Screening tools for hereditary hemolytic anemia: new concepts and strategies

Abstract

Introduction

Hereditary hemolytic anemias are a group of rare and heterogeneous disorders due to abnormalities in structure, metabolism, and transport functions of erythrocytes; they may overlap in clinical and hematological features making differential diagnosis difficult, particularly in mild and atypical forms.

Areas covered

In the present review, the main tools currently adopted in routine hematologic investigation for the diagnosis of hereditary hemolytic anemias are described, together with the new diagnostic approaches that are being to be developed in the next future. Available recommendations in this field together with a systematic review through MEDLINE, EMBASE, and PubMED for publications in English from 2000 to 2020 in regards to diagnostic aspects of hereditary hemolytic anemias have been considered.

Expert opinion

The recent development of specific molecules and treatments for hereditary hemolytic anemias and the increased interest in translational research raised the attention on differential diagnosis and the demand for novel diagnostic assays and devices. Automatic blood cell analyzers, omic-approaches including NGS technologies, and development of new automated tools based on artificial neural networks definitely represent the future strategies in this field.

KEYWORDS:

• Hereditary hemolytic anemia
• screening tools
• diagnosis
• red blood cells
• next generation sequencing
• functional tests

Article highlights box

• Diagnosis of hereditary hemolytic anemia may be difficult particularly in mild and atypical forms, due to clinical and hematologic overlaps between the different diseases.

• The diagnostic workflow is based on a panel of laboratory tests including different levels of investigation, sometimes available only in specialized Centers.

• None of the screening tests when used alone can reach a definitive diagnosis in 100% of cases, and some patients remain undiagnosed also after extensive and complete investigations.

• EMA binding test and ektacytometry Osmoscan are tools used for screening of membrane disorders and when combined have the best performance in detecting HS.

• Molecular testing permits to reach a definitve diagnosis and its use is increasing thanks to the development of NGS techniques.

• The diagnostic success rate of NGS is higher when is used in combination with conventional methods, together with a detailed phenotyping and clinical classification of the patients. Functional tests are often needed to confirm the pathogenicity of the detected variants.

• New approaches are currently being developed to automatize the diagnostic iter and to expand functional tests.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by research funding from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, grant number RC2020, 175/05.