title: Polymorphism of the Fcγ Receptor II as a Possible Predisposing Factor for Heparin-Induced Thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) represents a serious complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. However, only a portion of the antibodies have the ability to activate platelets, and these can be identified by a platelet aggregation test (functional testing). However, this expression has been detected to have a molecular cause, which is a mutation of FcγRIIa. The FcγRIIa receptor is responsible for the activation of platelets by antibodies in HIT.
  
  
  METHODS
  To determine HIT, impedance aggregometry using the Multiplate analyzer (MEA) as heparin-induced aggregation technique and the Technozym HIT IgG ELISA test were used. The MEA method uses sensitization of donor platelets with patient plasma in the presence of heparin at a concentration of 0.5 IU/mL. The results were compared with the ELISA test. Mutation of FcγRHa was assessed using the asymmetric real-time PCR method that is based on the reaction with two hybridization probes and melting curve analysis.
  
  
  RESULTS
  Examined were 100 patients at a clinically intermediate and higher risk of HIT according to the 4T's score. All samples were examined by the ELISA test and MEA, with positive samples being further confirmed by high-concentration heparin. In the group of patients, 10.0% were positive by MEA as compared with 4% determined by ELISA. The results of genetic analysis of FcγRIIa did not provide statistically significant differences between positive patients found by the functional test as well as the ELISA test and seronegative patients.
  
  
  CONCLUSIONS
  The genetic mutation FcγRIIa is a predisposing factor for manifestation of HIT in the form of thrombocytopenia, but the process of seroconversion apparently needs another inducing factor. Therefore, the examination of mutations can be classified as predisposing factors rather than to confirm the diagnosis of HIT.
authors.forename: Ludek
authors.initials: L
authors.lastname: Slavik
authors.forename: Gabriela
authors.initials: G
authors.lastname: Svobodova
authors.forename: Jana
authors.initials: J
authors.lastname: Ulehlova
authors.forename: Vera
authors.initials: V
authors.lastname: Krcova
authors.forename: Antonin
authors.initials: A
authors.lastname: Hlusi
authors.forename: Jana
authors.initials: J
authors.lastname: Prochazkova
authors.forename: Martin
authors.initials: M
authors.lastname: Hutyra
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology
chemical_list: D000925:Anticoagulants; C445323:FCGR2A protein, human; D017452:Receptors, IgG; D006493:Heparin