What is the laboratory workup for hemolysis (breakdown of red blood cells)?

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From the Guidelines

The laboratory workup for hemolysis should include a comprehensive evaluation with history and physical examination, blood chemistry, CBC with peripheral smear, LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin, as well as additional tests such as autoimmune serology, PNH screening, and direct and indirect bilirubin, as recommended by the most recent guidelines 1. The workup should start with a thorough history and physical examination, considering new drugs, insect, spider, or snake bites, and proceed with blood chemistry tests, including CBC with evidence of anemia, macrocytosis, and evidence of hemolysis on peripheral smear.

  • Key laboratory tests include:
    • LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin to assess the extent of hemolysis
    • Disseminated intravascular coagulation (DIC) panel, which could include Prothrombin Time (PT) and International Normalized Ratio (INR), to evaluate for coagulopathy
    • Autoimmune serology to identify potential autoimmune causes
    • Paroxysmal nocturnal hemoglobinuria (PNH) screening to rule out this rare but important condition
    • Direct and indirect bilirubin, direct agglutinin test, and bone marrow analysis if no obvious cause is found, to further investigate the underlying cause of hemolysis
  • Additional tests may be necessary based on the suspected etiology, such as glucose-6-phosphate dehydrogenase levels for enzymatic defects, hemoglobin electrophoresis for hemoglobinopathies, and evaluation for common drug causes, as outlined in the guidelines 1. The goal of this comprehensive workup is to differentiate between intravascular and extravascular hemolysis, identify the underlying cause, and guide appropriate management to improve patient outcomes, as supported by the latest evidence 1.

From the Research

Laboratory Workup for Hemolysis

The laboratory workup for hemolysis involves several tests to confirm the breakdown of red blood cells and to differentiate between various causes of hemolysis. Some of the key tests include:

  • Reticulocytosis, which indicates an increase in immature red blood cells [(2,3,4)]
  • Increased lactate dehydrogenase, which is a marker of intravascular hemolysis [(2,3)]
  • Increased unconjugated bilirubin, which is a sign of hemolysis [(2,3)]
  • Decreased haptoglobin levels, which is a marker of hemolysis [(2,3)]
  • Direct antiglobulin test, which differentiates between immune and non-immune causes of hemolysis [(2,3)]
  • Peripheral blood smear, which helps to identify abnormal red blood cell morphologies [(2,3)]

Additional Tests

Other tests that may be performed as part of the laboratory workup for hemolysis include:

  • Hemoglobin electrophoresis, which helps to diagnose hemoglobinopathies 4
  • Genetic testing, which may be necessary to diagnose certain genetic causes of hemolysis 4
  • Molecular testing, which can aid in the diagnosis of specific causes of anemia 5
  • Bone marrow examination, which may be required in some cases to diagnose the underlying cause of hemolysis 5

Interpretation of Results

The interpretation of laboratory results is crucial in the diagnosis and management of hemolysis. The results of these tests should be interpreted in the context of the patient's clinical presentation and medical history 6. A comprehensive clinical and laboratory evaluation is necessary to determine the underlying cause of hemolysis and to guide treatment 3.

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

Laboratory Approach to Hemolytic Anemia.

Indian journal of pediatrics, 2020

Research

Anemia: Evaluation and Diagnostic Tests.

The Medical clinics of North America, 2017

Research

The chemical and laboratory investigation of hemolysis.

Advances in clinical chemistry, 2019

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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