A 32-year-old woman presents with chronic hemolytic anemia, jaundice, and a positive direct antiglobulin test (DAT). Warm-reactive IgG antibodies are detected. What is the most common cause of autoimmune hemolytic anemia in adults?

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Accepted Answer

A. Warm-reactive IgG autoantibodies. ## Warm Autoimmune Hemolytic Anemia: Most Common Type **Key Point:** Warm-reactive IgG autoimmune hemolytic anemia (WAIHA) accounts for 70–80% of all autoimmune hemolytic anemias in adults, making it the most common form. ### Classification of Autoimmune Hemolytic Anemia | Type | Antibody | Thermal Reactivity | Prevalence | Mechanism | |------|----------|-------------------|-----------|----------| | **Warm AIHA** | IgG (±C3) | Reacts at 37°C | 70–80% | Extravascular hemolysis (spleen) | | **Cold AIHA** | IgM (±C3) | Reacts at <4°C | 15–20% | Intravascular hemolysis (complement-mediated) | | **Mixed AIHA** | IgG + IgM | Both temperatures | 5% | Combined mechanism | | **Paroxysmal Cold Hemoglobinuria** | IgG (biphasic) | Cold + warm | <1% | Rare, complement-mediated | ### Warm AIHA: Pathophysiology ```mermaid flowchart TD A[IgG autoantibodies bind RBC surface]:::action --> B[Opsonization of RBCs]:::action B --> C{Splenic macrophages recognize Fc region}:::decision C -->|Phagocytosis| D[Extravascular hemolysis]:::outcome C -->|Partial destruction| E[Spherocyte formation]:::outcome D --> F[Jaundice, Dark urine, Splenomegaly]:::outcome ``` ### Clinical Features of Warm AIHA - **Onset:** Insidious (weeks to months) - **Severity:** Variable, from mild to severe - **Splenomegaly:** Common (70% of cases) - **Jaundice:** Present (unconjugated hyperbilirubinemia) - **Dark urine:** From hemoglobinuria ### Diagnostic Criteria | Test | Finding | |------|----------| | **DAT (Coombs)** | Positive (IgG ± C3) | | **Indirect bilirubin** | Elevated | | **LDH** | Elevated | | **Haptoglobin** | Decreased | | **Reticulocyte count** | Elevated (>2%) | | **Blood film** | Spherocytes, polychromasia | | **Warm antibody screen** | Positive at 37°C | **High-Yield:** **Positive DAT + elevated reticulocyte count + elevated indirect bilirubin = AIHA confirmed.** The type of antibody (warm vs. cold) determines the thermal reactivity pattern. **Clinical Pearl:** Warm AIHA is often idiopathic (50%), but can be secondary to: - Systemic lupus erythematosus (SLE) - Lymphoproliferative disorders (CLL, lymphoma) - Medications (methyldopa, penicillins) - Infections (EBV, CMV, HIV) ### Treatment Hierarchy for Warm AIHA 1. **First-line:** Corticosteroids (prednisone 1 mg/kg/day) 2. **Second-line:** Splenectomy (if steroid-dependent or resistant) 3. **Third-line:** Rituximab (anti-CD20 monoclonal antibody) 4. **Fourth-line:** Immunosuppressants (azathioprine, cyclophosphamide)

Answer

B. Complement-only (non-IgG) hemolysis

Answer

C. Cold-reactive IgM autoantibodies

Answer

D. IgA-mediated hemolysis

A 32-year-old woman presents with chronic hemolytic anemia, jaundice, and a positive direct antiglobulin test (DAT). Warm-reactive IgG antibodies are detected. What is the most common cause of autoimmune hemolytic anemia in adults?

Explanation

Warm Autoimmune Hemolytic Anemia: Most Common Type

Classification of Autoimmune Hemolytic Anemia

Warm AIHA: Pathophysiology

Clinical Features of Warm AIHA

Diagnostic Criteria

Treatment Hierarchy for Warm AIHA

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Type	Antibody	Thermal Reactivity	Prevalence	Mechanism
Warm AIHA	IgG (±C3)	Reacts at 37°C	70–80%	Extravascular hemolysis (spleen)
Cold AIHA	IgM (±C3)	Reacts at <4°C	15–20%	Intravascular hemolysis (complement-mediated)
Mixed AIHA	IgG + IgM	Both temperatures	5%	Combined mechanism
Paroxysmal Cold Hemoglobinuria	IgG (biphasic)	Cold + warm	<1%	Rare, complement-mediated

Test	Finding
DAT (Coombs)	Positive (IgG ± C3)
Indirect bilirubin	Elevated
LDH	Elevated
Haptoglobin	Decreased
Reticulocyte count	Elevated (>2%)
Blood film	Spherocytes, polychromasia
Warm antibody screen	Positive at 37°C