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Autoimmune Hemolytic Anemia

Hematology > Autoimmune Hemolytic Anemia


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Autoimmune hemolytic anemia (AIHA) is caused by autoantibody-induced hemolysis (the premature destruction of circulating red blood cells); usually idiopathic, it is also associated with infection, lymphoproliferative disorders, autoimmune diseases, and some drugs Hallmark findings include: anemia with elevated reticulocyte count in the absence of blood loss; a positive direct antiglobulin (Coombs) test; and spherocytes or RBC aggregates on the peripheral blood smear Autoimmune hemolytic anemia is classically divided into two groups: warm and cold disease In warm autoimmune hemolytic anemia: autoantibody immunoglobin G (IgG) attacks red blood cells (RBCs); patients are usually over age 50; typically treated with corticosteroids and therapies for underlying diseases In chronic cold agglutinin disease: cold-activated immunoglobin M (IgM) and complement (C3d) coat RBCs and trigger hemolysis; patients usually over age 50; sometimes resolves with cold avoidance; rarely progresses to renal failure Paroxysmal cold hemoglobinuria (PCH): rare disease induced most often by postviral Donath-Landsteiner autoantibody at cold temperatures in children; often acute and severe, though usually short-lived and self-limited; rarely progresses to renal failure, frank lymphoma, or death

Synonyms Immediate action
If severe anemia suspected - e.g. extreme pallor, somnolence, obtundation, tachycardia, breathlessness at rest, postural hypotension, angina - advise hospitalization for potential transfusion.
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Order complete blood count and start intravenous line Draw blood for type and cross-match If patient's hemoglobin is low (<4g/dL), pulmonary edema is present, or cardiac or cerebral function is threatened, this is a medical emergency and transfusion is necessary If cross-match is problematic, transfuse best possible match; transfused RBCs will not hemolyze faster than the patient's own RBCs

If rare aplastic crisis is suspected (hemoglobin low, reticulocyte count near zero) advise hospitalization for potential transfusion as this is a medical emergency.

Urgent action

and induce phagocytosis Low hematocrit: <37% (female) to <40% (male) Elevated reticulocyte count: >2. in whom the diseases are usually chronic and relapsing. AIHA is commonly associated with infection. medication history Key points     The diagnosis of AIHA must meet two criteria: evidence of hemolysis (anemia plus elevated reticulocyte count in the absence of blood loss). chronic cold agglutinin disease. Note: the direct Coombs test is falsely negative in a small percentage of AIHA Though usually idiopathic. and some drugs Warm AIHA and cold agglutinin disease are most common among adults over age 50. autoimmune disease.4% (female) to >2. and paroxysmal cold hemoglobinuria Warm AIHA:      Direct Coombs test is positive for immunoglobulin G (IgG). PCH. usually resolves on its own Medical intervention is usually not necessary in the many patients who present with a mild hemolytic anemia. or evidence of end-organ damage requires urgent action Admit patient to hospital for observation and potential transfusion Evaluate patient for underlying infection.6% (male) Elevated reticulocyte index: >3% Spherocytes or RBC aggregates are visible on the peripheral blood smear The most clinically important AIHAs are warm AIHA.   A hematocrit of <20. and evidence of RBC autoantibodies/complement (usually indicated by a positive direct Coombs test). but always detects C3d bound to RBC membrane . or both Spherocytes present on the peripheral blood smear Phagocytized RBCs are typically sequestered in the spleen Most patients quickly respond to corticosteroids. a rare disorder occurring most commonly in children. therapy becomes necessary when anemia is significant Background Cardinal features Autoimmune hemolytic anemia (AIHA):       RBC destruction is caused by autoantibodies and/or complement that coat the membrane of the cell. complement (C3d). lymphoproliferative disorders. rapidly developing anemia. though the disorder is chronic and often relapsing Refractory cases require prolonged immunosuppression or may undergo splenectomy. declining functional status. life-threatening cases may require transfusion Chronic cold agglutinin disease:  Positive direct Coombs test rarely detects cold-reactive IgM. activate macrophages.

chemotherapy or immunotherapy may help Exposure to cold can prompt sudden drop in hematocrit and induce renal failure Paroxysmal cold hemoglobinuria:            Diagnosis generally relies on clinical presentation.g. but usually short-lived and self-limited Treatment includes: cold avoidance. or 98.6ºF). its complement (C3d). Mycoplasma pneumoniae. Hemolysis occurs as the liver and spleen remove complement-coated RBCs Secondary: cold autoantibodies produced by infections such as Epstein-Barr virus. or both. at warmer temperatures (37ºC. nausea. exacerbations are intermittent Critical to explore diagnosis of B-cell lymphoma.g. leg/back pain Signs may include jaundice and hemoglobinuria IgG detected in serum Direct Coombs test is usually negative for pathological IgG and complement Indirect Coombs test is negative Diagnosis is confirmed with test for hallmark Donath-Landsteiner autoantibody Often acute and severe. chronic lymphocytic leukemia (CLL). routine tests do not pick up pathological Donath-Landsteiner autoantibody Most often appears postviral in children and young adults Symptoms may include fever. collagen vascular/autoimmune diseases (e. cold agglutinin titer is very high Idiopathic form of disease is frequently recurrent condition and often responds to cold avoidance. nonHodgkin's lymphoma. not spleen In presence of B-cell neoplasm. and HIV infection Cold agglutinin disease:   Idiopathic: the IgM autoantibody has an affinity for RBCs at cold temperatures (0ºC18ºC). abdominal distress. but the remaining complement sticks. coat the red cell membrane and at 37°C induce phagocytosis Secondary: warm antibodies produced by lymphoproliferative disorders (e. which will determine therapy Corticosteroids are usually not helpful Splenectomy is rarely beneficial (unless splenic lymphoma) because RBCs destroyed primarily by C3d activation are sequestered in the liver. transfusions to alleviate symptoms. supportive care. and lymphoproliferative . chills. when the two have no particular affinity. and infectious mononucleosis. the IgM antibody can come off the RBC.        RBC aggregates seen on peripheral blood smear Typically. systemic lupus erythematosus (SLE). corticosteroids rarely useful In rare cases can progress to renal failure Causes Common causes Warm AIHA:   Idiopathic: warm autoantibody IgG.

