Differential Prevalence of Anti‐Heparin PF4 Immunoglobulin Subtypes in Patients Treated with Reviparin, Enoxaparin, and Certoparin. Implications in HIT Pathogenesis.

Abstract

Heparin and low molecular weight heparin (LMWHs) represent complex mixtures of sulfomucopolysaccharides with structural and functional heterogeneity. Therefore, there interactions with endogenous binding proteins such as platelet factor 4 (PF4) differ leading to differential neutralization and immunogenic responses. In order to demonstrate the difference in immunogenic responses in plasma samples from patients treated in three different clinical trials, namely ECHOS (Reviparin, 4200 anti‐Xa U/o.d., s.c. for 11–14 days) for post‐orthopedic prophylaxis; OCENOX (enoxaparin, 1.0 mg/kg s.c. bid for up to 3 months) for treatment of deep vein thrombosis in cancer patients and PARAT (Certoparin, 1mg/kg s.c.,o.d. for up to 3 months) for post PTCA restenosis were retrospectively analyzed for the presence of anti‐heparin – PF4 antibodies and there subtypes using an ELISA method (GTI, Brookfield, WI). The antibody titers and subtypes were compared in samples collected at 10–14 days. Of the 100 samples analyzed in each of these groups, the prevalence of ELISA positive antibodies differed, Reviparin (12.5%), Enoxaparin (15.2%) and Certoparin (18.1%). None of these sera produced 14C serotonin release. The subtyping of these antibodies in terms of IgG, IgA and IgM, also exhibited different profiles with predominant IgA and IgM subtypes. Certoparin exhibited relatively higher IgG subtypes. These studies demonstrated that the immunogenic potential of different LMWHs vary widely in terms of the antibody titer and subtypes.