Autoimmune hemolytic anemia

Background

Autoimmune hemolytic anemia (AIHA) = generation of auto-antibodies towards red blood cell membrane antigens, leady to hemolysis.
Can be primary (idopathic) or due to another disease process (e.g. malignancy, autoimmune disease, infection)

"Cold" Autoimmune Hemolytic Anemia

Cold AIHA refers to hemolytic disease caused by cold reacting autoantibodies, i.e. autoantibodies that agglutinate to RBCs at lower temperatures (usually 0°C-5°C). This is the less common than "warm" AIHA, and is typically mediated by IgM autoantibodies. When IgM autoantibodies attach to the RBCs, they cause an intravascular hemolysis, meaning that hemolysis and release of all intracellular contents occurs within the blood vessels. This results in elevated serum LDH, low haptoglobin, and presence of hemoglobinuria (due to the release of unprocessed hemoglobin into the blood stream. Causes "cold" AIHA" include:

Infection - most commonly ''Mycoplasma'' ''pneumoniae'' infection and infectious mononucleosis
Plasmacytomas - specifically Multiple Myeloma
Idiopathic

"Warm" Autoimmune Hemolytic Anemia

Autoantibodies agglutinate to RBCs at higher temperatures

IgG mediated, usually pan-reactive to patient's and transfused RBCs
Extravascular (i.e. in spleen) hemolysis--> unconjugated > conjugated hyperbilirubinemia
Haptoglobin low, LDH may be normal
Causes:
- Lymphoma, especially Non-Hodgkin's lymphoma
- Leukemia, particularly chronic lymphocytic leukemia
- Collagen vascular diseases (E.g. Systemic Lupus Erythematosus, Rheumatoid arthritis, Giant cell arteritis
- Viral-induced or HIV-associated
- Medications: methyldopa, quinidine, penicillin

Clinical Features

-Signs and symptoms of anemia (fatigue, pallor, palpitations, etc.)
-Jaundice and scleral icteris from hyperbilirubinemia
-Features related to the patient's underlying disease process that is causing their AIHA

Diagnosis

Direct Coombs test - blood sample is removed of plasma and incubated with anti-human immunoglobulin (aka "Coombs reagent"). This detects if autoantibodies are attached to RBCs or compliment. If the RBCs are coated with IgG (positive direct Coombs test), this suggests the diagnosis of "warm AIHA. If the RBCs are coated with only compliment, this suggests the diagnosis of "cold" AIHA

Treatment

Warm AIHA
-Glucocorticoids are first-line
-Splenectomy for patient's with refractory disease to glucocorticoid therapy

Cold AIHA
-Typically no treatment is necessary as disease is self-limited and recommendations to avoid cold temperatures is typically sufficient
-RBC transfusion for significant and symptomatic disease
-Glucocorticoids are not indicated