INTRODUCTION

Hemoglobinopathy detection is often a part of the evaluation of anemia, hemolysis, microcytosis, cyanosis, or erythrocytosis. For this purpose, protein (hemoglobin)-, cellular-, and DNA-based approaches to the detection of variant hemoglobins and thalassemias are available. Diagnostic details can be found in each disease-specific chapter, whereas in the following pages we focus on the available methods and their strengths and weaknesses.

Characterization of mutant hemoglobins and thalassemias described throughout this book takes place in different contexts: large newborn screening laboratories that need to identify positively the most common mutants; general hematology laboratories that most often encounter common hemoglobinopathies and thalassemias; and reference or research laboratories that can detect rare mutant globin genes. Approaches that are necessary in one setting might not be practical in others.

Normal adult blood contains predominantly HbA (α2β2) and small amounts of HbF (α2γ2) and HbA2 (α2δ2). After synthesis, monomeric globin chains form α/non-α dimers that do not dissociate under physiological conditions. In the presence of oxygen, hemoglobin tetramers rapidly dissociate into very low concentrations of dimers that can then form new tetramers. This implies that when more than one α- or non-α-chain is present, the predominant form in the red cell will be the heterotetramer (for example, in red cells of HbSC disease, the dominant species will be α2βSβC, and α2βSγ heterotetramers form when HbS is present with high levels of HbF (Fig. 28.1).