Plasma von Willebrand Factor Propeptide Level in Patients with Thrombotic Thrombocytopenic Purpura_West China Medical Journal

Authors：

HUANG Xiaoou , JI Jie , TANG Yun , LU Zhongping , LIU Ting

Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610044, P. R. China;

Corresponding author：

Keywords：

血栓性血小板减少性紫癜; 血管性血友病因子前肽; 内皮细胞

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【摘要】　目的　探讨血栓性血小板减少性紫癜（thrombotic thrombocytopenic purpura，TTP）患者血管内皮损伤程度，以及不同类型TTP之间血管内皮损伤差异性。　方法　纳入2005年4月-2010年12月特发性TTP患者17例（A组），继发性TTP患者15例（B组），骨髓移植相关TTP患者2例（C组），疑似TTP患者11例（D组），共45例；另选取健康体检志愿者为对照组10例（E组）。采用双夹心酶联免疫吸附试验测定血管性血友病因子前肽（von Willebrand factor propeptide，vWFpp）水平。　结果　 vWFpp水平为其与正常混合血浆的比值， A组为2.2，B组为2.34，C组为2.795，D组为1.72，E组为1.08。A、B、C、D组患者vWFpp水平与E组比较，差异有统计学意义（P lt;0.05），A、B、C、D组间比较，差异无统计学意义（P gt;0.05）。　结论　 TTP患者vWFpp水平明显增高，提示血管内皮损伤明显，但vWFpp水平不能用于鉴别TTP类型。
【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.

Citation： HUANG Xiaoou,JI Jie,TANG Yun,LU Zhongping,LIU Ting. Plasma von Willebrand Factor Propeptide Level in Patients with Thrombotic Thrombocytopenic Purpura. West China Medical Journal, 2011, 26(11): 1642-1645. doi: Copy

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.	韩纪举, 任道凌, 陈彬, 等. 血管性血友病因子前肽双抗体夹心法检测及临床应用[J]. 中华检验医学杂志, 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, 魏文宁. 血栓性血小板减少性紫癜患者血管性血友病因子裂解酶活的分析[J]. 血栓与止血杂志, 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. 　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. 　韩纪举, 任道凌, 陈彬, 等. 血管性血友病因子前肽双抗体夹心法检测及临床应用[J]. 中华检验医学杂志, 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, 魏文宁. 血栓性血小板减少性紫癜患者血管性血友病因子裂解酶活的分析[J]. 血栓与止血杂志, 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.

West China Medical Journal

Plasma von Willebrand Factor Propeptide Level in Patients with Thrombotic Thrombocytopenic Purpura

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