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.
Presents with acute or subacute development of fatigue or jaundice, and may include orthostasis and mild splenomegaly.
Anemia, reticulocytosis, low haptoglobin, high LDH, and high indirect bilirubin suggest hemolysis.
Direct antiglobulin test (Coombs) is important for differentiating immune from nonimmune etiologies. Peripheral smear review is important in identifying underlying cause.
Corticosteroids are often first-line therapy in immune-mediated cases. Discontinuation of offending agents (e.g., suspected drugs) and supportive care are the mainstay of treatment for many subtypes.
Early vaccination against encapsulated organisms is important if splenectomy is possible.
Hemolytic anemia encompasses a number of conditions that result in the premature destruction of RBCs. Common causes include autoantibodies, medications, and underlying malignancy, but the condition can also result from a number of hereditary conditions, such as hemoglobinopathies.
History and exam
Key diagnostic factors
Other diagnostic factors
- shortness of breath
- active infections
- episodic dark urine (hemoglobinuria)
- triggered by exposure to cold
- 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
- Clostridium perfringens infection
- Haemophilus influenzae type B infection
- liver disease
1st investigations to order
- reticulocyte count
- peripheral smear
- unconjugated (indirect) bilirubin
Investigations to consider
- direct antiglobulin test (DAT or Coombs)
- creatinine, BUN
- Donath-Landsteiner antibody
- Hb electrophoresis
- flow cytometry for CD55/CD59
- glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test and spectrophotometry
acquired: Coombs positive
acquired: Coombs negative
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.
Pasquale Niscola, MD
PN declares that he has no competing interests.
Alan Lichtin, MD
Hematologic Oncology and Blood Disorders
Cleveland Clinic Lerner College of Medicine
AL declares that he has no competing interests.
- Anemia due to blood loss
- Underproduction anemia
- Transfusion reaction
- Recommendations regarding splenectomy in hereditary hemolytic anemias
- Guidelines on the use of intravenous immune globulin for hematologic conditions
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