The prevalence of antibodies to the platelet factor 4 -heparin complex and association with access thrombosis in patients on chronic hemodialysis.
BACKGROUND
Heparin-induced thrombocytopenia is a serious complication that can lead to thrombocytopenia, venous and arterial thrombosis. Patients with this disorder develop antibodies to the platelet factor 4-heparin (PF4-H) complex. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing PF4-H antibodies. We sought to determine the prevalence of PF4-H antibodies in a large cohort of patients on chronic hemodialysis and to evaluate the relationship between PF4-H antibodies and hemodialysis vascular access thrombosis in a case-control study.


METHODS
Pre-dialysis blood samples were drawn on 419 patients; 107 cases with access thrombosis and 312 controls that never had access thrombosis. All samples were screened for PF4-H antibodies using an ELISA assay (GTI PF4 Enhanced, GTI Diagnostics). All positive and indeterminate samples were then tested using an IgG-specific PF4-H ELISA assay and a platelet serotonin-release assay.


RESULTS
Antibodies to PF4-H were positive in 54 (12.9%) patients using the screening ELISA assay. Nine (2.1%) patients had IgG-specific PF4-H antibodies. None of the patient's had a positive platelet serotonin-release assay. No relationship between hemodialysis access thrombosis and PF4-H antibodies was noted using the screening ELISA assay (unadjusted odds ratio 0.63; 95% CI 0.30-1.30; P = 0.21), the IgG-specific ELISA assay (unadjusted odds ratio 0.83; 95% CI 0.17-4.06; P = 0.82) or indeterminate platelet serotonin-release assay results (unadjusted odds ratio 0.97;95% CI 0.10-9.44;P = 0.98).


CONCLUSIONS
Hemodialysis with repeated exposure to unfractionated heparin was associated with a moderately elevated prevalence of PF4-H antibodies. However, our results do not support a relationship between PF4-H antibodies and hemodialysis vascular access thrombosis.
Carrier
Marc
M
Thrombosis Program, Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada.
Knoll
Greg A
GA
Kovacs
Michael J
MJ
Moore
Jane C
JC
Fergusson
Dean
D
Rodger
Marc A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000737:chemistry / Q000276:immunology*; D006435:Renal Dialysis / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology
D001323:Autoantibodies; D046911:Macromolecular Substances; D010978:Platelet Factor 4; D006493:Heparin