Original Article

Ann Lab Med 2022; 42(2): 169-177

Published online March 1, 2022

Copyright © Korean Society for Laboratory Medicine.

Impact of Individualized Hemolysis Management Based on Biological Variation Cut-offs in a Clinical Laboratory

Fernando Marques-Garcia , Ph.D., David Hansoe Heredero Jung , M.D., and Sandra Elena Pérez, B.D.

Department of Clinical Biochemistry, University Hospital of Salamanca, Salamanca, Spain

Correspondence to: Fernando Marques-Garcia, Ph.D.
Department of Clinical Biochemistry, University Hospital of Salamanca, Salamanca, Spain
Tel: +34-923-291100

Received: February 7, 2021; Revised: June 11, 2021; Accepted: September 16, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Hemolysis is the most common type of preanalytical interference. Cut-offs based on the hemolysis index level can be established using different approaches. The Working Group for Preanalytical Phase of the European Federation of Laboratory Medicine has developed a protocol for hemolysis management based on cut-offs estimated from biological variation (BV) and the use of interpretative comments. We developed and assessed the implementation of the protocol in our laboratory.
Methods: Hemolysates from whole blood were prepared following the Meites method, and pooled serum samples with known Hb concentrations were prepared. For each analyte (42 ), interferograms were generated and used to establish cut-offs: desirable analytical quality specification and reference change value. This protocol was assessed, both pre- and post-implementation, according to expert rules in the Laboratory Information System.
Results: Among the analytes evaluated, we selected those that showed the highest degree of hemolysis interference: lactate dehydrogenase (LDH), aspartate aminotransferase, direct bilirubin, potassium, and folic acid. The cut-offs for LDH and direct bilirubin were the lowest. Only 28.16% of all LDH values were adequately reported in the pre-implantation retrospective study, but this percentage improved in the post-implementation stage.
Conclusions: The development and implementation of a harmonized protocol for hemolysis management based on BV cut-offs and result reporting significantly improve hemolysis detection and lead to a decrease in the number of hemolyzed samples over time.

Keywords: Hemolysis, Interference, Biological variation, Cut-off, Harmonization