Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients
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-...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Korean Society of Nephrology
2021-12-01
|
| Series: | Kidney Research and Clinical Practice |
| Subjects: | |
| Online Access: | http://www.krcp-ksn.org/upload/pdf/j-krcp-21-080.pdf |
| _version_ | 1818162519869489152 |
|---|---|
| author | Hoi Woul Lee Jung Nam An Hyung Seok Lee Young Rim Song Hyung Jik Kim Sung Gyun Kim Jwa-Kyung Kim |
| author_facet | Hoi Woul Lee Jung Nam An Hyung Seok Lee Young Rim Song Hyung Jik Kim Sung Gyun Kim Jwa-Kyung Kim |
| author_sort | Hoi Woul Lee |
| collection | DOAJ |
| description | 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. Methods Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. 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 prevalent HD 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 |
| first_indexed | 2024-12-11T16:34:58Z |
| format | Article |
| id | doaj.art-546f4e164bc64d5f956832d795523f39 |
| institution | Directory Open Access Journal |
| issn | 2211-9132 2211-9140 |
| language | English |
| last_indexed | 2024-12-11T16:34:58Z |
| publishDate | 2021-12-01 |
| publisher | The Korean Society of Nephrology |
| record_format | Article |
| series | Kidney Research and Clinical Practice |
| spelling | doaj.art-546f4e164bc64d5f956832d795523f392022-12-22T00:58:29ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322211-91402021-12-0140471272310.23876/j.krcp.21.0806061Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patientsHoi Woul Lee0Jung Nam An1Hyung Seok Lee2Young Rim Song3Hyung Jik Kim4Sung Gyun Kim5Jwa-Kyung Kim6 Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Internal Medicine and Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Internal Medicine and Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Internal Medicine and Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Internal Medicine and Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Republic of KoreaBackground 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. Methods Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. 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 prevalent HD 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 complicationshttp://www.krcp-ksn.org/upload/pdf/j-krcp-21-080.pdfextracellular trapsplatelet factor 4renal dialysisthrombosisvascular access |
| spellingShingle | Hoi Woul Lee Jung Nam An Hyung Seok Lee Young Rim Song Hyung Jik Kim Sung Gyun Kim Jwa-Kyung Kim Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients Kidney Research and Clinical Practice extracellular traps platelet factor 4 renal dialysis thrombosis vascular access |
| title | Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| title_full | Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| title_fullStr | Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| title_full_unstemmed | Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| title_short | Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| title_sort | neutrophil extracellular traps and heparin induced antibodies contribute to vascular access thrombosis in hemodialysis patients |
| topic | extracellular traps platelet factor 4 renal dialysis thrombosis vascular access |
| url | http://www.krcp-ksn.org/upload/pdf/j-krcp-21-080.pdf |
| work_keys_str_mv | AT hoiwoullee neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT jungnaman neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT hyungseoklee neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT youngrimsong neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT hyungjikkim neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT sunggyunkim neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients AT jwakyungkim neutrophilextracellulartrapsandheparininducedantibodiescontributetovascularaccessthrombosisinhemodialysispatients |