Fujimura

  5. Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    K Kawa

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Park, YD., Yoshioka, A., Kawa, K. et al. Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation. Bone Marrow Transplant 29, 789–794 (2002). https://doi.org/10.1038/sj.bmt.1703544

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