title: High sensitivity and specificity of a new functional flow cytometry assay for clinically significant heparin-induced thrombocytopenia antibodies.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a life-threatening condition, in which the anticoagulant heparin, platelet factor 4 (PF4), and platelet-activating antibodies form complexes with prothrombotic properties. Laboratory tests to support clinical diagnosis are subdivided into functional, platelet activation assays, which lack standardization, or immunological assays, which have moderate specificity toward HIT. In this study, clinical performance of HITAlert, a novel in vitro diagnostic (IVD) registered platelet activation assay, was tested in a large cohort of HIT-suspected patients and compared with immunological assays.
  
  
  METHODS
  From 346 HIT-suspected patients (single center), clinical data including 4T pretest probability results, citrated platelet-poor plasmas, and sera were collected, allowing direct comparison of clinical observations with HITAlert results. HITAlert performance was compared with PF4 IgG ELISA (246 patients, three centers) and PF4 PaGIA (298 patients, single center).
  
  
  RESULTS
  HITAlert showed high sensitivity (88.2%) and specificity (99.1%) when compared with clinical diagnosis. Agreement of HITAlert with PF4 ELISA- and PF4 PaGIA-positive patients is low (52.7 and 23.2%, respectively), while agreement with PF4 IgG ELISA- and PF4 PaGIA-negative patients is very high (98.1 and 99.1%, respectively).
  
  
  CONCLUSIONS
  HITAlert performance is excellent when compared with clinical HIT diagnosis, making it a suitable assay for rapid testing of platelet activation due to anticoagulant therapy.
authors: Institute for Clinical Transfusion Medicine and Children Hospital (WE), Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany.
authors: H S
authors: HS
authors: Garritsen
authors: M
authors: M
authors: Probst-Kepper
authors: N
authors: N
authors: Legath
authors: W
authors: W
authors: Eberl
authors: S
authors: S
authors: Samaniego
authors: J
authors: J
authors: Woudenberg
authors: J H N
authors: JH
authors: Schuitemaker
authors: H
authors: H
authors: Kroll
authors: D A
authors: DA
authors: Gurney
authors: G W
authors: GW
authors: Moore
authors: J L
authors: JL
authors: Zehnder
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D005434:Flow Cytometry / Q000379:methods; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G; D010978:Platelet Factor 4; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis*
chemical_list: D000925:Anticoagulants; D007074:Immunoglobulin G; D010978:Platelet Factor 4; D006493:Heparin
keywords: Heparin-induced thrombocytopenia; functional