Hemolytic anemia differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]

Overview

The differential diagnosis for hemolytic anemia is broad and includes a variety of conditions that affect red blood cells. Nutritional deficiencies and thalassemias are important components of the differentiation. Certain laboratory tests and physical exam features can help to distinguish these conditions. The treatment of these conditions are quite different, so it is important to distinguish hemolytic anemia from other causes of anemia or other conditions that present similarly.

Differentiating Hemolytic anemia from other Diseases

Characterisitc/Parameter	Etiology	Physical examination	Mean corpuscular volume	Laboratory abnormalities	Treatment	Other associated abnormalities
Hemolytic anemia	Drug-induced Immune-mediated Non-immune-mediated Infections Rheumatologic disease	Pallor Jaundice	Normocytic	Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Removal of offending agent Steroids Alternative immunosuppression	HELLP syndrome TTP CLL
Sideroblastic anemia	Alcoholism Lead poisoning Vitamin B6 deficiency Isoniazid Chloramphenicol	Pallor Weakness	Microcytic Normocytic	Ringed sideroblasts in bone marrow Low vitamin B6 level High lead level	Removal of offending medication High-dose vitamin B6 (up to 200mg daily) Avoidance of splenectomy Symptomatic transfusion support with iron chelation as needed	Myelodysplastic syndrome Myeloproliferative neoplasm Iron overload
Anemia of chronic disease	Chronic kidney disease Rheumatologic disease Cancer HIV Chronic infection; excess release of IL-1 and IL-6	Pallor Weakness	Normocytic	Elevated ESR and CRP Elevated hepcidin Low serum iron Low transferrin Elevated ferritin	Treatment of the underlying cause; erythropoiesis-stimulating agents Supportive red blood cell transfusions	Inflammatory bowel disease
Thalassemia	Genetic defect with alpha- or beta-globin production	Irritability Growth retardation Jaundice Hepatomegaly Splenomegaly	Microcytic	Abnormal hemoglobin electrophoresis (in beta-thalassemia)	Transfusion support Iron chelation Gene therapy if available	Extramedullary hematopoiesis
Iron deficiency anemia	Loss of iron from gastrointestinal blood loss or menstrual blood loss	Pallor Weakness Positive occult blood testing (if GI bleeding)	Microcytic	Low serum iron Elevated transferrin Low transferrin saturation Low ferritin	Intravenous or oral iron supplementation	Chronic blood loss
Erythropoietin deficiency	Chronic kidney disease or other renal dysfunction	Pallor Weakness Signs of chronic kidney disease	Normocytic	Low erythropoietin level	Epoetin alfa 50-100 units/kg 3 times weekly Darbepoietin 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks	Dialysis dependence Myelodysplastic syndrome
Vitamin B12 or folate deficiency	Pernicious anemia Diphyllobothrium latum infection Nutritional deficiency Crohn's disease of terminal ileum	Numbness Weakness Tingling Paresthesias	Macrocytic	Low vitamin B12 or folate level Megaloblastic anemia with hypersegmented neutrophils	Vitamin B12 1000mcg daily Folate 1mg daily	Neuropathy

Table legend: HELLP, hemolysis/elevated liver enzymes/low platelets; TTP, thrombotic thrombocytopenic purpura; CLL, chronic lymphocytic leukemia