Last reviewed: 24 Sep 2021
Last updated: 08 Aug 2018



History and exam

Other diagnostic factors

  • history of recurrent infection
  • fatigue
  • pallor
  • history of bleeding or easy bruising
  • tachycardia
  • dyspnoea
  • persistent warts
  • hearing loss or deafness
  • short stature, pigmentation abnormalities, or urogenital abnormalities
  • nail malformations, reticular rash, oral leukoplakia, or epiphora
  • osteoporosis
  • premature hair loss/premature greying
  • hyperhidrosis
  • dysphagia
  • extensive dental caries or tooth loss
  • steatorrhoea
  • skeletal dysplasia
  • monocytopenia
  • non-tuberculous mycobacterial infections
  • pulmonary alveolar proteinosis
  • congenital lymphoedema, Emberger syndrome
  • immunodeficiency (DCML [dendritic cell, monocyte, B cell, and NK cell deficiency])

Risk factors

  • drug or toxin exposure
  • paroxysmal nocturnal haemoglobinuria (PNH)
  • recent hepatitis
  • pregnancy
  • autoimmune disease
  • family history

Diagnostic investigations

1st investigations to order

  • full blood count with differential
  • reticulocyte count
  • bone marrow biopsy and cytogenetic analyses

Investigations to consider

  • serum B12 and folate levels
  • HIV testing
  • liver function tests (LFTs)
  • autoantibody screen
  • flow cytometry for glycosylphosphatidylinositol (GPI)-anchored proteins
  • chest x-ray
  • abdominal ultrasound
  • appropriate genetic tests
  • computed tomography scan

Treatment algorithm



Judith C. W. Marsh, MD, FRCP, FRCPath

Professor of Haematology

Consultant Haematologist

Department of Haematological Medicine

King's College Hospital NHS Foundation Trust

King’s College London




JCWM has received fees for consulting for Novartis Global, Amgen, and GSK and has also consulted for Pfizer and Sanofi; received a fee for lectures given for Novartis and has also given lectures for Alexion and Sanofi; was awarded a research grant from Sanofi for King’s College London and has a research grant from GSK/Novartis awaiting final approval; and has received travel expenses from Novartis and Adienne to attend meetings.

Austin G. Kulasekararaj, MD, MRCP, FRCPath

Consultant Haematologist

Department of Haematological Medicine

King's College Hospital NHS Foundation Trust




AGK is on the Speakers' Panel and Advisory Board for Novartis, Pfizer, Alexion, and Celgene. He is an author of a reference cited in the monograph.


Professor Marsh and Dr Kulasekararaj would like to gratefully acknowledge the assistance of Dr Ziyi Lim, Dr Philippe Armand, and Professor Joseph H. Antin, previous contributors to this monograph. ZL, PA, and JHA declare that they have no competing interests.

Peer reviewers

Christoph Pechlaner, MD

Associate Professor of Medicine

Innsbruck Medical University




CP declares that he has no competing interests.

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