title: Platelet microparticle generation assay: a valuable test for immune heparin-induced thrombocytopenia diagnosis.
abstract: BACKGROUND
  Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is essential to improve clinical outcome but remains challenging. The release of platelet microparticles (PMPs) is considered of major pathophysiological significance.
  
  
  OBJECTIVE
  The aim of this study was to evaluate performances of PMP generation assay (PMPGA) compared to clinical outcome to diagnose HIT. The second objective was to compare PMPGA with performances of (14)C-serotonin release assay (SRA) on the same series of patients.
  
  
  METHODS
  Sera of 53 HIT-suspected patients were retrospectively incubated with citrated-whole blood from healthy donors with 1IU and 500IU/ml of unfractionated heparin (UH). PMPGA was performed using FACSAria® flow cytometer. The clinical diagnosis was established by two blinded independent investigators analysing in a standardized manner the patient's medical records. Performances of PMPGA and SRA (n=53) were evaluated using ROC curve analysis with clinical outcome as reference.
  
  
  RESULTS
  In positive HIT patients, PMPs expressing phosphatidylserine are generated with low UH concentration whereas PMP rate decreases significantly in presence of high UH concentration. Using clinical outcome as reference, sensitivity and specificity of PMPGA reached 88.9% (95% CI: 50.7-99.4) and 100.0% (95% CI: 90.0-100.0). Sensitivity and specificity of (14)C-SRA were 88.9% (95% CI: 50.7-99.4) and 95.5% (95% CI: 83.3-99.2).
  
  
  CONCLUSIONS
  PMPGA is a rapid and reliable assay for HIT diagnosis. PMPGA showed good correlation with (14)C-SRA performances and predominately with clinical outcome.
authors.affiliation: Hematology Laboratory- Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium; Department of Pharmacy- Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium; Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium. Electronic address: mullierfrancois@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Mullier
authors.affiliation: Department of Pharmacy- Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Minet
authors.affiliation: Hematology Laboratory- Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Bailly
authors.affiliation: Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium; Hematology Department- Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Devalet
authors.affiliation: Department of Pharmacy- Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium; Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Douxfils
authors.affiliation: Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium; Hematology Department- Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Chatelain
authors.affiliation: Hematology Department, Hôpital Tenon, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Elalamy
authors.affiliation: Department of Pharmacy- Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium; Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium.
authors.forename: J M
authors.initials: JM
authors.lastname: Dogné
authors.affiliation: Hematology Laboratory- Namur Research Institute for LIfe Sciences (NARILIS), CHU Dinant-Godinne UCL Namur, Yvoir, Belgium; Namur Thrombosis and Hemostasis Center (NTHC), Namur, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Chatelain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001792:Blood Platelets / Q000473:pathology / Q000648:ultrastructure*; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006493:Heparin
keywords: heparin-induced thrombocytopenia; microparticles; platelets; thrombosis