Korean clinical practice guidelines for the diagnosis of hereditary hemolytic anemia

Abstract

Although the prevalence of hereditary hemolytic anemia (HHA) is relatively low in Korea, it has been gradually increasing in recent decades due to increment in the proportions of hemoglobinopathies from immigrants of South East Asia, raising awareness of the disease among clinicians, and advances in diagnostic technology. As such, the red blood cell (RBC) Disorder Working Party (WP), previously called HHA WP, of the Korean Society of Hematology (KSH) developed the Korean Standard Operating Procedures (SOPs) for the diagnosis of HHA in 2007. These SOPs have been continuously revised and updated following advances in diagnostic technology [e.g., flow cytometric osmotic fragility test (FOFT) and eosin-5-maleimide (EMA) binding test], current methods for membrane protein or enzyme analysis [e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC)], and molecular genetic tests using next-generation sequencing (NGS). However, the diagnosis and treatment of HHA remain challenging as they require considerable experience and understanding of the disease. Therefore, in this new Korean Clinical Practice Guidelines for the Diagnosis of HHA, on behalf of the RBC Disorder WP of KSH, updated guidelines to approach patients suspected of HHA are summarized. NGS is proposed to perform prior to membrane protein or enzyme analysis by LC-MS/MS, UPLC-MS/MS or HPLC techniques due to the availability of gene testing in more laboratories in Korea. We hope that this guideline will be helpful for clinicians in making diagnostic decisions for patients with HHA in Korea.

Molecular diagnosis of hereditary hemolytic anemias: Recent updates

“…For example, according to the Korean clinical practice guidelines for the diagnosis of HHA, genetic testing is reserved for the cases where (1) the routine studies have failed or achieved inconclusive results to identify the causative mechanism; (2) RBC transfusions have been recently administered to avoid the confounding of biochemical and other testing; and/or (3) the patient is a newborn. 30 Alternatively to the traditional testing sequence, some institutions swap the last two steps, with molecular testing being performed before the specialized testing. In that case, specialized testing is sometimes omitted.…”

“…In settings where molecular testing is not readily available or not cost‐effective, the first two steps may suffice to achieve a clinically relevant final diagnosis. For example, according to the Korean clinical practice guidelines for the diagnosis of HHA, genetic testing is reserved for the cases where (1) the routine studies have failed or achieved inconclusive results to identify the causative mechanism; (2) RBC transfusions have been recently administered to avoid the confounding of biochemical and other testing; and/or (3) the patient is a newborn 30 …”

Literature review on genotype–phenotype correlation in patients with hereditary spherocytosis

“…EMABT combined with OFT and AGLT is suggested by the International Council for Standardization in Hematology (ICSH) to screen for patients with HS 10 . Furthermore, OFT and EMABT by flow cytometry have shown promising value in the diagnosis of HS, 11 which is recommended in Korean clinical practice guidelines 12 . In addition, mass spectrometry‐based techniques are proposed preferentially to quantify erythrocyte membrane proteins rather than sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) 12 …”

“…10 Furthermore, OFT and EMABT by flow cytometry have shown promising value in the diagnosis of HS, 11 which is recommended in Korean clinical practice guidelines. 12 In addition, mass spectrometry-based techniques are proposed preferentially to quantify erythrocyte membrane proteins rather than sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 12 The standardization of laboratory tests such as EMABT and SDS-PAGE is difficult due to the diversity in healthy controls.…”

“…12 In addition, mass spectrometry-based techniques are proposed preferentially to quantify erythrocyte membrane proteins rather than sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 12 The standardization of laboratory tests such as EMABT and SDS-PAGE is difficult due to the diversity in healthy controls. 13,14 Moreover, multiple transfusions could result in unreliability of biochemical testing.…”