Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients
- Author:
Hoi Woul LEE
1
;
Jung Nam AN
;
Hyung Seok LEE
;
Young Rim SONG
;
Hyung Jik KIM
;
Sung Gyun KIM
;
Jwa-Kyung KIM
Author Information
- Publication Type:Original Article
- From:Kidney Research and Clinical Practice 2021;40(4):712-723
- CountryRepublic of Korea
- Language:English
-
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.
