Last reviewed: 6 Nov 2021
Last updated: 08 Aug 2019



History and exam

Key diagnostic factors

  • presence of risk factors
  • family history of alpha-thalassaemia
  • symptoms of anaemia
  • splenomegaly

Other diagnostic factors

  • childhood or young adulthood
  • symptoms of gallstones
  • growth retardation
  • history of prior iron supplementation
  • jaundice
  • mild dysmorphic facial features
  • extramedullary haematopoiesis

Risk factors

  • ethnicity from a geographic malarial area
  • positive family history

Diagnostic investigations

1st investigations to order

  • haemoglobin (Hb)
  • mean corpuscular volume (MCV)
  • mean corpuscular haemoglobin (MCH)
  • RBC count
  • peripheral smear
  • reticulocyte percentage
  • serum iron
  • serum ferritin

Investigations to consider

  • brilliant cresyl blue staining of red blood cells
  • haemoglobin electrophoresis
  • Hb fractionation by high-performance liquid chromatography (HPLC)
  • gap-PCR
  • multiplex ligation-dependent probe amplification (MLPA)
  • direct sequencing
  • MRI (hepatic or cardiac)
  • superconducting quantum interference devices (SQUID)
  • liver biopsy

Treatment algorithm



Janet L. Kwiatkowski, MD, MSCE


Thalassemia Program

Children’s Hospital of Philadelphia

Professor of Pediatrics

Perelman School of Medicine

University of Pennsylvania




JLK has participated in research trials of iron chelation sponsored by Novartis and ApoPharma, and has consulted for Ionis Pharmaceuticals, bluebird bio, Agios, and Celgene.


Dr Janet L. Kwiatkowski would like to gratefully acknowledge Dr Elizabeth A. Price and Dr Stanley L. Schrier, the previous contributors to this topic.


EAP declares that she has no competing interests. SLS has received NIH research funds, has received funds for organizing an educational symposium, and is an author of a number of references cited in this topic.

Peer reviewers

David H. K. Chui, MD, FRCPC

Professor of Medicine

Boston University School of Medicine




DHKC is an author of a number of references cited in this topic. He has received research grants or salary from the US National Institutes of Health greater than 6 figures USD.

Piero Giordano, PhD

Professor of Clinical Biochemical Molecular Genetics

Human and Clinical Genetics Department

Leiden University Medical Center


The Netherlands


PG declares that he has no competing interests.

Cornelis Harteveld, PhD

Clinical Molecular and Biochemical Geneticist

Department of Clinical Genetics

Leiden University Medical Center


The Netherlands


CH declares that he has no competing interests.

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