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六种血管性血友病因子浓缩物的体外比较评估

A comparative in vitro evaluation of six von Willebrand factor concentrates.

作者信息

Lethagen S, Carlson M, Hillarp A

机构信息

Department of Coagulation Disorders, Malmo University Hospital, Lund University, Malmo, Sweden.

出版信息

Haemophilia. 2004 May;10(3):243-9. doi: 10.1111/j.1365-2516.2004.00893.x.

Abstract

UNLABELLED

The efficacy of von Willebrand factor (VWF) concentrates for treatment of von Willebrand disease (VWD) is dependent on their content of VWF and factor VIII (FVIII).

STUDY OBJECTIVES

To measure the content and quality of VWF and FVIII in six VWF concentrates: Haemate-P (Aventis Behring), Immunate (Baxter Bioscience), Koate (Bayer Corp.), 8Y (BPL), Innobrand (LFB) and Facteur Willebrand (LFB).

METHODS

The VWF antigen content (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen-binding activity (VWF:CB), VWF multimers with electrophoresis and densitometry, FVIII activity and total protein content.

RESULTS

Specific activity (VWF:RCo/total protein) varied considerably (4.7-129.5 IU mg(-1)). Activity measures, VWF:RCo and VWF:CB, correlated well, but we found no correlation between any of these and VWF:Ag. The content of high-molecular weight multimer (HMWM) was normal or close to normal in Haemate-P, Innobrand and Facteur Willebrand, moderately reduced in Koate and 8Y, and significantly reduced in Immunate. The HMWM content correlated significantly with the VWF:RCo/VWF:Ag ratio. Only Haemate-P, Innobrand and Facteur Willebrand had VWF:RCo/VWF:Ag ratios >0.7. We found large differences in the content of FVIII and in the FVIII/VWF:RCo ratio. Facteur Willebrand had the lowest (0.02) and Immunate the highest (6.00) ratio.

CONCLUSION

Treating physicians must be aware of the large differences between different VWF concentrates and the potential clinical implications. Concentrates lacking HMWM are probably less efficient for mucosal bleedings. FVIII is most important for surgical bleedings, but concentrates with high FVIII/VWF-ratio may induce very high FVIII levels with increased risk of thrombosis. A low FVIII content may be preferable except in case of acute surgery.

摘要

未标记

血管性血友病因子(VWF)浓缩物治疗血管性血友病(VWD)的疗效取决于其VWF和凝血因子VIII(FVIII)的含量。

研究目的

测定六种VWF浓缩物中VWF和FVIII的含量及质量:海莫莱士(拜耳先灵)、艾美赛珠单抗(百特生物科技)、科跃(拜耳公司)、8Y(BPL)、英诺品牌(LFB)和血管性血友病因子(LFB)。

方法

VWF抗原含量(VWF:Ag)、瑞斯托霉素辅因子活性(VWF:RCo)、胶原结合活性(VWF:CB)、通过电泳和光密度测定法检测VWF多聚体、FVIII活性和总蛋白含量。

结果

比活性(VWF:RCo/总蛋白)差异很大(4.7 - 129.5 IU mg⁻¹)。活性指标VWF:RCo和VWF:CB相关性良好,但我们发现这些指标与VWF:Ag之间均无相关性。海莫莱士、英诺品牌和血管性血友病因子中高分子量多聚体(HMWM)含量正常或接近正常,科跃和8Y中中度降低,艾美赛珠单抗中显著降低。HMWM含量与VWF:RCo/VWF:Ag比值显著相关。只有海莫莱士、英诺品牌和血管性血友病因子的VWF:RCo/VWF:Ag比值>0.7。我们发现FVIII含量及FVIII/VWF:RCo比值存在很大差异。血管性血友病因子的比值最低(0.02),艾美赛珠单抗的比值最高(6.00)。

结论

治疗医生必须意识到不同VWF浓缩物之间的巨大差异及其潜在的临床意义。缺乏HMWM的浓缩物可能对黏膜出血的疗效较差。FVIII对手术出血最为重要,但FVIII/VWF比值高的浓缩物可能会导致FVIII水平非常高,血栓形成风险增加。除急性手术外,低FVIII含量可能更可取。

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