title: Laboratory parameters provided by Advia 2120 analyser identify structural haemoglobinopathy carriers and discriminate between Hb S trait and Hb C trait.
abstract: BACKGROUND
  Haemoglobinopathies have spread owing to human migration, and the number of people needing diagnosis and management of these conditions is increasing. Clinicians need to accurately identify carriers and provide adequate genetic counselling in order to prevent the occurrence of homozygous or compound heterozygous offspring.
  
  
  OBJECTIVE
  To identify red blood cell (RBC) laboratory parameters that discriminate between structural haemoglobinopathy carriers and healthy subjects, and to compare RBC laboratory indices between HbAS and HbAC individuals.
  
  
  METHODS
  Samples of 500 variant Hb carriers (355 HbAS, 104 HbAC, 19 HbAD, 7 HbAE, 7 HbAO-Arab, 4 α-chain variants and 4 Hb Lepore) and 251 normal controls were run on an Advia 2120 analyser (Siemens). Classic haematological parameters and RBC populations were assessed in all subjects. A multivariable binary logistic regression model was created to predict the probability of a subject carrying any structural haemoglobinopathy. HbAS (n=355, 71%) and HbAC (n=104, 20.8%) subjects were compared.
  
  
  RESULTS
  A clinical prediction rule was developed by assigning one point to each of the most efficient variables: mean corpuscular volume (MCV) <88.4 fL, RBC distribution width >13.4%, percentage of microcytic RBCs (%MICRO) >0.7% and the ratio of microcytic RBCs to hypochromic RBCs >0.8. A score of 0, 1, 2, 3 or 4, resulted in a probability of 9.6%, 36.3%, 66.7%, 85.2% or 98.3%, respectively. Among the most frequent variant Hb, HbAC subjects had lower values of parameters related to cell size (MCV, %MICRO) and higher values of parameters related to haemoglobin concentration (MCHC, %HYPER) than HbAS subjects. Coexistence of α-thalassaemia in both HbAS and HbAC individuals resulted in decreased Hb, MCV, MCH and MCHC.
  
  
  CONCLUSIONS
  Structural haemoglobinopathy should be investigated in subjects belonging to ethnic groups with high prevalence of variant Hb and with a score of 3 or 4. Erythrocytes of HbAC subjects are smaller and denser than those of HbAS subjects.
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain Laboratorio Central de la Comunidad de Madrid, Madrid, Spain Programa de Doctorado de Investigación en Ciencias Médico-Quirúrgicas, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Velasco-Rodríguez
authors.affiliation: Laboratorio Central de la Comunidad de Madrid, Madrid, Spain.
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Alonso-Domínguez
authors.affiliation: Laboratorio Central de la Comunidad de Madrid, Madrid, Spain Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Fernando-Ataúlfo
authors.initials: FA
authors.lastname: González-Fernández
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Muriel
authors.affiliation: Laboratorio Central de la Comunidad de Madrid, Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Abalo
authors.affiliation: Laboratorio Central de la Comunidad de Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sopeña
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain Laboratorio Central de la Comunidad de Madrid, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Villarrubia
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ropero
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: María Paz
authors.initials: MP
authors.lastname: Plaza
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Tenorio
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Jiménez-Martín
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Moreno
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez-Nieto
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: de la Fuente-Gonzalo
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Fernández-Escribano
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: López-Jiménez
authors.affiliation: Laboratorio Central de la Comunidad de Madrid, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cava
mesh_terms: D016022:Case-Control Studies; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006403:Hematologic Tests / Q000295:instrumentation*; D006444:Hemoglobin C / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D010641:Phenotype; D011786:Quality Control; D012372:ROC Curve; D015203:Reproducibility of Results; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics
chemical_list: D006451:Hemoglobin, Sickle; D006444:Hemoglobin C
keywords: AUTOMATED SCREENING; HAEMATOLOGY; HAEMOGLOBINOPATHY