title: IgG classification of anti-PF4/heparin antibodies to identify patients with heparin-induced thrombocytopenia during mechanical circulatory support.
abstract: Commercial immunoassays frequently detect anti-PF4/heparin antibodies during mechanical circulatory support (MCS), but only a small minority of patients develops heparin-induced thrombocytopenia (HIT). Whereas platelet functional tests can distinguish between platelet-activating and non-platelet-activating antibodies, commercial PF4-dependent immunoassays do not. Between 2003 and 2004, 113 patients were placed on MCS. Blood samples were obtained on postimplant day 5-7 for analyses by antibody assays and the functional heparin-induced platelet activation (HIPA) assay. Three distinct groups of patient sera were identified: platelet-activating anti-PF4/heparin antibodies (n = 10), non-platelet-activating anti-PF4/heparin antibodies (n = 53), and anti-PF4/heparin antibody negative (n = 50). Patients with platelet-activating antibodies had the highest risk for thromboembolic events (P < 0.005), whereas those with non-platelet-activating antibodies did not differ from antibody negative patients (P = 0.369). The enzyme-immunoassay and column agglutination assays, which cover all immunoglobulin classes, demonstrated adequate sensitivity and negative predictive value; yet, both lacked specificity with respect to the platelet-activating antibodies. If all antibody positive patients were further classified by an IgG-specific anti-PF4/heparin enzyme-immuno assay, specificity for platelet-activating antibodies increased. Whereas IgG-specific optical density (OD) values below 1.0 were likely for non-platelet-activating anti-PF4/heparin antibodies, higher values were progressively predictive for pathogenic platelet activation. The probability of the development of clinical HIT also increased steeply. In conclusion, platelet-activating anti-PF4/heparin antibodies are relatively common (about 9%) in patients on MCS and are associated with significantly higher thrombotic event rates. Low IgG-specific OD values (< 1.0) in the enzyme-immunoassay indicate low likelihood for the presence of platelet-activating antibodies. These results justify further validation so that anticoagulation during MCS becomes safer and adequate.
authors.affiliation: Thoracic and Cardiovascular Surgery, Heart Center North Rhine Westphalia, Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schenk
authors.forename: A
authors.initials: A
authors.lastname: El-Banayosy
authors.forename: M
authors.initials: M
authors.lastname: Morshuis
authors.forename: L
authors.initials: L
authors.lastname: Arusoglu
authors.forename: P
authors.initials: P
authors.lastname: Eichler
authors.forename: N
authors.initials: N
authors.lastname: Lubenow
authors.forename: G
authors.initials: G
authors.lastname: Tenderich
authors.forename: R
authors.initials: R
authors.lastname: Koerfer
authors.forename: A
authors.initials: A
authors.lastname: Greinacher
authors.forename: W
authors.initials: W
authors.lastname: Prohaska
mesh_terms: D001243:Assisted Circulation / Q000009:adverse effects*; D001323:Autoantibodies / Q000032:analysis* / Q000145:classification; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods / Q000592:standards; D007074:Immunoglobulin G; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000276:immunology; D010978:Platelet Factor 4 / Q000276:immunology*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology; D013923:Thromboembolism / Q000209:etiology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D010978:Platelet Factor 4; D006493:Heparin