用于治疗甲型血友病及抑制物患者的止血疗法联合应用

Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors.

作者信息

Livnat Tami, Budnik Ivan, Levy-Mendelovich Sarina, Avishai Einat, Misgav Mudi, Barg Assaf Arie, Lubetsky Aharon, Brutman-Barazani Tami, Kenet Gili

机构信息

Sackler School of Medicine, Tel Aviv University, Israel; The Israeli National Hemophilia Center, Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel.

Department of Pathophysiology, Sechenov First Moscow State Medical University, Moscow, Russia.

出版信息

Blood Cells Mol Dis. 2017 Jul;66:1-5. doi: 10.1016/j.bcmd.2017.06.005. Epub 2017 Jun 27.

DOI:10.1016/j.bcmd.2017.06.005

PMID:28689155

Abstract

BACKGROUND

Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors.

METHODS

Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII+FEIBA as IV bolus doses.

RESULTS

TG spiking studies showed individual responses not correlated to inhibitor titer. Combinations of agents augmented TG as compared to any single agent, while combined FVIII+FEIBA yielded the highest TG, supporting it as a potential treatment. Following emergent successful surgery of child treated by concomitant FVIII+FEIBA, a total of 396 episodes in 7/15 patients were treated with concomitant FVIII+FEIBA. Five patients were treated for bleeding episodes only, whereas 2 were children undergoing immune tolerance induction (ITI) with FEIBA prophylaxis. Four minor surgeries were performed on FVIII+FEIBA repeated infusions. Neither thrombosis nor any other adverse events were documented.

CONCLUSION

A combination of FVIII+FEIBA may be effective and safe as an alternative treatment option for some high-responding inhibitor patients.

摘要

背景

对甲型血友病（HA）患者及存在抑制物的患者进行治疗应用和监测具有挑战性。在本研究中，对一组患有抑制物的重度HA患者实施了联合FVIII旁路治疗。

方法

将FVIII、重组活化凝血因子VII（rFVIIa）、活化凝血酶原复合物（FEIBA）及其组合体外加入15例存在抑制物的HA患者的血浆中，研究凝血酶生成（TG）情况。部分经历关节积血或需要进行小手术的患者接受了FVIII + FEIBA静脉推注联合给药治疗。

结果

TG加样研究显示个体反应与抑制物滴度无关。与任何单一药物相比，药物组合可增强TG，而FVIII + FEIBA联合用药产生的TG最高，支持其作为一种潜在治疗方法。在一名接受FVIII + FEIBA联合治疗的儿童成功进行急诊手术后，15例患者中的7例共396次发作接受了FVIII + FEIBA联合治疗。5例患者仅接受出血发作治疗，而2例为正在接受免疫耐受诱导（ITI）并预防性使用FEIBA的儿童。对FVIII + FEIBA重复输注进行了4次小手术。未记录到血栓形成或任何其他不良事件。