重组活化凝血因子VII（rFVIIa）治疗婴儿出血症。

Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage.

作者信息

Brady Kenneth M, Easley R Blaine, Tobias Joseph D

机构信息

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institute, Baltimore, MD 21287, USA.

出版信息

Paediatr Anaesth. 2006 Oct;16(10):1042-6. doi: 10.1111/j.1460-9592.2006.02039.x.

DOI:10.1111/j.1460-9592.2006.02039.x

PMID:16972833

Abstract

BACKGROUND

Recombinant activated factor VII (rFVIIa) is approved by the FDA for the treatment of bleeding episodes in patients with hemophilia A or B with inhibitors to factor VIII or factor IX. In addition to the FDA-approved indications, rFVIIa has been anecdotally reported effective for profound bleeding episodes in adult patients without hemophilia, and proven beneficial for adults with intracranial hemorrhage. In the pediatric literature, case reports have been made with apparent clinical improvement seen after the use of rFVIIa for acute life-threatening bleeding; however, there are limited data regarding its use in infants<4 months of age. We report our experience with rFVIIa in nine infants with severe hemorrhage of diverse etiologies.

METHODS

This case series of infants under 4 months with coagulopathy and bleeding treated with rFVIIa was collected from two institutions. We report the age, weight and pre-rFVIIa laboratory values of the patients as well as the clinical scenario and outcomes.

RESULTS

The nine infants all suffered acute life-threatening hemorrhage. Two patients were postoperative from cardiac surgery, two with Vitamin K deficiency and intracranial hemorrhage, three with suspected necrotizing enterocolitis and abdominal hemorrhage, and two with pulmonary hemorrhage. The patients ranged in age from 2 days to 4 months, (average age 1 month and average weight 3.3+/-1.0 kg). Seven of the nine patients had frozen plasma, cryoprecipitate, or platelet administration in failed attempts to correct the coagulation defect prior to receiving rFVIIa. The dose range used in this series was 90-100 microg.kg-1, with 90 microg.kg-1 being the most commonly used dose. The average pre-rFVIIa INR was 8.7+/-5.1. Four patients had an immeasurably high INR. All patients had clinical resolution of bleeding after receiving rFVIIa, and seven of nine patients survived.

CONCLUSIONS

rFVIIa is a powerful hemostatic drug whose mechanism of action provides a theoretical specificity to sites of tissue injury. In addition to its FDA-approved uses in hemophiliac patients, this drug has a potential role in the treatment of life-threatening hemorrhage from multiple causes.

摘要

背景

重组活化因子 VII（rFVIIa）已获美国食品药品监督管理局（FDA）批准，用于治疗患有血友病 A 或 B 且体内存在针对因子 VIII 或因子 IX 抑制剂的患者的出血发作。除了 FDA 批准的适应症外，已有轶事报道称 rFVIIa 对非血友病成年患者的严重出血发作有效，并且已证实对患有颅内出血的成年人有益。在儿科文献中，有病例报告显示使用 rFVIIa 治疗急性危及生命的出血后有明显的临床改善；然而，关于其在 4 个月以下婴儿中的使用数据有限。我们报告了我们使用 rFVIIa 治疗 9 例病因各异的严重出血婴儿的经验。

方法

本病例系列收集了两家机构中 4 个月以下患有凝血病和出血并接受 rFVIIa 治疗的婴儿。我们报告了患者的年龄、体重、rFVIIa 治疗前的实验室值以及临床情况和结果。

结果

这 9 例婴儿均遭受急性危及生命的出血。2 例患者为心脏手术后，2 例患有维生素 K 缺乏症并伴有颅内出血，3 例疑似坏死性小肠结肠炎并伴有腹腔出血，2 例伴有肺出血。患者年龄从 2 天至 4 个月不等（平均年龄 1 个月，平均体重 3.3±1.0 kg）。9 例患者中有 7 例在接受 rFVIIa 之前曾尝试输注冷沉淀、纤维蛋白原或血小板以纠正凝血缺陷，但均告失败。本系列使用的剂量范围为 90 - 100 μg·kg-1，其中 90 μg·kg-1 是最常用的剂量。rFVIIa 治疗前的平均国际标准化比值（INR）为 8.7±5.1。4 例患者的 INR 高得无法测量。所有患者在接受 rFVIIa 后出血均得到临床缓解，9 例患者中有 7 例存活。