Regular ArticleThe prevalence of antibodies to the platelet factor 4 -heparin complex and association with access thrombosis in patients on chronic hemodialysis
Introduction
Heparin-induced thrombocytopenia (HIT) is a serious complication of systemic heparin therapy. Exposure to heparin can trigger an immune response resulting in the production of antibodies formed against a platelet factor 4-heparin complex. [1], [2]. IgG platelet factor 4-heparin (PF4-H) antibodies have been associated with the development of venous or arterial thrombosis. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing PF4-H antibodies.
The maintenance of adequate vascular access is crucial to patient survival on hemodialysis. Complications related to vascular access account for 20 to 25% of all hospitalizations in dialysis patients [3], [4] and cost over one billion dollars annually in the United States [3]. Thrombosis is the leading cause of arteriovenous fistula and graft failure [4].
PF4-H antibodies have been suggested as a possible cause of dialysis access thrombosis [5]. Studies to date have generated conflicting results. Whereas some suggest the presence of an association between vascular access thrombosis and PF4-H antibodies [6], [7], [8], [9], others do not [10], [11]. These studies were case reports or case series describing the occurrence or specific management of heparin-induced thrombocytopenia in dialysis patients. We there sought to determine the prevalence and association of PF4-H antibodies with vascular access thrombosis in a large case-control study of hemodialysis patients.
Section snippets
Study design and participants
A case-control study evaluating thrombophilia and dialysis access thrombosis was recently completed at the Ottawa Hospital [12]. Sera from the 419 patients who participated in this study were used to measure PF4-H antibodies. The study was approved by the Ottawa Hospital Research Ethics Board.
Adult patients on maintenance hemodialysis from three in-center and five satellite units associated with the Ottawa Hospital, a Canadian academic health science center, were approached for study
Results
Eight hundred and forty-eight patients were screened for enrollment. Patients were excluded for the following reasons: fistula or graft never created or never functioned (n = 345); access created but not yet used (n = 21). Of the 482 eligible patients, 63 refused or were unable to consent leaving 419 participants in the study. There were 107 cases with access thrombosis and 312 controls that never had access thrombosis [12].
The baseline characteristics of the cases and controls are depicted in
Discussion
To our knowledge, this is the largest and most comprehensive examination of the association between PF4-H antibodies and dialysis access thrombosis. In the present analysis, hemodialysis with repeated exposure to systemic UFH was associated with a moderately elevated prevalence of PF4-H antibodies. Although the results of previous research suggest a link between the presence of PF4-H antibodies and an increase in hypercoagulability leading to thrombotic complications [6], [7], [8], [9], [10],
Acknowledgements
This study was funded by the Physician' Services Incorporated Foundation (Grant #R05–28). Dr. Rodger is a recipient of the Maureen Andrew New Investigator Award from the Heart and Stroke Foundation of Canada. We thank the staff and patients from the dialysis units that participated in the study. Special thanks to Dr. Paul Greenman for his helpful comments on an earlier version of this manuscript.
References (31)
Vascular Access for Hemodialysis
Kidney Int
(1999)- et al.
Heparin-induced thrombocytopenia in hemodialysis patients
Am J Kidney Dis
(1996) - et al.
Heparin-induced antibodies as a risk factor for thromboembolism and haemorrhage in patients undergoing chronic haemodialysis
Lancet
(1996) - et al.
Platelet count, anti-heparin/platelet factor 4 antibodies and tissue factor pathway inhibitor plasma antigen level in chronic dialysis
Thromb Res
(1998) - et al.
Heparin-associated antiplatelet antibodies increase morbidity and mortality in hemodialysis patients
Surgery
(2004) - et al.
No significant improvement in diagnostic specificity of an anti-PF4/polyanion immunoassay with use of high heparin confirmatory procedure
J Thromb Haemost
(2006) - et al.
Laboratory testing for the antibodies that cause heparin-induced thrombocytopenia: how much class do we need?
J Lab Med
(2005) - et al.
A diagnostic test for heparin-induced thrombocytopenia
Blood
(1986) - et al.
Immunology and Clinical Importance of antiphospholipid Antibodies
Adv Immunol
(1991) - et al.
Heparin-induced thrombocytopenia: what the serologist have taught us
J Lab Clin Med
(1996)