Autoimmune hemolytic anemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S; Shyam Patel [2]

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Differentiating Autoimmune hemolytic anemia from other Diseases

Diagnosis is made by first ruling out other causes of hemolytic anemia, such as G6PD, thalassemia, sickle-cell disease, etc.

Characteristic	Causes	Pathophysiology	Laboratory abnormalities	Physical examination	Therapy	Other associations
Autoimmune hemolytic anemia	Abnormal immune activation Failure of self vs. non-self recognition Infections Chronic lymphocytic leukemia Non-Hodgkin's lymphoma Rheumatologic disease	Polyclonal antibody production that binds to and targets red blood cells for destruction intravascurly or extravascularly	Positive Coombs' test for IgG Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Pallor Jaundice Shortness of breath Tachypnea	Removal of offending agent Corticosteroids Cyclophosphamide Cyclosporine A Azathioprine Rituximab Splenectomy	Hemolysis can occur at warm or cold temperatures
Paroxysmal cold hemoglobinuria	Production of Donath-Landsteiner antibody, triggered by viral or bacterial infection	Biphasic hemolysin (IgG) that binds red blood cells and low temperatures and triggers complement-mediated intravascular hemolysis at warm temperatures	Positive Donath-Landsteiner antibody Microscopic hematuria Negative Coombs' test for IgG or C3d Negative cold agglutinin titer Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Hematuria in the presence of cold weather Jaundice	Removal of offending agent Steroids Alternative immunosuppression	Associated with syphilis Maternal IgG can cross the placenta and affect the fetus
Hereditary spherocytosis	Mutation in ankyrin Mutation in alpha- or beta-spectrin Mutation in band 3 Mutation in protein 4.2	Diminished membrane integrity Increased red blood cell fragility Splenic destruction of deformed red blood cells	Positive eosin-5-maleimide binding to red blood cells Positive osmotic fragility testing Spherocytes on peripheral blood smear	Pallor Jaundice Splenomegaly	Removal of offending medication High-dose vitamin B6 (up to 200mg daily) Avoidance of splenectomy Symptomatic transfusion support with iron chelation as needed	Can be autosomal dominant or recessive
Pernicious anemia	Autoimmune gastritis Production of anti-intrinsic factor antibodies Production of anti-parietal cell antibodies	Impaired vitamin B12 absorption due to absence of intrinsic factor	Low vitamin B12 level Presence of anti-intrinsic factor antibodies Presence of anti-parietal cell antibodies	Gastrointestinal discomfort Weakness Tingling Paresthesias	Lifelong vitamin B12 therapy (1000mcg daily)	Associated with diabetes, thyroid disease, vitiligo and other autoimmune conditions
Chronic lymphocytic leukemia	Mutations in hematopoietic stem cells and B lymphocytes	Clonal proliferation of malignant B lymphocytes	Elevated absolute lymphocyte count Anemia (Rai stage III) and thrombocytopenia (Rai stage IV)	Numbness Weakness Tingling Paresthesias	Vitamin B12 1000mcg daily	Secondary autoimmune hemolytic anemia occurs in advanced CLL; treatment with corticosteroids or anti-leukemic therapy will correct the underlying anemia

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