title: Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study.
abstract: BACKGROUND
  The diagnostic evaluation of inherited platelet disorders (IPDs) is complicated and time-consuming, resulting in a relevant number of undiagnosed and incorrectly classified patients. In order to evaluate the spectrum of IPDs in individuals with clinical suspicion of these disorders, and to provide a diagnostic tool to centers not having access to specific platelets studies, we established the project "Functional and Molecular Characterization of Patients with Inherited Platelet Disorders" under the scientific sponsorship of the Spanish Society of Thrombosis and Haemostasis.
  
  
  METHODS
  Subjects were patients from a prospective cohort of individuals referred for clinical suspicion of IPDs as well as healthy controls. Functional studies included light transmission aggregation, flow cytometry, and when indicated, Western-blot analysis of platelet glycoproteins, and clot retraction analysis. Genetic analysis was mainly performed by sequencing of coding regions and proximal regulatory regions of the genes of interest.
  
  
  RESULTS
  Of the 70 cases referred for study, we functionally and molecularly characterized 12 patients with Glanzmann Thrombasthenia, 8 patients with Bernard Soulier syndrome, and 8 with other forms of IPDs. Twelve novel mutations were identified among these patients. The systematic study of patients revealed that almost one-third of patients had been previously misdiagnosed.
  
  
  CONCLUSIONS
  Our study provides a global picture of the current limitations and access to the diagnosis of IPDs, identifies and confirms new genetic variants that cause these disorders, and emphasizes the need of creating reference centers that can help health care providers in the recognition of these defects.
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. sanchezguiu.isabel@gmail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sánchez-Guiu
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. anai.anton@carm.es.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Antón
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. josepadillaruizcrh@gmail.com.
authors.forename: José
authors.initials: J
authors.lastname: Padilla
authors.affiliation: Servicio de Hematología y Hemoterapia, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario, Córdoba, Spain. francisco.velasco.sspa@juntadeandalucia.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.affiliation: Servicio Hematología y Hemoterapia, Hospital Universitario Miguel Servet, Zaragoza, Spain. jfluciac@gmail.com.
authors.forename: José F
authors.initials: JF
authors.lastname: Lucia
authors.affiliation: Servicio de Hemoterapia y Hemostasia, Hospital Clínico, Barcelona, Spain. MLOZANO@clinic.ub.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lozano
authors.affiliation: Unidad de Hemostasia y Trombosis, Servicio Hematología y Hemoterapia, Hospital Universitario Politécnico de la Fe, Valencia, Spain. cid_ana@gva.es.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Cid
authors.affiliation: Serviço de Hematologia do Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. teresasevivas@hotmail.com.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sevivas
authors.affiliation: Servicio Hematología y Hemoterapia, Complejo Hospitalario Universitario A Coruña, La Coruña, Spain. MA.Fernanda.Lopez.Fernandez@sergas.es.
authors.forename: María F
authors.initials: MF
authors.lastname: Lopez-Fernandez
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. Vicente.vicente@carm.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Departament Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (C.S.I.C.),CIBER de Enfermedades Raras, Madrid, Spain. cgmanchon@cib.csic.es.
authors.forename: Consuelo
authors.initials: C
authors.lastname: González-Manchón
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. jose.rivera@carm.es.
authors.forename: José
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, 30003, Spain. mllozano@um.es.
authors.forename: María L
authors.initials: ML
authors.lastname: Lozano
mesh_terms: D000293:Adolescent; D000328:Adult; D001791:Blood Platelet Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003299:Cooperative Behavior; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology; D055815:Young Adult