disorders. or Waldenström macroglobinuria Certain prescription medications. which produce the Donath-Landsteiner antibody Rare causes Secondary Warm AIHA:      Certain drugs that induce hemolysis as a side effect (e. lymphomas. such as SLE Lymphoproliferative disorders. such as non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL) Paroxysmal cold hemoglobinuria:   Idiopathic: Donath-Landsteiner autoantibody Secondary: viral infections (particularly in children and young adults). hypogammaglobulinemia. high-dose penicillin. CLL Secondary chronic cold agglutinin disease:  B-cell malignancies such as CLL. lymphomas. and certain second and third generation cephalosporins Mumps Secondary paroxysmal cold hemoglobinuria:   Syphilis Measles or measles vaccination Serious causes Secondary warm AIHA:   Connective tissue/autoimmune diseases. or Waldenström macroglobinuria Secondary paroxysmal cold hemoglobinuria:   Viral infection (particularly in children and young adults) Syphilis .g. dysglobulinemias. and immune deficiency syndromes Monoclonal gammopathy of undetermined significance (MGUS) Gastrointestinal diseases. the antineoplastics cladribine and fludarabine) Evans' syndrome (concomitant immune thrombocytopenic purpura and warm antibody AIHA) Immunologic diseases such as agammaglobinuria. including ulcerative colitis Secondary chronic cold agglutinin disease:    B-cell malignancies such as CLL. including alpha-methyldopa. such as non-Hodgkin's lymphoma.

and glomerulonephritis. in perhaps 1% of all AIHAs Demographics Age    Warm AIHA afflicts people of all ages. though risk factors for AIHA include a family history of autoimmune diseases. for all AIHAs.000 in the general population per year to one per 300. rheumatoid arthritis. range from one new case per 75. Race No particular racial group appears more prone to AIHA than any other. spontaneous remission occurs in most children Gender More women than men suffer with warm AIHA and chronic cold agglutinin disease.000.000 in the general population.000-80. such as SLE. which induces PCH) Cold temperature (induces IgM activation in cold agglutinin disease) Epidemiology Incidence and prevalence Incidence Figures are unreliable and.Contributory or predisposing factors     B-cell malignancy (produces hemolysis-inducing autoantibodies) Family or personal history of autoimmune disease (produces hemolysis-inducing autoantibodies) Viral infection in children (produces the Donath-Landsteiner autoantibody. representing 50-70% of all AIHAs It is estimated that chronic cold agglutinin disease makes up 16-32% of all AIHAs Paroxysmal cold hemoglobinuria occurs rarely. Frequency    Warm AIHA is the most common. Genetics There is no known genetic predisposition to AIHA. but its incidence increases with age and peaks in midlife Chronic cold agglutinin disease predominates among patients in their 50s and 60s Paroxysmal cold hemoglobinuria is usually a disorder of children or young adults. . Prevalence Warm AIHA: 1-2 cases per 100.

Epidemiology Epidemiology of AIHA Ferri: Ferri's Clinical Advisor 2013. Etiology Etiology and Pathophysiology of AIHA McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods. Clinical Manifestations of AIHA Kliegman: Nelson Textbook of Pediatrics. 19th ed. 1st ed. 1st ed. Codes ICD-9 code 283. Diagnosis Clinical Findings of Warm AIHA Hoffman: Hematology: Basic Principles and Practice. Etiology of AIHA (includes Table) Kliegman: Nelson Textbook of Pediatrics. .0 Autoimmune hemolytic anemia. 22nd ed. 1st ed. 19th ed. Autoimmune Hemolytic (Quick Reference) Ferri: Ferri's Clinical Advisor 2013. 5th ed. Autoimmune Hemolytic Anemia (includes Table) Bope and Kellerman: Conn's Current Therapy 2012. Read more about Autoimmune hemolytic anemia from this First Consult monograph: Diagnosis | Differential diagnosis | Treatment | Summary of evidence | Outcomes | Prevention | Resources More Key Resources Overview Anemia.Socioeconomic status No socioeconomic group appears more prone to AIHA than any other.

1st Kliegman: Nelson Textbook of Pediatrics. Patient Education Drugs  Prednisone http://emedicine.Treatment & Management Clinical Management of Warm-Antibody AIHA Bope and Kellerman: Conn's Current Therapy 2012. . 5th ed. 19th ed. Therapy for AIHA Hoffman: Hematology: Basic Principles and Practice.