What are the initial steps and tests for diagnosing and managing hemolytic anemia?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 10, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

The initial steps for diagnosing hemolytic anemia involve a comprehensive approach beginning with a thorough history and physical examination, followed by laboratory testing, as outlined in the most recent guidelines 1. The diagnostic work-up should include a complete blood count (CBC) to confirm anemia and assess red blood cell indices, as well as specific tests for hemolysis such as reticulocyte count, lactate dehydrogenase (LDH), indirect bilirubin, and haptoglobin levels 1.

Key Diagnostic Tests

  • A peripheral blood smear examination is essential to identify abnormal red cell morphology such as spherocytes, schistocytes, or bite cells.
  • Additional diagnostic tests include direct antiglobulin test (Coombs test) to detect immune-mediated hemolysis, hemoglobin electrophoresis for hemoglobinopathies, and enzyme assays like G6PD for inherited enzyme deficiencies.
  • Disseminated intravascular coagulation panel, which could include Prothrombin Time and International Normalized Ratio (PT/INR), infectious causes, autoimmune serology, and paroxysmal nocturnal hemoglobinuria screening should also be considered 1.

Management

Management depends on the underlying cause but may include treating infections, discontinuing offending medications, transfusion support with packed red blood cells for severe anemia (hemoglobin <7 g/dL or symptomatic patients), and specific treatments based on etiology 1. For autoimmune hemolytic anemia, prednisone at 1-1.5 mg/kg/day is typically the first-line therapy, with folic acid supplementation (1 mg daily) often recommended to support increased erythropoiesis 1.

Severe or Refractory Cases

Severe or refractory cases may require immunosuppressants, rituximab, splenectomy, or plasmapheresis depending on the specific type and severity of hemolytic anemia, with the most recent guidelines recommending permanent discontinuation of immune checkpoint inhibitors and administration of prednisone 1-2 mg/kg/d in cases of grade 3 or 4 hemolytic anemia 1.

From the FDA Drug Label

8 Hematologic Disorders Idiopathic thrombocytopenic purpura in adults Secondary thrombocytopenia in adults Acquired (autoimmune) hemolytic anemia Erythroblastopenia (RBC anemia) Congenital (erythroid) hypoplastic anemia

The initial steps and tests for diagnosing and managing hemolytic anemia are not explicitly stated in the provided drug label. However, it is mentioned that prednisone is indicated for acquired (autoimmune) hemolytic anemia.

  • The diagnosis of hemolytic anemia would typically involve laboratory tests, but these are not specified in the label.
  • Management may involve the use of prednisone, as indicated in the label, but the specific steps and tests are not provided 2.

From the Research

Initial Steps for Diagnosing Hemolytic Anemia

  • The diagnosis of hemolytic anemia should be considered in patients presenting with normocytic or macrocytic anemia 3.
  • A thorough history and physical examination, along with a complete blood cell count (CBC), are essential initial steps in evaluating suspected anemia 4.
  • Laboratory test results that confirm hemolysis include reticulocytosis, increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels 3, 5, 6.

Tests for Diagnosing Hemolytic Anemia

  • A peripheral blood smear should be performed to identify abnormal red blood cell morphologies 3, 4.
  • The direct antiglobulin test (DAT) is used to differentiate immune causes from nonimmune causes of hemolytic anemia 3, 6.
  • The reticulocyte count serves as a useful screen for hemolysis or blood loss 7.
  • Supplemental tests may include iron panel, vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin levels 4.

Classification and Management of Hemolytic Anemia

  • Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes 3.
  • Immune causes of hemolytic anemia include autoimmune hemolytic anemia, drugs, and delayed hemolytic transfusion reactions 6.
  • Non-immune causes include the hemoglobinopathies (such as sickle cell disease) and microangiopathic hemolytic anemias (such as disseminated intravascular coagulation) 6.
  • Early supportive care in hemolytic anemia is important and may involve blood transfusions as well as interventions to slow the rate of hemolysis, such as steroids in autoimmune hemolytic anemia 6.

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

Anemia: Evaluation of Suspected Anemia.

FP essentials, 2023

Research

Hemolytic anemia.

American family physician, 2004

Research

Anemia: Evaluation and Diagnostic Tests.

The Medical clinics of North America, 2017

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.