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Keywords:

  • quantitative anti-PF4/heparin antibody;
  • heparin-induced platelet activation assay;
  • heparin-induced thrombocytopenia;
  • heparin-induced thrombosis

Abstract

Background:  Heparin-induced thrombocytopenia (HIT) is a prothrombotic immune-mediated adverse drug reaction. Antigen and platelet activation assays are used for detection of antibodies. Quantitative results from platelet factor 4 (PF4)-dependent immunoassays may lead to inter-laboratory standardization of measurements.

Objectives:  The aim was to modify a PF4-dependent immunoassay to measure PF4/heparin antibodies quantitatively.

Methods:  Over five consecutive years, 1070 samples from thrombocytopenic, heparin-treated patients were analyzed by a PF4/heparin ELISA and the heparin-induced platelet activation assay (HIPA). Results of ELISA assay were expressed as arbitrary units per liter (AU/L).

Results:  Precision of ELISA at the concentration of 50 AU/L was 3.6%. Of 1070 samples, 117 were positive for antibodies by ELISA and/or HIPA assay. The higher the antibody concentration was, the higher was the proportion of HIPA positive cases (>140 AU/L, 100%, n = 26; 100–140 AU/L, 55%, n = 20; 50–99 AU/L, 38%, n = 29; 30–49 AU/L, 17%, n = 36).

Conclusions:  The measurement of anti-PF4/heparin antibody concentration is a new parameter that may improve the diagnosis of HIT. All samples with extremely strong antibody concentration were positive also by HIPA. For accuracy, antibody concentrations must be in the linear range of the assay and an international standard is needed.