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Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF-cleaving protease activity

Authors

  • Yoshitaka Mori,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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    • *These authors contributed equally to the manuscript.

  • Hideo Wada,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Esteban C. Gabazza,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Nobuyuki Minami,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Tsutomu Nobori,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Hiroshi Shiku,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Hideo Yagi,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Hiromichi Ishizashi,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • Masanori Matsumoto,

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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    • *These authors contributed equally to the manuscript.

  • Yoshihiro Fujimura

    1. Mie Red Cross Blood Center;
    2. Department of Clinical Laboratory and Second Department of Internal Medicine, Mie University School of Medicine, Tsu City;
    3. Department of Blood Transfusion Medicine and Department of Health Science, Nara Medical University, Kashihara City;
    4. Third Department of Internal Medicine, Mie University School of Medicine, Tsu City, Japan.
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  • ABBREVIATIONS:

    HUS = hemolytic-uremic syndrome; PE = plasma exchange; TTP = thrombotic thrombocytopenic purpura; UL-vWFM(s) = unusually large vWF multimer(s); vWF-CPase = vWF-cleaving protease.

  • Supported in part by research grants from the Japanese Ministry of Health and Welfare for Cardiovascular Diseases (Y.F.) and from the Japanese Ministry of Education Culture and Science (Y.F.).

Address reprint requests to: Hideo Wada, MD, Department of Clinical Laboratory, Mie University School of Medicine, 2-174 Edobashi, Tsu-city, Mie-ken 514-8507, Japan.

Abstract

BACKGROUND: Severe deficiency of vWF-cleaving protease (vWF-CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy.

STUDY DESIGN AND METHODS: The activities of vWF-CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic-uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF-CPase activity.

RESULTS: Eight of nine patients with HUS had more than 40 percent of vWF-CPase activity, whereas one had 28 percent of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF-CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF-CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF-CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF-CPase inhibitor had relapsed and required an immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF-CPase activity.

CONCLUSION: Assays of vWF-CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF-CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF-CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.

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