Related Experiment Video
Updated: Feb 12, 2026
Experimental Model to Evaluate Resolution of Pneumonia
Published on: February 17, 2023
Factor XI deficiency is not associated with an increased risk of pneumonia and pneumonia-related mortality
O Salomon1, M Preis2, A Abu Shtaya3
1Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel- Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Introduction:
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.
Aim:
To investigate the effect of FXI deficiency on the incidence of pneumonia and outcomes of pneumonia in humans.
Methods:
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.
Results:
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.
Conclusion:
FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short-term mortality among patients with pneumonia.
Insights
Factor XI (FXI) deficiency does not increase pneumonia risk or severity in humans. This study found no significant association between FXI levels and pneumonia outcomes or mortality.
Area of Science:
- Hematology
- Infectious Diseases
- Pharmacology
Background:
- Factor XI (FXI) targeted drugs show promise for preventing VTE.
- Recent studies suggest FXI deficiency may worsen pneumonia outcomes in mice.
- This raises safety concerns for FXI inhibitors regarding infection risk.
Purpose of the Study:
- To evaluate the association between FXI deficiency and pneumonia incidence in humans.
- To assess the impact of FXI deficiency on pneumonia severity and mortality.
Main Methods:
- Retrospective cohort study of 10,193 adults with FXI activity testing.
- Analysis of pneumonia occurrence and hospitalization rates over a median follow-up of 6.7 years.
- Adjusted hazard ratios (HR) were calculated for pneumonia and severe pneumonia.
Main Results:
- FXI deficiency was not linked to an increased risk of pneumonia (HR 0.87-0.95).
- No significant association was found between FXI deficiency and pneumonia hospitalization (HR 1.0-0.86).
- FXI deficiency did not impact 30-day or 90-day mortality in pneumonia patients.
Conclusions:
- FXI deficiency is not associated with increased pneumonia risk or severity.
- FXI deficiency does not appear to negatively impact short-term survival in pneumonia patients.
- Findings suggest FXI inhibitors may be safe concerning pneumonia risk.
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