• 四川大學(xué)華西醫(yī)院血液科（成都，610044）;

【摘要】　目的　 探討血栓性血小板減少性紫癜（thrombotic thrombocytopenic purpura，TTP）患者血管內(nèi)皮損傷程度，以及不同類型TTP之間血管內(nèi)皮損傷差異性。　方法　 納入2005年4月-2010年12月特發(fā)性TTP患者17例（A組），繼發(fā)性TTP患者15例（B組），骨髓移植相關(guān)TTP患者2例（C組），疑似TTP患者11例（D組），共45例；另選取健康體檢志愿者為對照組10例（E組）。采用雙夾心酶聯(lián)免疫吸附試驗(yàn)測定血管性血友病因子前肽（von Willebrand factor propeptide，vWFpp）水平。　結(jié)果　 vWFpp水平為其與正?；旌涎獫{的比值， A組為2.2，B組為2.34，C組為2.795，D組為1.72，E組為1.08。A、B、C、D組患者vWFpp水平與E組比較，差異有統(tǒng)計(jì)學(xué)意義（P lt;0.05），A、B、C、D組間比較，差異無統(tǒng)計(jì)學(xué)意義（P gt;0.05）。　結(jié)論　 TTP患者vWFpp水平明顯增高，提示血管內(nèi)皮損傷明顯，但vWFpp水平不能用于鑒別TTP類型。
【Abstract】　Objective　 To explore the severity of endothelium injury in patients with thrombotic thrombocytopenic purpura (TTP) and the differences among different subtypes of TTP.　Methods　 The clinical data of 45 patients with TTP diagnosed between April 2005 and December 2010 were retrospectively analyzed. von Willebrand factor propeptide (vWFpp) was measured by sandwich ELISA in 17 patients with idiopathic TTP (group A), 15 patients with secondary TTP (group B), 2 patients with transplantation associated TTP (group C), 11 patients with suspected TTP (group D) and 10 control healthy volunteers (group E).　Results　 Median times of vWFpp of the five groups were 2.2, 2.34, 2.795, 1.72, and 1.08 respectively. Plasma vWFpp levels of the first four groups didn′t differ much between each other (P lt;0.05), but the differences were significant compared with the data in the control group (P gt;0.05).　Conclusions　 Significantly increased vWFpp level in patients with TTP indicates obvious endothelium injury. Nevertheless, it could not be used to differentiate TTP types.

引用本文： 黃曉鷗,季杰,唐韞,盧忠平,劉霆. 血栓性血小板減少性紫癜患者血管性血友病因子前肽水平的研究. 華西醫(yī)學(xué), 2011, 26(11): 1642-1645. doi: 復(fù)制

