Kidney Res Clin Pract.  2021 Dec;40(4):712-723. 10.23876/j.krcp.21.080.

Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients

Affiliations
  • 1Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
  • 2Department of Internal Medicine and Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea

Abstract

Background
Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events. This prospective observational study included both incident and maintenance HD (MHD) patients.
Methods
Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay; an optical density > 1.8 was regarded as clinically significant. In incident HD patients, we additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed.
Results
The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to MHD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high-sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls.
Conclusion
In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications.

Keyword

Anti-heparin/PF4 antibody; Hemodialysis; Neutrophil extracellular traps; Vascular access; Thromobsis
Full Text Links
  • KRCP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr