title: Delta-He, Ret-He and a New Diagnostic Plot for Differential Diagnosis and Therapy Monitoring of Patients Suffering from Various Disease-Specific Types of Anemia.
abstract: BACKGROUND
  The present study was aimed to prove the usefulness of a new diagnostic plot (Hema-Plot), illustrating the relationship between the hemoglobin content of reticulocytes (Ret-He) as a marker of functional iron deficiency and the difference between the reticulocyte and erythrocyte hemoglobin content (Delta-He) as a marker of an impaired hemoglobinization of newly formed reticulocytes occurring during inflammatory processes, to differentiate between various disease-specific types of anemia.
  
  
  METHODS
  A complete blood and reticulocyte count was performed on routine EDTA blood samples from 345 patients with and without various disease-specific types of anemia using the Sysmex XN-9000 hematology analyzer: blood healthy newborns (n = 23), blood healthy adults (n = 31), patients suffering from anemia of chronic disease (ACD) due to diverse oncological, chronic inflammatory, or autoimmune diseases (total n = 138) with (n = 65) and without therapy (n = 73), patients with thalassemia and/or hemoglobinopathy (n = 18), patients with iron deficiency anemia (IDA) (n = 35), patients with a combination of ACD and IDA (n = 17), as well as patients suffering from sepsis (total n = 83) with (n = 32) and without therapy (n = 51). The results for Ret-He, Delta-He, and C-reactive protein (CRP) were statistically compared (Mann-Whitney U Test) between the particular patient groups and the diagnostic plots were drawn.
  
  
  RESULTS
  Delta-Hemoglobin showed a statistically significant difference between blood healthy newborns and blood healthy adults (p ≤ 0.05), while Ret-He and C-reactive protein did not. In addition, of all three biomarkers only Delta-He showed a statistically significant difference (p ≤ 0.05) between the ACD/IDA and IDA cohort. Delta-He, Ret-He, and CRP showed a statistically significant difference between patient cohorts with and without therapy suffering from ACD, ACD/IDA, and sepsis before and after medical therapy (p ≤ 0.05). The Hema-Plot illustrated the dynamic character of Ret-He and Delta-He, notably in inflammation-based types of anemia like ACD or ACD/ IDA.
  
  
  CONCLUSIONS
  Delta-He is a new biomarker clearly distinguishing between inflammation-based types of anemia before and after medical therapy, as well as between ACD/IDA and IDA. The new Hema-Plot is a helpful tool for differential diagnosis and disease-monitoring in various types of disease-specific anemia, especially in ACD and ACD/IDA. The Hema-Plot can be used to identify non-adherent patients or an insufficient therapy.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weimann
authors.forename: Malte
authors.initials: M
authors.lastname: Cremer
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernáiz-Driever
authors.forename: Mathias
authors.initials: M
authors.lastname: Zimmermann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000175:diagnosis* / Q000628:therapy; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012156:Reticulocytes / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D002097:C-Reactive Protein