1. 　Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura[J]. Blood, 2008, 112(1): 11-18.
2. 　Burns ER, Zucker-Franklin D. Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells[J]. Blood, 1982, 60(4): 1030-1037.
3. 　Lotta LA, Lombardi R, Mariani M, et al. Platelet reactive conformation and multimeric pattern of von Willebrand factor in acquired thrombotic thrombocytopenic purpura during acute disease and remission[J]. J Thromb Haemost, 2011, 9(9): 1744-1751.
4. 　韓紀(jì)舉, 任道凌, 陳彬, 等. 血管性血友病因子前肽雙抗體夾心法檢測及臨床應(yīng)用[J]. 中華檢驗(yàn)醫(yī)學(xué)雜志, 2006, 29(3): 226-228.
5. 　van Mourik JA, Romani de Wit T. Von Willebrand factor pro-peptide in vascular disorders[J]. Thromb Haemost, 2001,86(1): 164-171.
6. 　Chauhan AK, Walsh MT, Zhu G, et al. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis[J]. Blood, 2008, 111(7): 3452-3457.
7. 　王雅丹, 魏文寧. 血栓性血小板減少性紫癜患者血管性血友病因子裂解酶活的分析[J]. 血栓與止血雜志, 2005, 11(5): 200-202.
8. 　Mori Y, Wada H, Gabazza EC, et al. Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF-cleaving protease activity[J]. Transfusion, 2002, 42(5): 572-580.
9. 　Borchiellini A, Fijnvandraat K, ten Cate JW, et al. Quantitative analysis of von Willebrand factor propeptide release in vivo: Effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans[J]. Blood, 1996, 88(8): 2951-2958.
10. 　Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura[J]. Nature, 2001, 413(6855): 488-494.
11. 　Schneppenheim R, Budde U. von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein[J]. J Thromb Haemost, 2011, 9 (Suppl 1): 209-215.
12. 　Luken BM, Turenhout EA, Hulstein JJ, et al. The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura[J]. J Thromb Haemost, 2005, 93(2): 267-274.
13. 　Soejima K, Nakagaki T. Interplay between ADAMTS13 and von Willebrand factor in inherited and acquired thrombotic microangiopathies[J]. Semin Hematol, 2005, 42(1): 56-62.
14. 　Klaus C, Plaimauer B, Studt JD, et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura[J]. Blood, 2004, 103(12): 4514-4519.
15. 　Romani De Wit T, Fijnheer R, Brinkman HJ, et al. Endothelial cell activation in thrombotic thrombocytopenic purpura (TTP): a prospective analysis[J]. Br J Haematol, 2003, 123(3): 522-527.
16. 　Gadisseur A, Hermans C, Berneman Z, et al. Laboratory diagnosis and molecular classification of von Willebrand disease[J]. Acta Haematol, 2009, 121(2-3): 71-84.
17. 　Wagner DD, Fay PJ, Sporn LA, et al. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells[J]. Proc Natl Acad Sci,1987,84(7):1955-1959.
18. 　Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients[J]. Blood, 2003, 102(1): 60-68.
19. 　Nangaku M, Nishi H, Fujita T. Pathogenesis and prognosis of thrombotic microangiopathy[J]. Clin Exp Nephrol, 2007, 11(2): 107-114.
20. 　Veyradier A, Obert B, Houllier A, et al. Specific von Willebrandfactor-cleaving protease in thrombotic microangiopathies: a study of 111 cases[J]. Blood, 2001, 98(6): 1765-1772.
21. 　Zheng XL, Kaufman RM, Goodnough LT, et al. Effect of plasma exchangeon plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura[J]. Blood, 2004, 103(11): 4043-4049.
22. 　Kremer Hovinga JA, Studt JD, Lammle B. The von Willebrandfactor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP)[J]. Pathophysiol Haemost Thromb, 2003, 33(5-6): 417-421.
23. 　Bohm M, Betz C, Miesbach W, et al. The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine[J]. Br J Haematol, 2005, 129(5): 644-652.
24. 　Kim JW, Kim I, Oh KH, et al. Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the 10-year experience of a single center[J]. Hematology, 2011, 16(2): 73-79.
  1. 1. 　Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura[J]. Blood, 2008, 112(1): 11-18.
  2. 2. 　Burns ER, Zucker-Franklin D. Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells[J]. Blood, 1982, 60(4): 1030-1037.
  3. 3. 　Lotta LA, Lombardi R, Mariani M, et al. Platelet reactive conformation and multimeric pattern of von Willebrand factor in acquired thrombotic thrombocytopenic purpura during acute disease and remission[J]. J Thromb Haemost, 2011, 9(9): 1744-1751.
  4. 4. 　韓紀(jì)舉, 任道凌, 陳彬, 等. 血管性血友病因子前肽雙抗體夾心法檢測及臨床應(yīng)用[J]. 中華檢驗(yàn)醫(yī)學(xué)雜志, 2006, 29(3): 226-228.
  5. 5. 　van Mourik JA, Romani de Wit T. Von Willebrand factor pro-peptide in vascular disorders[J]. Thromb Haemost, 2001,86(1): 164-171.
  6. 6. 　Chauhan AK, Walsh MT, Zhu G, et al. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis[J]. Blood, 2008, 111(7): 3452-3457.
  7. 7. 　王雅丹, 魏文寧. 血栓性血小板減少性紫癜患者血管性血友病因子裂解酶活的分析[J]. 血栓與止血雜志, 2005, 11(5): 200-202.
  8. 8. 　Mori Y, Wada H, Gabazza EC, et al. Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF-cleaving protease activity[J]. Transfusion, 2002, 42(5): 572-580.
  9. 9. 　Borchiellini A, Fijnvandraat K, ten Cate JW, et al. Quantitative analysis of von Willebrand factor propeptide release in vivo: Effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans[J]. Blood, 1996, 88(8): 2951-2958.
  10. 10. 　Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura[J]. Nature, 2001, 413(6855): 488-494.
  11. 11. 　Schneppenheim R, Budde U. von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein[J]. J Thromb Haemost, 2011, 9 (Suppl 1): 209-215.
  12. 12. 　Luken BM, Turenhout EA, Hulstein JJ, et al. The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura[J]. J Thromb Haemost, 2005, 93(2): 267-274.
  13. 13. 　Soejima K, Nakagaki T. Interplay between ADAMTS13 and von Willebrand factor in inherited and acquired thrombotic microangiopathies[J]. Semin Hematol, 2005, 42(1): 56-62.
  14. 14. 　Klaus C, Plaimauer B, Studt JD, et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura[J]. Blood, 2004, 103(12): 4514-4519.
  15. 15. 　Romani De Wit T, Fijnheer R, Brinkman HJ, et al. Endothelial cell activation in thrombotic thrombocytopenic purpura (TTP): a prospective analysis[J]. Br J Haematol, 2003, 123(3): 522-527.
  16. 16. 　Gadisseur A, Hermans C, Berneman Z, et al. Laboratory diagnosis and molecular classification of von Willebrand disease[J]. Acta Haematol, 2009, 121(2-3): 71-84.
  17. 17. 　Wagner DD, Fay PJ, Sporn LA, et al. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells[J]. Proc Natl Acad Sci,1987,84(7):1955-1959.
  18. 18. 　Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients[J]. Blood, 2003, 102(1): 60-68.
  19. 19. 　Nangaku M, Nishi H, Fujita T. Pathogenesis and prognosis of thrombotic microangiopathy[J]. Clin Exp Nephrol, 2007, 11(2): 107-114.
  20. 20. 　Veyradier A, Obert B, Houllier A, et al. Specific von Willebrandfactor-cleaving protease in thrombotic microangiopathies: a study of 111 cases[J]. Blood, 2001, 98(6): 1765-1772.
  21. 21. 　Zheng XL, Kaufman RM, Goodnough LT, et al. Effect of plasma exchangeon plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura[J]. Blood, 2004, 103(11): 4043-4049.
  22. 22. 　Kremer Hovinga JA, Studt JD, Lammle B. The von Willebrandfactor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP)[J]. Pathophysiol Haemost Thromb, 2003, 33(5-6): 417-421.
  23. 23. 　Bohm M, Betz C, Miesbach W, et al. The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine[J]. Br J Haematol, 2005, 129(5): 644-652.
  24. 24. 　Kim JW, Kim I, Oh KH, et al. Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the 10-year experience of a single center[J]. Hematology, 2011, 16(2): 73-79.