The Clinical Significance and Risk Factors of Anti-Platelet Factor 4/heparin Antibody on Maintenance Hemodialysis Patients: A Two-Year Prospective Follow-up

Delong Zhao,Xuefeng Sun,Hongli Lin,Yang Yang,Zhimin Zhang,Jianrong Zhang,Hanyu Zhu,Lide Lun,Yong Wang,Li Yao,Jijun Li,Mingxu Li,Shimin Jiang,Jiuyang Zhao,Xiangmei Chen,Qi Huang,Masataka Kuwana

doi:10.1371/journal.pone.0062239

Abstract

BackgroundHeparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, identified the related risk factors, and further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients.MethodsThe serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated.Results The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients.ConclusionsA single detection of the anti-PF4/heparin antibody did not predict the occurrence of clinical bleeding, thromboembolic events, or risk of death in the maintenance hemodialysis patients.

Highlights

Hemodialysis is currently the major treatment method for endstage renal disease (ESRD)
Among the 661 maintenance hemodialysis (MHD) patients, 37 subjects tested positive for the anti-platelet factor 4 (PF4)/heparin antibody, of which 33 individuals had a history of heparin exposure, and the remaining four cases had a history of exposure to low-molecular-weight heparin (LMWH) only
The univariate analysis revealed that the positivity rate of the serum anti-PF4/heparin antibody was significantly increased in the MHD patients whose primary diseases were diabetes and elevated diastolic blood pressures (DBPs)

Summary

Introduction

Hemodialysis is currently the major treatment method for endstage renal disease (ESRD). Several studies suggested that the anti-PF4/heparin antibody increases the occurrence of thrombotic events in maintenance hemodialysis (MHD) patients [14,15], but these results were different. The positivity rate of the anti-PF4/heparin antibody in MHD patients from a large sample and from multi-center resources in China is currently not available. Explore the effect of the anti-PF4/ heparin antibody on the occurrence of bleeding, thromboembolic events, and the risk of death in the MHD patients. A prospective and multi-center clinical investigation determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, identified the related risk factors, and further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients

Methods

Results

Discussion

Conclusion