重组活化因子 VII 的止血谱。低浓度能否在适应证外的情况下止血？

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

机构信息

Centro de Trombosis de Buenos Aires, Viamonte 2008, 1056 Buenos Aires, Argentina.

出版信息

Thromb J. 2010 May 5;8:8. doi: 10.1186/1477-9560-8-8.

DOI:10.1186/1477-9560-8-8

PMID:20444280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2885319/

Abstract

BACKGROUND

High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro.

METHODS

Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 mug/ml, 2.6 mug/ml, 0.5 mug/ml, 0.25 mug/ml, and 0.125 mug/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM).

RESULTS

In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo-->35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo-->35 min with no effect on PTG but were independent of rFVIIa concentration.

CONCLUSION

Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications.

摘要

背景

高浓度的重组活化因子 VII（rFVIIa）可用于治疗血友病患者的出血。但 rFVIIa 治疗超说明书适应证出血所需的剂量目前尚不清楚。由于凝血酶是主要的止血剂，因此本研究旨在体外观察 rFVIIa 和组织因子（TF）对凝血酶生成（TG）的影响。

方法

采用校准自动血栓描记术检测Lag time（LT）、达峰时间（TTP）、最大 TG（PTG）和 35 分钟时的曲线下面积（AUCo-35 min）来评估 TG。在基础状态下，于富含血小板血浆（PRP）样本中检测 29 名健康志愿者血小板刺激后 5.0μg/ml、2.6μg/ml、0.5μg/ml、0.25μg/ml 和 0.125μg/ml rFVIIa 单独及在正常血小板血浆（PPP）样本中检测 22 名健康志愿者 rFVIIa 与不同浓度 TF（5.0、2.5、1.25 和 0.5 pM）联合时的 TG。

结果

在 rFVIIa 激活的 PRP 中，与基础值相比 TG 显著增加。在 PPP 中，TF 剂量依赖性地显著缩短 LT，并增加 PTG 和 AUCo-35 min。rFVIIa 的加入增加了 TF 缩短 LT 和增加 AUCo-35 min 的作用，对 PTG 没有影响，但与 rFVIIa 浓度无关。