Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis

Abstract

Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20-50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The FcgammaRIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the FcgammaRIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism FcgammaRIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the FcgammaRIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the FcgammaRIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the FcgammaRIIa polymorphism did not statistically differ between HIT type II and normal controls.

Antibodies to Platelet Factor 4–Heparin Complex and Outcome in Hemodialysis Patients with Diabetes

“…In line with previous work (7,25), we identified increased PF4-H-ABs in a high percentage (18.7%) of patients. We underline that the study took place before the problems with chondroitin sulfate, but the actual purity of heparin that was used from 1998 through 2002 remains unclear.…”

Frequency of Anti-Heparin-PF4 Complex Antibodies (HIT Antibodies) in Uremic Patients on Chronic Intermittent Hemodialysis

“…This figure was consistent with the report of 2 patients (2.8%) having HIT antibodies among 170 patients with chronic dialysis [9] . Seven of 207 (17.9%) chronic dialysis patients were found to be positive for HIT antibodies, and there was no correlation between platelet counts and titers of HIT antibodies [10] . In chronic dialysis patients, complications such as fistula and graft thrombosis, congestive heart failure and ischemic heart disease can be life threatening.…”

Platelet dysfunction in Uremia

“…PF4/H-Antikörper können jedoch an aktivierte Thrombozyten trotz Vorbehandlung mit einem monoklonalem Antikörper gegen den FcγRII-Rezeptor binden [217,218]. Untersuchungen zum Polymorphismus des FcγRIIa-Rezeptors haben keine Unterschiede zwischen HIT-II-Patienten und Kontrollen ergeben [219]. Durch die Heparinbindung an PF4 wird eine Konformationsänderung des Moleküls induziert.…”