Last reviewed: 19 Sep 2021
Last updated: 14 Apr 2021



History and exam

Key diagnostic factors

  • parent(s) diagnosed with sickle cell anemia, other sickle cell disease, or sickle cell trait
  • persistent pain in skeleton, chest, and/or abdomen
  • dactylitis

Other diagnostic factors

  • high temperature
  • pneumonia-like syndrome
  • bone pain
  • visual floaters
  • tachypnea
  • failure to thrive
  • pallor
  • jaundice
  • tachycardia
  • lethargy
  • protuberant abdomen, often with umbilical hernia
  • cardiac systolic flow murmur
  • maxillary hypertrophy with overbite
  • shock

Diagnostic investigations

1st investigations to order

  • DNA-based assays
  • hemoglobin isoelectric focusing (Hb IEF)
  • cellulose acetate electrophoresis
  • high-performance liquid chromatography (HPLC) fractionation
  • hemoglobin solubility testing
  • peripheral blood smear
  • CBC and reticulocyte count
  • iron studies

Investigations to consider

  • pulse oximetry
  • plain x-rays of long bones
  • bacterial cultures
  • chest x-ray

Treatment algorithm



Sophie Lanzkron, MD, MHS


Sickle Cell Center for Adults

Associate Professor of Medicine and Oncology

Johns Hopkins Medicine




SL has been the site principal investigator on several industry-funded studies with the following companies: Pfizer, Selexys, AstraZeneca, and Prolong. SL is a site principal investigator for Global Blood Therapeutics, Novartis, Shire, Ironwood, Imara and Bluebird Bio. She is chair of the Adjudication Committee for Novo Nordisk and Bluebird Bio and is a consultant for Pfizer. SL is an author of more than one reference in this topic. SL’s institution has received grants from Pfizer, Ironwood, Global Blood Therapeutics, NIH, PCORI and HRSA for research. She has an interest in a trust holding stocks in Pfizer and Teva.


Dr Sophie Lanzkron would like to gratefully acknowledge Dr Channing Paller, a previous contributor to this topic.


CP declares that she has no competing interests.

Peer reviewers

James Bradner, MD

Instructor in Medicine

Division of Hematologic Neoplasia

Dana-Farber Cancer Institute




JB declares that he has no competing interests.

Adrian Stephens, MB BS, MD, FRCPath

Consultant Haematologist

University College London Hospitals




AS declares that he has no competing interests.

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