Snapshot A 60-year-old man presents to his primary care physician with complaints of fatigue. His family is concerned that he looks very orange. He sometimes experiences shortness of breath with physical exertion. A peripheral smear comes back with some spherocytes as well as some smudge cells. His direct Coombs test comes back positive with anti-C3 and anti-IgG. Introduction Extrinsic hemolytic anemia caused by antibodies login to view 1 more bullet Characteristics Warm Agglutinin (IgG) Cold Agglutinin (IgM) Temperature at which antibodies are most reactive to RBC Body temperature Lower temperatures (39.2°F) Chronic vs acute Chronic Acute Complement-mediated Associated conditions SLE (most common) CLL Drugs (α-methyldopa and penicillin) Mycoplasma pneumonia Infectious mononucleosis (EBV) Epidemiology AIHA (most common) More common in women Mneumonic Warm weather is GGGreat Cold weather is for ice cream, yuMMM Epidemiology Peak incidence in 50s-80s ETIOLOGY Associated conditions login to view 2 more bullets Presentation Symptoms login to view 10 more bullets Physical exam login to view 3 more bullets STUDIES Two types of Coombs test login to view 11 more bullets Characteristics Warm Agglutinin (IgG) Cold Agglutinin (IgM) Direct Coombs test + Direct Coombs test with anti-IgG Coombs reagent + Direct Coombs test (DAT) with anti-C3 Coombs reagent Indirect Coombs test + Indirect Coombs test (tests for IgG autoantibodies) - Indirect Coombs test Other tests RBCs spontaneously agglutinate at room temperature Most accurate test Cold agglutinin titer Complement level Normal C3 and C4 ↓ C3 and C4 Peripheral blood smear login to view 3 more bullets Serology showing hemolytic anemia login to view 4 more bullets Urinalysis login to view 2 more bullets Differential Cryoglobulinemia Lymphoma Raynaud's syndrome HIT Hereditary spherocytosis Treatment Prevention login to view 2 more bullets Warm agglutinin login to view 8 more bullets Cold agglutinin login to view 7 more bullets Complications Warm agglutinin login to view 2 more bullets Cold agglutinin login to view 2 more bullets Prognosis Mortality rate 10% For most patients, prognosis is good