title: Prevalence and clinical implications of anti-PF4/heparin antibodies in intensive care patients: a prospective observational study.
abstract: Data on the frequency of anti-platelet factor 4/heparin (PF4/H) antibodies and their association with outcomes in intensive care unit (ICU) patients are sparse. In this prospective, observational study we screened 320 consecutive surgical/medical ICU patients for anti-PF4/H antibodies by enzyme-immunoassay (EIA) for immunoglobulin (Ig)G/A/M separately and heparin-induced platelet activation assay (HIPA) at ICU admission (=baseline), day 6, and day 10. HIPA-positive patients were additionally tested by serotonin-release assay (SRA). Patients tested positive by day 10: for anti-PF4/H-IgG = 17.2 % and for anti-PF4/H-IgM = 42.1 %. Within the first 10 ICU days, platelet counts decreased to <100 Gpt/L in 27.8 % patients. However, only seven patients (2.2 %) experienced a drop in the platelet count ≥50 % beginning after the fourth ICU day. These included the only two patients (0.6 %; 95 % confidence interval 0.08-2.2 %) with heparin-induced thrombocytopenia (HIT). Only strong reactions in the HIPA were reproducible by SRA. This study confirms that testing for anti-PF4/H IgG antibodies should be restricted to ICU-patients who develop a platelet count decrease of >50 % that begins after day four of heparin treatment (which may have started before ICU admission). Among patients testing positive by IgG-specific EIA a functional platelet activation assay should be performed (regarding only strong reactions as positive).
authors.affiliation: Department of Anaesthesiology and Intensive Care, University Medicine Greifswald, Sauerbruchstr., 17475, Greifswald, Germany, sselleng@uni-greifswald.de.
authors.forename: Sixten
authors.initials: S
authors.lastname: Selleng
authors.forename: Kathleen
authors.initials: K
authors.lastname: Selleng
authors.forename: Sigrun
authors.initials: S
authors.lastname: Friesecke
authors.forename: Matthias
authors.initials: M
authors.lastname: Gründling
authors.forename: Sven-Olaf
authors.initials: SO
authors.lastname: Kuhn
authors.forename: Ricarda
authors.initials: R
authors.lastname: Raschke
authors.forename: Olivia J
authors.initials: OJ
authors.lastname: Heidecke
authors.forename: Carsten
authors.initials: C
authors.lastname: Hinz
authors.forename: Gregor
authors.initials: G
authors.lastname: Hron
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007362:Intensive Care Units; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000097:blood / Q000276:immunology; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology / Q000276:immunology / Q000473:pathology
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D006493:Heparin; D010978:Platelet Factor 4