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.
Risch
Lorenz
L
Department of Laboratory Medicine, Kantonsspital, Aarau, Zurich.
Fischer
Joachim E
JE
Schmugge
Markus
M
Huber
Andreas R
AR
D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002404:Catheterization / Q000009:adverse effects; D003422:Critical Care; D006493:Heparin / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology*; D013921:Thrombocytopenia; D013927:Thrombosis / Q000097:blood / Q000209:etiology*
D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin