Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel- Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Institute of Hematology, Lady Davis Carmel Medical Center, Haifa, Israel.
Haemophilia. 2018 Jul;24(4):634-640. doi: 10.1111/hae.13463. Epub 2018 Apr 2.
Drugs targeting factor XI (FXI) shows promising results in reducing postoperative VTE. Recently, researchers have shown that FXI knockout mice had a worse outcome when infected with pathogens for pneumonia, raising concerns about the safety of these drugs.
To investigate the effect of FXI deficiency on the incidence of pneumonia and outcomes of pneumonia in humans.
Using the computerized database of the largest healthcare provider in Israel, we identified adults who were tested for FXI activity between January of 2002 and December of 2014 (n = 10 193). Patients were followed up until December of 2016 for the occurrence of pneumonia and pneumonia requiring hospitalization as a proxy of severe pneumonia.
A total of 8958 (87.9%) had normal FXI activity, 804 (7.9%) had partial deficiency and 431 (4.2%) had severe deficiency; 722 individuals had pneumonia during 70 881 person-years of follow-up (incidence rate: 10.2 per 1000 person-years). Compared to those with normal FXI activity, the adjusted HR for pneumonia was 0.87 (95% CI, 0.67-1.14), and 0.95 (0.69-1.30) for those with partial and severe FXI deficiency, respectively. Overall, 256 individuals were hospitalized for pneumonia during 72 209 person-years of follow-up (incidence rate: 3.5 per 1000 person-years). The corresponding HR for severe pneumonia was 1.0 (0.70-1.48) and 0.86 (0.53-1.40) in those with partial and severe FXI deficiency, respectively. FXI deficiency was not significantly associated with 30-day and 90-day mortality among patients with pneumonia.
FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short-term mortality among patients with pneumonia.
靶向因子 XI（FXI）的药物在降低术后静脉血栓栓塞症方面显示出良好的效果。最近，研究人员发现 FXI 敲除小鼠在感染肺炎病原体时的预后更差，这引起了人们对这些药物安全性的担忧。
探讨 FXI 缺乏对人类肺炎发病率和肺炎结局的影响。
我们使用以色列最大的医疗保健提供者的计算机数据库，确定了 2002 年 1 月至 2014 年 12 月期间接受 FXI 活性检测的成年人（n=10193）。对患者进行随访，直至 2016 年 12 月，以了解肺炎的发生情况以及肺炎需要住院治疗（肺炎严重程度的替代指标）。
共有 8958 人（87.9%）的 FXI 活性正常，804 人（7.9%）存在部分缺乏，431 人（4.2%）存在严重缺乏；722 人在 70881 人年的随访中发生肺炎（发病率：10.2/1000 人年）。与 FXI 活性正常者相比，肺炎的调整 HR 分别为 0.87（95%CI，0.67-1.14）和 0.95（0.69-1.30）。总的来说，256 人在 72209 人年的随访中因肺炎住院（发病率：3.5/1000 人年）。严重肺炎的相应 HR 分别为 1.0（0.70-1.48）和 0.86（0.53-1.40）。FXI 缺乏与肺炎患者的 30 天和 90 天死亡率无显著相关性。
在肺炎患者中，FXI 缺乏与肺炎风险增加、肺炎严重程度或短期死亡率无关。
