Autoimmune hemolytic anemia (AIHA) is a hemolytic disease caused by the production of autoantibodies against one's own red blood cells under certain pathogenic factors, which activate the complement system. Based on the temperature conditions required for the immune reaction between autoantibodies and red blood cells, this disease is generally classified into three types: (1) Warm antibody type: The autoantibodies are IgG-type incomplete antibodies, primarily causing extravascular hemolysis. If complement is involved, intravascular hemolysis may also occur. (2) Cold antibody type (cold agglutinin disease): The antibodies are IgM-type complete antibodies, often secondary to conditions such as lymphoma, mycoplasma pneumonia, or infectious mononucleosis, leading to intravascular hemolysis. (3) Paroxysmal cold hemoglobinuria: The antibodies are IgG-type cold antibodies, often associated with congenital syphilis. This section focuses on the clinically more common warm antibody type AIHA.

bubble_chart Clinical Manifestations

1. Acute type More common in children under 4 years old, some cases present as fulminant with rapid disease progression. Manifestations include shivering, fever, progressive pallor, dysphoria, vomiting, abdominal pain, headache, and occasionally hemoglobinuria. Jaundice, hepatosplenomegaly, and in severe cases, renal insufficiency presenting as oliguria or anuria, and azotemia may occur.
2. Chronic type Seen in all age groups, mostly in older children. Presents as progressive or intermittent hemolytic anemia. Anemia is generally mild, with jaundice and hepatosplenomegaly. Recurrent infections may exacerbate the condition, even leading to hemolytic crisis. A few cases may present with purpura.

bubble_chart Auxiliary Examination

1. Blood Picture In the acute type, Hb can drop as low as 20g/L, while chronic cases show milder anemia. Reticulocytes are increased, with acute cases reaching 60–80%. If the primary disease suppresses erythroid proliferation, reticulocytes may not be elevated. Peripheral blood smears reveal anisocytosis, nucleated red cells, polychromatic red cells, as well as spherocytes and red cell fragments. Leukocytosis may occur. 2. Bone Marrow Picture Erythroid hyperplasia is prominent, primarily with polychromatic normoblasts. Cabot rings, Howell-Jolly bodies, and basophilic stippling may be observed, along with increased sideroblasts. 3. Erythrocyte Fragility Test During disease progression, saline osmotic fragility increases, correlating with the number of spherocytes. 4. Serum Bilirubin Indirect bilirubin is elevated, though it may remain within the normal range in mild cases. 5. Coombs Test (Antiglobulin Test) The direct test is positive, while the indirect test may be negative or positive. Using monoclonal antiglobulin serum, three results are possible: (1) Anti-IgG positive only: IgG-type AIHA, commonly seen in secondary cases. (2) Anti-IgG and C3 positive: most frequent clinically, often seen in chronic cases. (3) Anti-C3 positive: more common in acute cases. A few cases may remain Coombs-negative due to various reasons, so a negative result does not rule out the diagnosis. Some suggest that 125I-labeled erythrocyte surface IgG measurement is more sensitive than the Coombs test.

Medical History There may be predisposing factors such as a history of medication use (e.g., penicillin, methyldopa, para-aminosalicylic acid) or viral or bacterial infections, but in some cases, no identifiable cause can be found.

bubble_chart Treatment Measures

Treatment of

(1) General Treatment: Actively control the primary disease, prevent and treat infections. For severe cases, pay attention to protecting heart and kidney functions, and prevent shock, DIC, etc. (2) Adrenal Corticosteroids: The first-line drug. It can reduce antibody production and decrease the phagocytic destruction of red blood cells with attached autoantibodies by the mononuclear-macrophage system, with confirmed efficacy. Prednisone can be administered orally at 1–2 mg/(kg·d) until hemoglobin levels return to normal, then maintained for another month before gradually tapering the dose (first reduce the daily dose by 5 mg per week until it reaches 10 mg, then continue oral administration for 4 weeks, followed by 5 mg daily for 3 months, then 2.5 mg daily for another 3 months. If no relapse occurs, the medication can be discontinued). The entire course lasts several months or longer. For a few extremely severe cases, high-dose hormone shock therapy may be necessary in the initial days, such as methylprednisolone at 20–30 mg/(kg·d), rapidly tapering the dose within 1–2 days and gradually reducing to the usual dosage in about a week, which may yield better efficacy. (3) Immunosuppressants: Usually used when hormones are ineffective. Effects generally appear after two or more weeks of use. Options include: (1) Azathioprine 2–2.5 mg/(kg·d), divided into 2–3 oral doses; (2) Cyclophosphamide 2–3 mg/(kg·d), divided into 2–3 oral doses; (3) 6-MP or 6-MG 0.5–2.5 mg/(kg·d), divided into 2–3 oral doses. (4) Blood Transfusion Therapy: Only used when severe anemia is life-threatening. To reduce complement input and avoid exacerbating hemolysis, red blood cell suspensions washed three times with saline can be transfused. Note that autoantibodies attached to the red blood cell surface may affect blood type matching accuracy, and transfused cells are prone to destruction. (5) Splenectomy: Considered for warm-antibody-type AIHA cases where hormone or immunosuppressant therapy fails after 2–4 weeks, or side effects are too severe, or repeated transfusions are required. Preoperative nuclear scanning to confirm the spleen as the primary site of red blood cell destruction further supports the indication for surgery.