Last reviewed: 18 Aug 2021
Last updated: 05 Mar 2020



History and exam

Key diagnostic factors

  • fatigue
  • dyspnoea on exertion
  • pica
  • restless legs syndrome
  • nail changes
  • dysphagia

Other diagnostic factors

  • impaired muscular performance
  • glossitis and angular stomatitis
  • gastric difficulties
  • hair loss
  • rectal lesion on examination
  • growth impairment
  • cognitive and behavioural impairment
  • heart failure
  • recurrent infections

Risk factors

  • pregnancy
  • vegetarian and vegan diet
  • menorrhagia
  • hookworm infestation
  • haemodialysis
  • coeliac disease
  • gastrectomy/achlorhydria
  • non-steroidal anti-inflammatory drug (NSAID) use
  • black women and Mexican women
  • low socioeconomic status postnatal
  • obesity
  • Helicobacter pylori infection

Diagnostic investigations

1st investigations to order

  • haemoglobin and haematocrit
  • platelet count
  • MCV
  • MCH
  • MCHC
  • red cell distribution width (RDW)
  • peripheral blood smear
  • reticulocyte count
  • serum iron
  • total iron-binding capacity (TIBC)
  • transferrin saturation
  • serum ferritin
  • coeliac serology
  • urinalysis
  • Helicobacter pylori testing

Investigations to consider

  • urease breath test
  • autoimmune gastritis testing
  • upper gastrointestinal (GI) endoscopy (gastroscopy)
  • small-bowel biopsy
  • lower gastrointestinal (GI) endoscopy (colonoscopy)
  • double contrast barium enema and sigmoidoscopy
  • transferrin receptor-ferritin index
  • bone marrow biopsy
  • monitored trial of iron
  • faecal occult blood tests

Emerging tests

  • urinary hepcidin
  • percentage of hypochromic erythrocytes
  • reticulocyte haemoglobin content
  • erythrocyte protoporphyrin

Treatment algorithm



Atul Mehta, MD

Consultant Haematologist

Lysosomal Storage Disorders Unit

Department of Haematology

Royal Free Hospital




AM declares that he has no competing interests.


Dr Atul Mehta would like to gratefully acknowledge Dr Martina Murphy, Dr Marc Zumberg, and Dr Rebecca Fischer Connor, previous contributors to this topic.


MZ declares that he is medical director for NCF Diagnostics and DNA Technologies, and a consultant for Alexion Pharmaceuticals. MM and RFC declare that they have no competing interests.

Peer reviewers

Carlos Aravena, MD

Internal Medicine Instructor

Member of Evidence Based Medicine Unit

Catholic University of Chile




CA declares that he has no competing interests.

Jim Murray, MBBS

Consultant Haematologist

Clinical Haematology

University Hospital Birmingham NHS Trust




JM declares that he has no competing interests.

Ajay Kumar, MD, FACP

Medical Director

Blood Management

Cleveland Clinic




AK has received a fee for speaking about perioperative blood management from Ortho-Biotech, and has also received reimbursement from for the education webcast of the same presentation.

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