Serum Antibodies to the Heparin/Platelet Factor 4 Complex Are an Independent Predictor of Thrombotic Complications Following Pediatric Fontan Surgery

Abstract

Antibodies to the heparin/platelet factor 4 complex (heparin/PF4) are linked to the pathogenesis of heparin-induced thrombocytopenia (HIT) and to the thrombotic complications. We investigated thrombotic events during early follow-up in a pediatric cardiac surgical population to ascertain whether there is a relation between heparin/PF4 antibody concentration and post-surgical thrombotic complications. One hundred and five consecutive pediatric patients treated by Fontan surgery were studied. The presence of serum heparin/PF4 immunoglobulins IgG, IgA, and IgM (collectively termed HIT antibodies) were measured in preoperative and postoperative blood samples by enzyme-linked immunosorbent assay. On day six after Fontan surgery, HIT-related thromboses was identified in total of 11 patients (10.5%). HIT antibodies were detected in 34 of 105 patients (32.4%). The post-surgical nadir platelet count was significantly lower in patients who developed antibodies ( p < 0.001). We found the odds ratio (OR) for this composite endpoint was 4.06 ( p < 0.001). Seropositive status for heparin/PF4 antibodies was an independent predictor of thrombotic events (OR 2.28; p < 0.001). Quintile analysis revealed that the median nadir platelet value was significantly lower in patients with higher HIT antibody titers. Patients in the highest quintile of HIT antibody titer all experienced thrombotic events, while only two thrombotic events occurred in patients in the lowest quintile ( p < 0.001). Heparin-induced thrombocytopenia is a rare occurrence in pediatric cardiac surgical patients. Patients who develop antibodies to the heparin/PF4 complex have a significantly higher rate of postoperative thrombotic events than patients who lack these antibodies. Within the seropositive group, the risk of developing thrombosis increased with the plasma antibody concentration.