通过凝血酶生成试验和因子IX活性监测B型血友病患者每周一次的重组因子IX预防治疗。

Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with thrombin generation assay and factor IX activity.

作者信息

Nummi V, Jouppila A, Lassila R

机构信息

Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Coagulation Disorders Unit, Department of Hematology and Comprehensive Cancer Center, Laboratory Services, Helsinki University Hospital, Helsinki, Finland.

出版信息

Int J Lab Hematol. 2017 Aug;39(4):359-368. doi: 10.1111/ijlh.12634. Epub 2017 Apr 13.

DOI:10.1111/ijlh.12634

PMID:28406575

Abstract

INTRODUCTION

Prophylaxis is the recommended treatment mode for severe hemophilia B. However, no single treatment regimen fits for all patients. Once-weekly prophylaxis with high-dose recombinant factor IX (rFIX) is efficacious, nevertheless, laboratory outcomes following 72 h after administration are lacking.

METHODS

In a prospective open-label noncomparative study, 10 severe/moderate (FIX ≤2 IU/dL) adult patients received rFIX dose (60-100 IU/kg) after >72 h washout on two occasions, separated by 7 days. We measured one-stage and chromogenic FIX, ROTEM, and thrombin generation (TG) assay in plasma after washout, 30 min after infusion, and at days 3, 4, and 7.

RESULTS

Median FIX clotting/chromogenic activity increased from 1.5/2.0 to 87/62 IU/dL following rFIX administration, chromogenic assay resulting in 30% lower recovery. Correspondingly TG was severely reduced at baseline and improved at recovery (peak thrombin 6.0 to 54 nm). Standard ROTEM failed to detect FIX deficiency. Both FIX activity and TG remained increased from days 3 to 7, with median trough levels of FIX clotting/chromogenic 3.0/3.0 IU/dL (≥1 IU/dL in all severe patients) and peak thrombin 9.1 nm measured on day 7. FIX and TG assays were equally consistent between weeks 1 and 2.

CONCLUSIONS

Once-weekly rFIX prophylaxis results in favorable laboratory outcome.

摘要

引言

预防是重度乙型血友病推荐的治疗模式。然而，没有一种单一的治疗方案适用于所有患者。高剂量重组凝血因子IX（rFIX）每周一次的预防方案是有效的，不过给药后72小时后的实验室结果尚缺乏。

方法

在一项前瞻性开放标签非对照研究中，10名重度/中度（FIX≤2IU/dL）成年患者在洗脱期>72小时后分两次接受rFIX剂量（60 - 100IU/kg），两次给药间隔7天。我们在洗脱后、输注后30分钟以及第3、4和7天测量血浆中的一期和发色底物法FIX、血栓弹力图（ROTEM）以及凝血酶生成（TG）试验。

结果

给予rFIX后，FIX凝血/发色底物活性中位数从1.5/2.0 IU/dL增加至87/6IU/dL，发色底物法检测到的回收率低30%。相应地，TG在基线时严重降低，恢复时有所改善（凝血酶峰值从6.0到54nM）。标准ROTEM未能检测到FIX缺乏。从第3天到第7天，FIX活性和TG均持续升高，FIX凝血/发色底物活性的中位数谷值为3.0/3.0 IU/dL（所有重度患者均≥1IU/dL），第7天测得的凝血酶峰值为9.1nM。FIX和TG试验在第1周和第2周之间同样具有一致性。