Association of anti-heparin platelet factor 4 antibody levels and thrombosis in pediatric intensive care patients without thrombocytopenia.

Anti-heparin platelet factor 4 (anti-HPF4) antibodies have been demonstrated to play a pathogenetic role in the development of heparin-induced thrombocytopenia. In adults, the presence of anti-HPF4 antibodies without thrombocytopenia has been reported not to confer a thrombotic risk. To investigate whether this also holds true for children, we performed a case-control study in heparin-exposed patients from a pediatric intensive care unit. During the 30-month study period, 612 patients received heparin for at least 5 days. Of these, 10 patients developed thrombosis without thrombocytopenia and constituted the study group. These patients were compared with 19 matched control patients with neither thrombosis nor thrombocytopenia. Anti-HPF4 antibody levels were measured using an enzyme-linked immunosorbent assay (Asserachrom HPF4). All thrombosis patients and controls had lower anti-HPF4 antibody levels than the cut-off level recommended by the manufacturer for adults. However, median anti-HPF4 antibody levels were significantly higher in the thrombosis patients [51% of the manufacturer's cut-off; interquartile range (IQR), 47-53%] than in the control group (23%; IQR, 9-36%) (P = 0.004). At an anti-HPF4 cut-off level of 45%, the odds ratio for a thrombotic event amounted to 34 (95% confidence interval, 4.4-261.8), indicating an association between anti-HPF4 antibody levels and thrombosis despite the absence of thrombocytopenia. A role of anti-HPF4 antibodies in the development of catheter-related thrombosis is suggested. Copyright 2003 Lippincott Williams & Wilkins