What are the blood tests for hemolysis (breakdown of red blood cells)?

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From the Guidelines

Blood tests for hemolysis should include lactate dehydrogenase (LDH), haptoglobin, reticulocyte count, bilirubin levels, and peripheral blood smear examination, as recommended by the most recent guidelines 1. These tests are essential for diagnosing and managing hemolysis, as they help identify the underlying cause and guide treatment.

Key Tests for Hemolysis

  • LDH: elevated during hemolysis as it's released from damaged red blood cells
  • Haptoglobin: depleted during hemolysis as it binds free hemoglobin
  • Reticulocyte count: increases as the bone marrow responds to red cell destruction
  • Bilirubin levels: rise due to increased red cell breakdown, with unconjugated bilirubin being a key indicator
  • Peripheral blood smear examination: may show fragmented red cells (schistocytes), spherocytes, or other abnormal morphologies depending on the cause of hemolysis Additional useful tests include:
  • Direct antiglobulin test (Coombs test) to detect antibody-mediated hemolysis
  • Hemoglobin electrophoresis for hemoglobinopathies
  • Tests for G6PD deficiency or other enzyme deficiencies These tests help differentiate between intravascular hemolysis (occurring within blood vessels) and extravascular hemolysis (occurring in the spleen or liver), which guides appropriate treatment 1.

Importance of Hemolysis Testing

Hemolysis testing is crucial for diagnosing conditions like autoimmune hemolytic anemia, hereditary spherocytosis, and microangiopathic hemolytic anemias, and for guiding treatment to improve patient outcomes and reduce morbidity and mortality 1. The most recent guidelines from 2021 1 provide the best evidence for the diagnostic workup of hemolysis, and should be followed in clinical practice to ensure optimal patient care.

From the Research

Blood Tests for Haemolysis

  • Laboratory tests that confirm haemolysis include:
    • Reticulocytosis
    • Increased lactate dehydrogenase
    • Increased unconjugated bilirubin
    • Decreased haptoglobin levels 2
  • The direct antiglobulin test can further differentiate immune causes from nonimmune causes of haemolysis 2
  • A peripheral blood smear should be performed when haemolysis is present to identify abnormal red blood cell morphologies 2

Classification of Haemolytic Diseases

  • Haemolytic diseases are classified into:
    • Hemoglobinopathies
    • Membranopathies
    • Enzymopathies
    • Immune-mediated anemias
    • Extrinsic nonimmune causes 2
  • Extrinsic nonimmune causes include:
    • Thrombotic microangiopathies
    • Direct trauma
    • Infections
    • Systemic diseases
    • Oxidative insults 2

Note on Relevance of Studies

  • Only one study, 2, is relevant to the topic of blood tests for haemolysis.
  • The other study, 3, discusses a case of soft tissue calcification and is not relevant to the topic of haemolysis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hemolytic Anemia: Evaluation and Differential Diagnosis.

American family physician, 2018

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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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