von Willebrand factor and its propeptide: the influence of secretion and clearance on protein levels and the risk of venous thrombosis
von Willebrand factor and its propeptide: the influence of secretion and clearance on protein levels and the risk of venous thrombosis
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DOI：
10.1111/j.1538-7836.2006.02273.x
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发表时间：
2006-12-01
影响因子：
10.4
通讯作者：
Eikenboom, H. C. J.
中科院分区：
文献类型：
--
作者：
Nossent, A. Y.;Van Marion, V.;Eikenboom, H. C. J.
背景和目的：因子（F）VIII水平升高与血栓形成风险增加相关。FVIII水平主要由血管性血友病因子（VWF）决定。我们研究了分泌和清除率对VWF抗原（VWF：Ag）升高和血栓形成风险的贡献。VWF与其前肽以等摩尔量分泌，前肽具有较短的半衰期。VWF前肽可用作VWF分泌的量度并允许估计VWF半衰期。方法和结果：我们在莱顿血栓形成研究中测定了VWF前肽、VWF：Ag、FVIII：Ag和FVIII活性（FVIII：C）。在对照组中，高VWF前肽与高VWF：Ag、FVIII：Ag和FVIII：C相关。与成熟的VWF：Ag相比，VWF前肽不受血型的影响。使用ELISA为基础的测定，我们已经表明，VWF前肽缺乏ABO抗原。男性中的水平较高，并随年龄增长而增加。长VWF半衰期也与高VWF：Ag、FVIII：Ag和FVIII：C相关。VWF半衰期受血型影响（O型个体为10 h，非O型个体为12 h），但不受性别影响，仅受年龄影响轻微。VWF前肽在血栓形成患者中高于对照组。患者和对照组的VWF半衰期相似（分别为11.4和11.1 h）。结论：分泌和清除率是VWF和FVIII水平的重要决定因素。然而，主要是分泌增加引起的高VWF和FVIII水平似乎与血栓形成有关。ABO血型影响VWF的清除率而不是VWF的分泌率。
Background and objectives: Elevated levels of factor (F)VIII are associated with an increased risk of thrombosis. FVIII levels are determined mainly by von Willebrand factor (VWF). We have investigated the contribution of secretion and clearance rates to the elevated VWF antigen (VWF:Ag) and to the risk of thrombosis. VWF is secreted in equimolar amounts with its propeptide, which has a shorter half-life. VWF propeptide can be used as a measure of VWF secretion and allows estimation of the VWF half-life. Methods and results: We have measured VWF propeptide, VWF:Ag, FVIII:Ag and FVIII activity (FVIII:C) in the Leiden Thrombophilia Study. In controls, high VWF propeptide was associated with high VWF:Ag, FVIII:Ag and FVIII:C. In contrast to mature VWF:Ag, VWF propeptide was not influenced by blood groups. Using an ELISA-based assay we have shown that VWF propeptide lacks ABO antigens. Levels were higher in men and increased with age. A long VWF half-life was also associated with high VWF:Ag, FVIII:Ag and FVIII:C. The VWF half-life was influenced by blood group (10 h in O vs. 12 h in non-O individuals), but not by sex, and only slightly by age. VWF propeptide was higher in thrombosis patients than in controls. The VWF half-life was similar in patients and controls (11.4 and 11.1 h, respectively). Conclusions: Both secretion and clearance rates are important determinants of VWF and FVIII levels. However, mainly high VWF and FVIII levels caused by increased secretion seem to be associated with thrombosis. ABO blood group influences the clearance rates of VWF rather than VWF secretion rates.