Hemolytic anemia

Last reviewed: 24 Apr 2022
Last updated: 30 Mar 2022
30 Mar 2022

US FDA approves new treatments for hemolytic anemia

Mitapivat is the first disease-modifying therapy approved by the US Food and Drug Administration (FDA) for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency.

Approval for mitavipat, an oral pyruvate kinase activator, was based on positive results from phase 3 trials (ACTIVATE and ACTIVATE-T), demonstrating the drug's ability to reduce hemolysis and improve anemia in PK deficiency.

Sutimlimab, a humanized monoclonal antibody that selectively targets and inhibits complement C1-activated hemolysis, is the first therapy approved by the FDA for use in patients with cold agglutinin disease (CAD).

The approval of sutimlimab was based on positive results from the 26-week open-label, single arm pivotal phase 3 study (CARDINAL) in patients with CAD with a recent history of blood transfusion.[45]

See Management: emerging

Original source of update

Summary

Definition

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 RBC membrane defects
  • paroxysmal nocturnal hemoglobinuria
  • recent exposure to cephalosporins, penicillins, quinine derivatives, or NSAIDs
  • 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 (DAT or Coombs)
  • creatinine, BUN
  • LFTs
  • Donath-Landsteiner antibody
  • Hb electrophoresis
  • flow cytometry for CD55/CD59
  • glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test and spectrophotometry
  • ANA
More investigations to consider

Treatment algorithm

ACUTE

acquired: Coombs positive

acquired: Coombs negative

inherited disorders

Contributors

Authors

John Densmore, MD, PhD

Associate Professor of Clinical Medicine

Department of Medicine

University of Virginia

Charlottesville

VA

Disclosures

JD declares that he has no competing interests.

Acknowledgements

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

Rome

Italy

Disclosures

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

Cleveland

OH

Disclosures

AL declares that he has no competing interests.

  • Hemolytic anemia images
  • Differentials

    • Anemia due to blood loss
    • Underproduction anemia
    • Transfusion reaction
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  • Guidelines

    • Recommendations regarding splenectomy in hereditary hemolytic anemias
    • Guidelines on the use of intravenous immune globulin for hematologic conditions
    More Guidelines
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