What are the laboratory findings indicative of hemolysis (breakdown of red blood cells)?

From the Guidelines

Hemolysis labs should include a comprehensive diagnostic work-up, as recommended by the most recent guidelines 1, to ensure accurate diagnosis and management of hemolytic anemia. The diagnostic work-up for hemolysis should include:

• History and physical examination, with special consideration of new drugs, insect, spider, or snake bites
• Blood chemistry, CBC with evidence of anemia, macrocytosis, evidence of hemolysis on peripheral smear, LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin
• Disseminated intravascular coagulation (DIC) panel, which could include Prothrombin Time (PT) or International Normalized Ratio (INR), and infectious causes
• Autoimmune serology, paroxysmal nocturnal hemoglobinuria (PNH) screening, and direct and indirect bilirubin
• Direct agglutinin test, and if no obvious cause, bone marrow analysis, and cytogenetic analysis to evaluate myelodysplastic syndromes (MDS)
• Evaluation for viral or bacterial causes of hemolysis, protein electrophoresis, and cryoglobulin analysis
• Workup for bone marrow failure syndrome if refractory, including B12, folate, copper, parvovirus, iron, and thyroid, infection
• Glucose-6-phosphate dehydrogenase level, and evaluation of common drug causes of hemolysis
• Assessment of methemoglobinemia, as outlined in the guidelines 1, which provide the most up-to-date recommendations for the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy.

The guidelines 1 emphasize the importance of a thorough diagnostic work-up to ensure accurate diagnosis and management of hemolytic anemia, and to prevent potential complications. Key laboratory tests for hemolysis include:

• LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin
• CBC with evidence of anemia, macrocytosis, and evidence of hemolysis on peripheral smear
• DIC panel, and autoimmune serology
• PNH screening, and direct and indirect bilirubin
• Direct agglutinin test, and bone marrow analysis if necessary, as recommended by the guidelines 1.

From the Research

Hemolysis Labs

• Hemolysis is defined by the premature destruction of red blood cells, and can be chronic or life-threatening 2
• Laboratory test results that confirm hemolysis include:
  • Reticulocytosis
  • Increased lactate dehydrogenase
  • Increased unconjugated bilirubin
  • Decreased haptoglobin levels
• A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies 2
• The direct antiglobulin test further differentiates immune causes from nonimmune causes 2

Diagnostic Tests for Anemia

• The complete blood count with red cell indices offers clues to diagnosis 3
• The reticulocyte count serves as a useful screen for hemolysis or blood loss 3
• Testing for specific causes of the anemia is performed, and occasionally, examination of the bone marrow is required for diagnosis 3
• Molecular testing is increasingly being used to aid the diagnostic process 3

Evaluation of Suspected Anemia

• Initial evaluation consists of a thorough history and physical examination and a complete blood cell count (CBC) 4
• Careful examination of the CBC and the mean corpuscular volume provides important clues to the classification and cause of anemia 4
• Supplemental tests may include:
  • A peripheral blood smear
  • Reticulocyte count
  • Iron panel
  • Levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 4

Laboratory Approach to Hemolytic Anemia

• The diagnostic workup or laboratory approach for hemolytic anemias is based on methodical step-wise testing 5
• This includes red blood cell morphology, hematological indices with increased reticulocyte count along with clinical features of hemolytic anemias 5
• If conventional laboratory tests are unable to detect the underlying cause of hemolysis, genetic testing is recommended 5