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/Parameter	Causes	Pathophysiology	Laboratory abnormalities	Physical examination	Treatment	Other associated abnormalities
Autoimmune hemolytic anemia	Drug-induced Immune-mediated Non-immune-mediated Infections Rheumatologic disease	Immune-mediated destruction	Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Pallor Jaundice	Removal of offending agent Steroids Alternative immunosuppression	HELLP syndrome TTP CLL
Paroxysmal cold hemoglobinuria	Production of Donath-Landsteiner antibody	Bispecific hemolysin that causes immune-mediated destruction	Indirect hyperbilirubinemia Reticulocytosis Low haptoglobin Elevated LDH	Pallor Jaundice	Removal of offending agent Steroids Alternative immunosuppression	HELLP syndrome TTP CLL
Sideroblastic anemia	Alcoholism Lead poisoning Vitamin B6 deficiency Isoniazid Chloramphenicol	Microcytic (<80 femtoliter) Or Normocytic (80-100 femtoliter)	Ringed sideroblasts in bone marrow Low vitamin B6 level High lead level	Pallor Weakness	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
Thalassemia	Genetic defect with alpha- or beta-globin production	Microcytic (<80 femtoliter)	Abnormal hemoglobin electrophoresis (in beta-thalassemia)	Irritability Growth retardation Jaundice Hepatomegaly Splenomegaly	Transfusion support Iron chelation Gene therapy if available	Extramedullary hematopoiesis
Iron deficiency anemia	Loss of iron from gastrointestinal blood loss or menstrual blood loss	Microcytic (<80 femtoliter)	Low serum iron Elevated transferrin Low transferrin saturation Low ferritin	Pallor Weakness Positive occult blood testing (if GI bleeding)	Intravenous or oral iron supplementation	Chronic blood loss
Pernicious anemia	Vitamin B12 deficiency	Macrocytic (>100 femtoliter)	Low vitamin B12 or folate level Megaloblastic anemia with hypersegmented neutrophils	Numbness Weakness Tingling Paresthesias	Vitamin B12 1000mcg daily	Autoimmune disorders

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