GRAÇA PORTO (PORTO)
ATYPICAL MICROCYTIC ANEMIAS
Centro Hospital Universitário do Porto; i3S, Instituto de Investigação e Inovação em Saúde da
Universadade do Porto.
Microcytic anemias (MA) are presented here as a clinical illustration of the reciprocal
interactions between iron and erythropoiesis. MA have in common the incapacity of
erythroblasts to mature with an appropriate amount of hemoglobin, which can be due to
defects in any of the three components of hemoglobin synthesis: iron, globin or heme.
Historically, the MA are broadly classified as typical or atypical, reflecting their relative
frequencies in the clinical practice. The so called “typical” microcytic anemias are mainly the
common acquired forms of iron deficiency anemia and the anemia of chronic disease, but also
the thalassemias, which represent the most common among all the inherited forms of MA.
The “atypical” microcytic anemias are predominantly iron related disorders. Among these, the
most prevalent is the Iron Refractory Iron Deficiency Anemia (IRIDA), a genetically very
heterogeneous disease, due to defects in TMPRSS6, a major negative regulator of hepcidin
transcription. For the last decade a growing number of studies came to enlarge the clinical
significance and implications of the TMPRSS6 variants. Questions raised by the evidence of
IRIDA caused by combinations of polymorphisms with pathogenic mutations, wider
associations of TMPRSS6 variants with the iron status and erythroid parameters in adult
populations or as modifiers of other iron related disorders, and new reports of partial
response to oral iron therapy, all point to the need for an expert consensus to better define
the clinical application of TMPRSS6 genotyping for diagnosis, for predicting severity and
response to treatment or even to explain susceptibility to iron deficiency in apparently normal
populations.
Regarding the laboratory approach to MA, a particular attention is called for the importance
of looking at the different erythroid and iron related parameters, including the reticulocyte
hemoglobin content, in an integrated way to allow either confirming an “expected”
phenotype or identifying genotype/phenotype discrepancies, which demand for searching
novel, more complex and rare forms of atypical anemias. An example is given with a case
report where the combination of a very rare cell membrane defect with thalassemia was
overlooked for many years during which time the patient developed a severe iron overload.
Further Reading
Aguilar-Martinez P. Classification and Clinical Approach to Atypical Mycrocytic Anemias. In:
Educational Updates in Hematology Book, 25th Congress of the EHA, virtual edition 2020, page 109
De Falco et al. Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency
anemia patients and genotype-phenotype studies. Hum Mutat. 2014, 35:1321-9.
Donker et al. Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron
refractory. Am J Hematol. 2016;91:E482-E490.
Poggiali et al. The role of TMPRSS6 polymorphisms in iron deficiency anemia partially responsive to
oral iron treatment. Am J Hematol. 2015;90:306-9.
SCIENTIFIC PROGRAMME
SESSION I
BONE MARROW
RESPONSE TO VIRAL
INFECTIONS
SESSION II
HAEMATOLOGICAL
RESPONSE TO SARS
COV2 INFECTION
SESSION III
DYSERYTHROPOIESIS IN
CLONAL HAEMOPOIESIS
AND MDS
SESSION IV
ERYTHROPOIESIS
CONTROL
SESSION V
ERYTHROPOIESIS
CONTROL : PHASE 2
SESSION VI
IRON METABOLISM
AND ERYTHROPOIESIS
SESSION VII
INHERITED
DYSERYTHROPOIESIS
SESSION VIII
GENE THERAPY/EDITION
SESSION IX – DRUGS
AND INEFFECTIVE
ERYTHROPOIESIS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES