Internal Medicine · Year 3 · from Internal Medicine

Case 2: Autoimmune Hemolytic Anemia

Patient Demographics

  • Age: 48 years
  • Sex: Female
  • Occupation: Accountant

Chief Complaint

"I'm turning yellow and my urine looks like tea."

History of Present Illness

The patient presents with a 10-day history of progressive fatigue, dark urine, and yellowing of her eyes and skin. She first noticed the dark urine about a week ago and thought she was dehydrated, but it has persisted despite increased fluid intake. Three days ago, her husband noticed her eyes were yellow. She has also developed upper abdominal fullness and mild left-sided discomfort. She denies fever, chills, recent travel, or known sick contacts. She has no history of liver disease or hepatitis. Past medical history is significant for systemic lupus erythematosus diagnosed 5 years ago, currently in remission on hydroxychloroquine. She has had no recent medication changes.

Vital Signs

  • Temperature: 99.8 degrees F (37.7 degrees C)
  • Blood pressure: 110/68 mmHg
  • Heart rate: 104 bpm
  • Respiratory rate: 18/min
  • Oxygen saturation: 97% on room air

Physical Examination

General: Jaundiced, fatigued-appearing female HEENT: Scleral icterus, pale conjunctivae Cardiovascular: Tachycardic, regular rhythm, systolic flow murmur Pulmonary: Clear bilaterally Abdomen: Soft, palpable spleen tip 3 cm below costal margin, no hepatomegaly, no tenderness Extremities: No edema, no rash Skin: Jaundice, no petechiae or purpura

Laboratory Findings

Complete Blood Count:

  • Hemoglobin: 6.8 g/dL (severe anemia)
  • Hematocrit: 20%
  • MCV: 108 fL (elevated - macrocytic due to reticulocytosis)
  • WBC: 8,200/mcL
  • Platelets: 186,000/mcL
  • Reticulocyte count: 14% (markedly elevated - appropriate marrow response)
  • Reticulocyte production index: 3.5 (elevated, indicating adequate marrow response)

Hemolysis Labs:

  • LDH: 842 U/L (elevated, normal <250)
  • Indirect bilirubin: 4.8 mg/dL (elevated)
  • Direct bilirubin: 0.6 mg/dL (normal)
  • Haptoglobin: < 10 mg/dL (undetectable - consumed by free hemoglobin)
  • Direct antiglobulin test (Coombs): POSITIVE for IgG and C3

Peripheral Blood Smear:

  • Spherocytes (numerous)
  • Polychromasia (reflecting reticulocytosis)
  • Occasional nucleated RBCs
  • No schistocytes

Additional Studies:

  • ANA: Positive at 1:640 (known positive for SLE)
  • Anti-dsDNA: Elevated at 180 IU/mL (suggests SLE flare)
  • C3: 58 mg/dL (low, consumed)
  • C4: 8 mg/dL (low, consumed)

Diagnosis

Warm autoimmune hemolytic anemia (AIHA) secondary to systemic lupus erythematosus (Evans syndrome if associated with immune thrombocytopenia)

Evidence supporting diagnosis:

  1. Hemolytic anemia confirmed by: elevated LDH, elevated indirect bilirubin, undetectable haptoglobin, elevated reticulocyte count
  2. Autoimmune etiology confirmed by: positive direct Coombs test for IgG and C3
  3. Warm AIHA (IgG-mediated) indicated by: IgG positivity, spherocytes on smear, splenomegaly
  4. Secondary to SLE: known SLE history, elevated anti-dsDNA, low complement

Management

First-line therapy:

  1. Prednisone 1 mg/kg/day (approximately 60-80 mg daily)
  • Continue until hemoglobin stabilizes > 10 g/dL
  • Then slow taper over 4-6 months
  1. Folic acid 1 mg daily (increased folate demand from reticulocytosis)

Transfusion considerations:

  1. Transfuse packed red blood cells for symptomatic anemia or hemoglobin < 7 g/dL
  • Cross-matching may be difficult due to panagglutinin (autoantibody reacts with all donor cells)
  • Use "least incompatible" units
  • Transfuse slowly with close monitoring

SLE management:

  1. Rheumatology consultation for SLE flare management
  2. Consider additional immunosuppression (azathioprine, mycophenolate) as steroid-sparing agents

Second-line options if steroid-refractory:

  1. Rituximab (anti-CD20, depletes B cells producing autoantibodies)
  2. Splenectomy (removes site of RBC destruction and autoantibody production)
  3. IVIG (temporary benefit, not first-line for warm AIHA)

Monitoring:

  1. Daily hemoglobin initially
  2. LDH and reticulocyte count to monitor for hemolysis resolution
  3. Repeat Coombs test (may remain positive even after clinical improvement)

Clinical Pearl

Warm autoimmune hemolytic anemia is characterized by IgG autoantibodies that bind red blood cells optimally at body temperature (37 degrees C). The antibody-coated cells are recognized by Fc receptors on splenic macrophages, which remove portions of the membrane, creating spherocytes. These rigid spherocytes are then trapped and destroyed on subsequent splenic passages (extravascular hemolysis). The positive direct Coombs test is the key diagnostic finding, detecting IgG and/or complement on the red cell surface. In this case, the association with SLE is important - secondary causes of AIHA include autoimmune diseases, lymphoproliferative disorders, and medications. The low complement levels and elevated anti-dsDNA suggest that the AIHA is occurring in the context of an SLE flare.

Clinical Image

Image Description: Peripheral blood smear demonstrating features of hemolytic anemia with spherocytes (round cells lacking central pallor) and polychromasia (bluish discoloration indicating reticulocytes), characteristic findings in autoimmune hemolytic anemia.

Attribution: Image from Wikimedia Commons. Licensed under CC BY-SA 4.0. Source: https://commons.wikimedia.org/wiki/File:Iron_deficiency_anemia_blood_film.jpg

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