What is the difference between alloimmune and autoimmune hemolytic (Hemolytic) anemia as diagnosed by the Coombs test?

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: May 8, 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 Coombs test is a crucial diagnostic tool for identifying alloimmune and autoimmune hemolytic anemias, and its use is recommended in patients with suspected hemolytic anemia, particularly those with a history of autoimmune disease or chronic lymphocytic leukemia, as stated in the 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update 1.

Diagnostic Approach

The diagnostic work-up for autoimmune hemolytic anemia should include a thorough history and physical examination, blood chemistry, complete blood count (CBC) with evidence of anemia, and tests for hemolysis, such as lactate dehydrogenase (LDH), haptoglobin, bilirubin, and reticulocyte count, as recommended by the American Society of Clinical Oncology clinical practice guideline 1.

Treatment Options

Treatment for autoimmune hemolytic anemia depends on the type and severity of the disease, but typically includes corticosteroids like prednisone (1-2 mg/kg/day) for warm autoimmune hemolytic anemia, with rituximab (375 mg/m² weekly for 4 weeks) added for refractory cases, as suggested by recent studies 1.

Key Considerations

  • The direct Coombs test is positive when antibodies are already attached to red blood cells, while the indirect test detects free antibodies in serum.
  • Autoimmune hemolytic anemia can be classified as warm (IgG antibodies active at body temperature) or cold (IgM antibodies active at lower temperatures).
  • Transfusions may be necessary in life-threatening situations, though finding compatible blood can be challenging due to the presence of autoantibodies.
  • Recent studies have highlighted the importance of considering immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, including hematologic toxicities such as hemolytic anemia 1.

From the Research

Alloimmune and Autoimmune Hemolytic Anemia

  • Alloimmune hemolytic anemia is not directly discussed in the provided studies, however, autoimmune hemolytic anemia (AIHA) is thoroughly explained.
  • AIHA is caused by auto-antibodies directed against self red blood cell (RBC) surface antigens, leading to intravascular or extravascular hemolysis 2.
  • The diagnosis of AIHA is based on the direct antiglobulin test (DAT), which is typically positive with anti-IgG antisera in warm AIHA and anti-C3d in cold agglutinin disease (CAD) 3.

Coombs Test

  • The Coombs test, also known as the antiglobulin test, is essential for the diagnosis of AIHA 4.
  • The test has false negative and false positive rates in about 2-4% and 8% of all cases respectively 4.
  • A positive Coomb's antiglobulin test in the presence of hemolysis is the cornerstone of diagnosis for warm AIHA 4.

Treatment of Autoimmune Hemolytic Anemia

  • Corticosteroids are the first-line therapy for warm AIHA 2, 3, 5.
  • Rituximab is the preferred second-line treatment for primary warm AIHA and first-line treatment for primary cold agglutinin disease (CAD) 5, 6.
  • The treatment of AIHA is still not evidence-based, and recommendations are often based on expert opinions and national guidelines 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Autoimmune hemolytic anemia].

Vnitrni lekarstvi, 2018

Research

Autoimmune hemolytic anemia.

Indian journal of pediatrics, 1998

Research

Autoimmune hemolytic anemia.

Hematology. American Society of Hematology. Education Program, 2018

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.