Determination of heparin–platelet factor 4–IgG antibodies improves diagnosis of heparin‐induced thrombocytopenia

Abstract

Only a few patients with heparin‐induced antibodies develop heparin‐induced thrombocytopenia (HIT). In this study, we investigated whether different immunglobulin classes can be used to differentiate between antibody‐positive patients with and without HIT. Four different patient populations were investigated: 32 patients with the immune type of HIT with thromboembolic complications, 13 patients with HIT without thromboembolism, 24 patients with heparin–platelet factor 4 (PF4) antibodies without clinical symptoms of HIT, and 20 heparin‐treated patients with thrombocytopenia caused by other reasons. In all patients the immunglobulin mixture of IgG, IgM and IgA, and the single immunglobulin classes of heparin–PF4 antibodies, were investigated. No significant differences between HIT patients with thromboembolic complications and patients with isolated HIT were found concerning the different immunglobulin classes. Antibody‐positive patients with HIT had significantly higher levels of IgG antibodies than those without HIT (P < 0·05), while they did not differ concerning IgM and IgA antibodies. By determining IgG antibodies, the specificity of the enzyme‐linked immunosorbent assay (ELISA) system was increased without loss of sensitivity. Heparin–PF4–IgG antibodies can identify patients at risk of developing life‐threatening HIT. Future ELISAs should only include this immunglobulin class, as the determination of the antibody mixture may lead to overestimation of HIT.

Heparin‐induced thrombocytopenia and thrombosis

“…In that respect, it is both highly sensitive [37] and specific, because positive reactions are extremely rare in patients not exposed to heparin [30]. In various studies, 2-13% of patients thought to have HIT on clinical grounds were antibody-negative [40][41][42][43], but it is impossible to know how many of them may have had some other cause for their thrombocytopenia. In our experience, it is extremely rare for patients with ''typical'' HIT, especially those with associated thromboses, not to test positive in the ELISA.…”

“…Although antibodies of the IgM and IgA classes are common in HIT [44,70], they are incapable of activating platelets through their Fc receptors, and it has been suggested that only IgG antibodies are ''clinically significant'' [6,42]. However, available commercial kits are designed to detect antibodies of all Ig classes, in part because of early reports describing patients with HIT (some with thrombosis) whose antibodies were exclusively IgM [70,71].…”

Anti–platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin

“…This end point was chosen because IgG class antibodies are more likely to cause HIT than antibodies of other classes. 21 All other end points were secondary end points.…”

“…20 Further, clinical HIT is most likely to be caused by antibodies of IgG class. 21 Danaparoid sodium was obtained from Organon (Toronto, ON, Canada).…”

Heparin‐induced thrombocytopenia: Current status and diagnostic challenges

“…To aid in the interpretation of a positive EIA, the clinician should consider the clinical scenario (i.e., the pretest probability based on the ''4Ts'') and the absolute value of the OD. Several studies have documented that high OD values (corresponding to high titers of HIT antibodies) are associated with a higher likelihood of a positive HIPA, a higher ''4Ts'' score (clinical HIT), and a higher probability of thrombotic complications [31][32][33][34][35].…”