Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel.
Thromb Haemost. 2019 Dec;119(12):1927-1932. doi: 10.1055/s-0039-1696685. Epub 2019 Sep 7.
Factor XI (FXI) deficiency is a rare autosomal bleeding disorder. The rarity of spontaneous bleeding and absence of optimal tools to predict the bleeding risk in FXI-deficient patients hamper the standardization of prophylactic treatment enabling them to undergo major surgeries without blood products.
We explored the effectiveness of a single and very low dose of recombinant factor VIIa (rFVIIa) along with tranexamic acid (TXA) as prophylactic treatment for FXI-deficient patients undergoing various types of surgery at various sites of injury. We studied the potential use of thrombin generation (TG) as a surrogate tool for predicting thrombogenicity.
Our cohort consisted of 10 patients with severe FXI deficiency undergoing 12 interventions. Patients received a single dose of 10 to 15 μg/kg rFVIIa at the end of surgery in addition to TXA initiated 2 hours before surgery at the dose of 4 g/day for 3 to 5 days. TG was tested before and 30 minutes after rFVIIa administration.
All operations were uneventful and none of the patients bled excessively or required blood products. No thrombotic event was reported, and the postoperative hospitalization duration was comparable to that of patients without bleeding disorders. TG performed at the peak of rFVIIa was below the curve of healthy controls, thus confirming that the administered dose was not thrombogenic.
A single very low dose of rFVIIa along with TXA is a simple and safe treatment to control hemostasis in severe FXI-deficient patients undergoing diverse type of surgical procedure at various sites.
因子 XI（FXI）缺乏是一种罕见的常染色体出血性疾病。由于自发性出血罕见，且缺乏预测 FXI 缺乏患者出血风险的最佳工具，因此无法标准化预防性治疗，使他们能够在不使用血液制品的情况下接受主要手术。
我们探索了单次和极低剂量的重组因子 VIIa（rFVIIa）联合氨甲环酸（TXA）作为预防治疗各种类型手术和不同损伤部位的 FXI 缺乏患者的有效性。我们研究了血栓生成（TG）作为预测血栓形成性的替代工具的潜在用途。
我们的队列包括 10 名严重 FXI 缺乏症患者，共进行了 12 次干预。患者在手术结束时接受 10 至 15μg/kg rFVIIa 的单次剂量，此外，在手术前 2 小时开始以 4g/天的剂量使用 TXA 3 至 5 天。在 rFVIIa 给药前和给药后 30 分钟测试 TG。
所有手术均顺利进行，无患者过度出血或需要血液制品。未报告血栓事件，术后住院时间与无出血性疾病的患者相似。rFVIIa 峰值时的 TG 低于健康对照组的曲线，这证实了给予的剂量没有血栓形成性。
单次极低剂量的 rFVIIa 联合 TXA 是一种简单且安全的治疗方法，可控制严重 FXI 缺乏症患者在不同部位进行各种类型手术时的止血。
