Hemolytic anemia

Last reviewed: 23 Aug 2023
Last updated: 09 Nov 2022



History and exam

Key diagnostic factors

  • pallor
  • jaundice
More key diagnostic factors

Other diagnostic factors

  • fatigue
  • shortness of breath
  • dizziness
  • splenomegaly
  • active infections
  • episodic dark urine (hemoglobinuria)
  • triggered by exposure to cold
Other diagnostic factors

Risk factors

  • autoimmune disorders
  • lymphoproliferative disorders
  • prosthetic heart valve
  • family origin in Mediterranean, Middle East, Africa, or Southeast Asia
  • family history of hemoglobinopathy or red blood cell membrane defects
  • paroxysmal nocturnal hemoglobinuria
  • recent exposure to cephalosporins, penicillins, quinine derivatives, or nonsteroidal anti-inflammatory drugs
  • recent exposure to naphthalene or fava beans
  • thermal injury
  • exceptional exertion
  • recent exposure to nitrites, dapsone, ribavirin, or phenazopyridine
  • recent paraquat ingestion
  • malaria
  • babesiosis
  • bartonellosis
  • leishmaniasis
  • Clostridium perfringens infection
  • Haemophilus influenzae type B infection
  • liver disease
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC
  • MCHC
  • reticulocyte count
  • peripheral smear
  • unconjugated (indirect) bilirubin
  • LDH
  • haptoglobin
  • urinalysis
More 1st investigations to order

Investigations to consider

  • direct antiglobulin test (Coombs)
  • creatinine, BUN
  • LFTs
  • Donath-Landsteiner antibody
  • Hb electrophoresis
  • flow cytometry for CD55/CD59
  • glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test and spectrophotometry
  • antinuclear antibody
More investigations to consider

Treatment algorithm


acquired: direct antiglobulin test (Coombs) positive

acquired: direct antiglobulin test (Coombs) negative

inherited disorders



John Densmore, MD, PhD

Associate Professor of Clinical Medicine

Department of Medicine

University of Virginia




JD declares that he has no competing interests.


Dr John Densmore would like to gratefully acknowledge Dr Michelle Loch, a previous contributor to this monograph. ML declares that she has no competing interests.

Peer reviewers

Pasquale Niscola, MD

Hematology Unit

Sant'Eugenio Hospital




PN declares that he has no competing interests.

Alan Lichtin, MD

Staff Hematologist-Oncologist

Hematologic Oncology and Blood Disorders

Cleveland Clinic

Associate Professor

Internal Medicine

Cleveland Clinic Lerner College of Medicine




AL declares that he has no competing interests.

  • Hemolytic anemia images
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    • Underproduction anemia
    • Transfusion reaction
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  • Guidelines

    • Diagnosis and treatment of autoimmune hemolytic anemia in adults
    • Recommendations regarding splenectomy in hereditary hemolytic anemias
    More Guidelines
  • Videos

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    Peripheral venous cannulation: animated demonstration

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