臨床検査61巻2号

2017年02月発行

今月の特集1 血小板の異常を正しく診断するために

血栓性血小板減少性紫斑病（TTP）

著者： 酒井和哉¹ 松本雅則¹

所属機関： ¹奈良県立医科大学輸血部

ページ範囲：P.132 - P.138

Point

●血栓性血小板減少性紫斑病（TTP）は，von Willebrand因子（VWF）切断酵素であるvon Willebrand因子分解酵素（ADAMTS13）の活性低下に起因する致死的血栓症である．

●溶血性貧血と血小板減少を認める患者ではTTPを疑うことが重要である．同様の病態を呈する鑑別疾患を除外し，臨床的にTTPを疑えば，速やかに血漿交換を行う．

●TTPの確定診断はADAMTS13の活性10％未満によって行われる．

●後天性TTPでは自己抗体（ADAMTS13インヒビター）によってADAMTS13活性が著減する．新鮮凍結血漿（FFP）を置換液とする血漿交換療法およびステロイド投与が標準治療である．

●臨床の現場ではいまだreal timeでのADAMTS13活性測定ができないため，臨床所見に基づいて治療を開始する．

参考文献

1）Goel R, Ness PM, Takemoto CM, et al：Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood　125：1470-1476，2015

2）Furlan M, Robles R, Galbusera M, et al：von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med　339：1578-1584，1998

3）Sadler JE：Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem　67：395-424，1998

4）松本雅則：TMAの診断と治療．臨血　56：2092-2099，2015

5）藤村吉博：トピックス　ADAMTS13．脈管学　51：321-331，2011

6）Uemura M, Tatsumi K, Matsumoto M, et al：Localization of ADAMTS13 to the stellate cells of human liver. Blood　106：922-924，2005

7）Moake JL, Rudy CK, Troll JH, et al：Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med　307：1432-1435，1982

8）Matsumoto M, Bennett CL, Isonishi A, et al：Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan. PLoS One　7：e33029，2012

9）Fujimura Y, Matsumoto M, Isonishi A, et al：Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. J Thromb Haemost　9（Suppl1）：283-301，2011

10）Barcellini W, Fattizzo B：Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. Dis Markers　2015：635670，2015

11）Rock GA, Shumak KH, Buskard NA, et al：Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med　325：393-397，1991

12）Matsumoto M, Yagi H, Ishizashi H, et al：The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Semin Hematol　41：68-74，2004

13）Balduini CL, Gugliotta L, Luppi M, et al：High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol　89：591-596，2010

14）Scully M, Hunt BJ, Benjamin S, et al：Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol　158：323-335，2012

15）Elliott MA, Heit JA, Pruthi RK, et al：Rituximab for refractory and or relapsing thrombotic thrombocytopenic purpura related to immune-mediated severe ADAMTS13-deficiency: a report of four cases and a systematic review of the literature. Eur J Haematol　83：365-372，2009

16）Isonishi A, Bennett CL, Plaimauer B, et al：Poor responder to plasma exchange therapy in acquired thrombotic thrombocytopenic purpura is associated with ADAMTS13 inhibitor boosting: visualization of an ADAMTS13 inhibitor complex and its proteolytic clearance from plasma. Transfusion　55：2321-2330，2015

17）Scully M, McDonald V, Cavenagh J, et al：A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood　118：1746-1753，2011

18）Kokame K, Matsumoto M, Fujimura Y, et al：VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13. Blood　103：607-612，2004

19）Kokame K, Nobe Y, Kokubo Y, et al：FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol　129：93-100，2005

20）Kato S, Matsumoto M, Matsuyama T, et al：Novel monoclonal antibody-based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion　46：1444-1452，2006