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Heparin‐induced thrombocytopenia: a prospective study on the incidence, platelet‐activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes
Author(s) -
GREINACHER A.,
JUHL D.,
STROBEL U.,
WESSEL A.,
LUBENOW N.,
SELLENG K.,
EICHLER P.,
WARKENTIN T. E.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02617.x
Subject(s) - heparin , heparin induced thrombocytopenia , antibody , platelet , immunology , platelet factor 4 , immunoassay , antigen , medicine , annexin a5 , immunoglobulin m , immunoglobulin g , annexin , flow cytometry
Summary. Introduction: Platelet‐activating antiplatelet factor 4/heparin (anti‐PF4/heparin) antibodies are the major cause of heparin‐induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme‐immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. Methods: Consecutive patient sera ( n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin‐induced platelet activation (HIPA) test and anti‐PF4/heparin EIA – including individual classes (IgG, IgA, IgM) – with clinical correlations studied. Platelet microparticle and annexin‐V‐binding properties of the sera were also investigated. Results: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA‐positive, and, notably, only one serum was HIPA‐positive/EIA‐negative. Of 185 EIA‐positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA‐positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA‐positive but EIA‐IgG‐negative sera became HIPA‐negative following IgG depletion, suggesting platelet‐activating antibodies against non‐PF4‐dependent antigens. Clinical correlations showed that HIPA‐negative/EIA‐positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin‐V binding. Conclusions: The anti‐PF4/heparin EIA has high (∼99%) sensitivity for HIT. However, only about half of EIA‐positive patients are likely to have HIT. Anti‐PF4/heparin antibodies of IgM/A class and non‐PF4‐dependent antigens have only a minor role in HIT.