Berntorp E
Malmö Centre for Thrombosis and Haemostasis, Malmö University Hospital, Malmö, Sweden.
Haemophilia. 2007 Dec;13 Suppl 5:69-72. doi: 10.1111/j.1365-2516.2007.01577.x.
We and others have previously shown that inhibitor containing plasma from patients with congenital haemophilia A sometimes reacts less with von Willebrand factor (VWF) containing concentrates compared with highly purified plasma-derived or recombinant factor VIII (FVIII) concentrates. To further substantiate the haemostatic role of a variation in inhibitor reactivity with different FVIII concentrates, we compared the inhibitor titres from 11 plasma samples against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested: Fandhi (Grifols) which contains VWF with a final ratio of approximately 1 (VWF IU per IU FVIII:C); Haemate (CSL Behring) with a ratio of 2.5 and Haemofil M (Baxter), a monoclonal antibody-purified concentrate containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer (Bayer) containing no VWF was included in the panel. A statistically significant difference in measured titres against the four concentrates was found. The inhibitor titre needed to inhibit 50% maximum thrombin generation was lowest for Kogenate Bayer and highest and similar for Fandhi and Haemate. This study confirms the results from previous research regarding variation of inhibitor reactivity against different concentrates and further shows that the VWF containing concentrates Fandhi and Haemate added to FVIII-deficient plasma with the presence of inhibitor generate more thrombin than do the purified concentrates Haemofil M and Kogenate Bayer. A further interesting aspect could be that bypass therapy may have an increased efficacy when infused together with FVIII concentrates containing VWF. However, the clinical implications of all these findings in vitro need to be established.
我们和其他研究人员之前已经表明，与高度纯化的血浆源性或重组凝血因子VIII（FVIII）浓缩物相比，先天性A型血友病患者含抑制剂的血浆有时与含血管性血友病因子（VWF）的浓缩物反应较弱。为了进一步证实不同FVIII浓缩物的抑制剂反应性变化在止血中的作用，我们比较了11份血浆样本针对一组FVIII浓缩物的抑制剂效价，并将效价与抑制凝血酶生成的能力进行关联。测试了三种血浆源性浓缩物：Fandhi（Grifols），其VWF最终比例约为1（每IU FVIII:C含1 IU VWF）；Haemate（CSL Behring），比例为2.5；以及Haemofil M（百特），一种仅含微量VWF的单克隆抗体纯化浓缩物。此外，该组中还包括不含VWF的重组FVIII浓缩物Kogenate Bayer（拜耳）。发现针对这四种浓缩物测得的效价存在统计学显著差异。抑制50%最大凝血酶生成所需的抑制剂效价，Kogenate Bayer最低，Fandhi和Haemate最高且相近。本研究证实了先前关于不同浓缩物抑制剂反应性变化的研究结果，并进一步表明，在存在抑制剂的情况下，向FVIII缺乏的血浆中添加含VWF的浓缩物Fandhi和Haemate比纯化浓缩物Haemofil M和Kogenate Bayer产生更多的凝血酶。另一个有趣的方面可能是，旁路治疗与含VWF的FVIII浓缩物一起输注时，疗效可能会提高。然而，所有这些体外研究结果的临床意义仍有待确定。
