What is the cause of hemolysis (breakdown of red blood cells)?

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From the Guidelines

Hemolytic conditions, such as hemolytic anemia, require prompt diagnosis and treatment to prevent severe complications, including acute kidney injury and death, and the most recent guidelines from the American Society of Hematology 2020 recommend transfusion support for patients with sickle cell disease, including extended matched red cells and avoidance of additional transfusions if possible, to reduce the risk of hyperhemolysis 1.

Key Considerations

  • Hemolytic conditions can be caused by various factors, including autoimmune disorders, infections, medications, toxins, or inherited disorders affecting red blood cell structure or function.
  • Common symptoms of hemolytic anemia include fatigue, weakness, pale skin, jaundice, and shortness of breath.
  • Treatment depends on the underlying cause and may include corticosteroids, immunosuppressants, blood transfusions, or splenectomy in severe cases.
  • Prompt diagnosis through blood tests like complete blood count, reticulocyte count, and direct Coombs test is crucial for effective management of hemolytic conditions.

Management of Hyperhemolysis

  • Hyperhemolysis can occur with no identifiable antibody and a negative direct antiglobulin test, and recognition is critical to avoid additional transfusions that may worsen the condition.
  • IVIg, high-dose steroids, eculizumab, and/or rituximab have been used to treat hyperhemolysis in patients with sickle cell disease, but the optimal management remains unclear 1.

Diagnostic Challenges

  • Pyruvate kinase deficiency is a rare cause of chronic hereditary nonspherocytic hemolytic anemia, and diagnosis can be challenging due to the wide variability of the condition and the lack of familiarity with this diagnosis even among hematologists 1.
  • A global PK deficiency International Working Group has established recommendations for the diagnosis of PK deficiency, including the use of evidence-based material and peer-reviewed publications 1.

From the Research

Definition and Classification of Hemolytic Anemia

  • Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening 2.
  • It should be part of the differential diagnosis for any normocytic or macrocytic anemia 2.
  • Hemolysis may occur intravascularly, extravascularly in the reticuloendothelial system, or both 2.

Causes and Mechanisms of Hemolytic Anemia

  • Mechanisms include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction 2.
  • Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes 2.
  • Extrinsic nonimmune causes include the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults 2.

Diagnosis of Hemolytic Anemia

  • Laboratory test results that confirm hemolysis include reticulocytosis, as well as increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels 2.
  • The direct antiglobulin test further differentiates immune causes from nonimmune causes 2, 3.
  • A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies 2.

Treatment of Hemolytic Anemia

  • Corticosteroids are the first-line treatment option for warm autoantibody-related hemolytic anemia 4, 5.
  • In patients who develop steroid side effects or do not respond adequately, other immunosuppressives may be preferred 4.
  • Rituximab or other monoclonal antibodies may be used instead of splenectomy in therapy-refractory patients 6, 5, 3.
  • Plasma exchange (PE) may be utilised in case of severe and refractory anemia, especially in the case of cardiovascular imbalance in fulminant hemolysis 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hemolytic Anemia: Evaluation and Differential Diagnosis.

American family physician, 2018

Research

Autoimmune hemolytic anemia.

Hematology. American Society of Hematology. Education Program, 2018

Research

Hemolytic anemia and plasma exchange.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2021

Research

[Autoimmune hemolytic anemia].

Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke, 2009

Research

Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review.

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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