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anemia hemolitik
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Autoimmune Hemolytic AnemiaHematology > Autoimmune Hemolytic Anemia
Summary
Description
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.
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
A hematocrit of <20, rapidly developing anemia, declining functional status, or evidence of end-organ damage requires urgent action
Admit patient to hospital for observation and potential transfusion Evaluate patient for underlying 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); and evidence of RBC autoantibodies/complement (usually indicated by a positive direct Coombs test). Note: the direct Coombs test is falsely negative in a small percentage of AIHA
Though usually idiopathic, AIHA is commonly associated with infection, autoimmune disease, lymphoproliferative disorders, and some drugs
Warm AIHA and cold agglutinin disease are most common among adults over age 50, in whom the diseases are usually chronic and relapsing; PCH, a rare disorder occurring most commonly in children, usually resolves on its own
Medical intervention is usually not necessary in the many patients who present with a mild hemolytic anemia; 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, activate macrophages, and induce phagocytosis
Low hematocrit: <37% (female) to <40% (male) Elevated reticulocyte count: >2.4% (female) to >2.6% (male) Elevated reticulocyte index: >3% Spherocytes or RBC aggregates are visible on the peripheral blood smear The most clinically important AIHAs are warm AIHA, chronic cold agglutinin
disease, and paroxysmal cold hemoglobinuria
Warm AIHA:
Direct Coombs test is positive for immunoglobulin G (IgG), complement (C3d), or both
Spherocytes present on the peripheral blood smear Phagocytized RBCs are typically sequestered in the spleen Most patients quickly respond to corticosteroids, though the disorder is chronic and
often relapsing Refractory cases require prolonged immunosuppression or may undergo splenectomy;
life-threatening cases may require transfusion
Chronic cold agglutinin disease:
Positive direct Coombs test rarely detects cold-reactive IgM, but always detects C3d bound to RBC membrane
RBC aggregates seen on peripheral blood smear Typically, cold agglutinin titer is very high Idiopathic form of disease is frequently recurrent condition and often responds to cold
avoidance; exacerbations are intermittent Critical to explore diagnosis of B-cell lymphoma, 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, not spleen In presence of B-cell neoplasm, 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; routine tests do not pick up pathological Donath-Landsteiner autoantibody
Most often appears postviral in children and young adults Symptoms may include fever, chills, abdominal distress, nausea, 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, but usually short-lived and self-limited Treatment includes: cold avoidance; supportive care; transfusions to alleviate
symptoms; corticosteroids rarely useful In rare cases can progress to renal failure
Causes
Common causes
Warm AIHA:
Idiopathic: warm autoantibody IgG, its complement (C3d), or both, coat the red cell membrane and at 37°C induce phagocytosis
Secondary: warm antibodies produced by lymphoproliferative disorders (e.g. non-Hodgkin's lymphoma, chronic lymphocytic leukemia (CLL); collagen vascular/autoimmune diseases (e.g. systemic lupus erythematosus (SLE); and HIV infection
Cold agglutinin disease:
Idiopathic: the IgM autoantibody has an affinity for RBCs at cold temperatures (0ºC-18ºC); at warmer temperatures (37ºC, or 98.6ºF), when the two have no particular affinity, the IgM antibody can come off the RBC, but the remaining complement sticks. Hemolysis occurs as the liver and spleen remove complement-coated RBCs
Secondary: cold autoantibodies produced by infections such as Epstein-Barr virus, Mycoplasma pneumoniae, and infectious mononucleosis; and 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), which produce
the Donath-Landsteiner antibody
Rare causes
Secondary Warm AIHA:
Certain drugs that induce hemolysis as a side effect (e.g. the antineoplastics cladribine and fludarabine)
Evans' syndrome (concomitant immune thrombocytopenic purpura and warm antibody AIHA)
Immunologic diseases such as agammaglobinuria, hypogammaglobulinemia, dysglobulinemias, and immune deficiency syndromes
Monoclonal gammopathy of undetermined significance (MGUS) Gastrointestinal diseases, including ulcerative colitis
Secondary chronic cold agglutinin disease:
B-cell malignancies such as CLL, lymphomas, or Waldenström macroglobinuria Certain prescription medications, including alpha-methyldopa, high-dose penicillin,
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, such as SLE Lymphoproliferative disorders, such as non-Hodgkin's lymphoma, CLL
Secondary chronic cold agglutinin disease:
B-cell malignancies such as CLL, lymphomas, or Waldenström macroglobinuria
Secondary paroxysmal cold hemoglobinuria:
Viral infection (particularly in children and young adults) Syphilis
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, which
induces PCH) Cold temperature (induces IgM activation in cold agglutinin disease)
Epidemiology
Incidence and prevalence
Incidence
Figures are unreliable and, for all AIHAs, range from one new case per 75,000-80,000 in the general population per year to one per 300,000.
Prevalence
Warm AIHA: 1-2 cases per 100,000 in the general population.
Frequency
Warm AIHA is the most common, 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, in perhaps 1% of all AIHAs
Demographics
Age
Warm AIHA afflicts people of all ages, 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;
spontaneous remission occurs in most children
Gender
More women than men suffer with warm AIHA and chronic cold agglutinin disease.
Race
No particular racial group appears more prone to AIHA than any other.
Genetics
There is no known genetic predisposition to AIHA, though risk factors for AIHA include a family history of autoimmune diseases, such as SLE, rheumatoid arthritis, and glomerulonephritis.
Socioeconomic status
No socioeconomic group appears more prone to AIHA than any other.
Codes
ICD-9 code
283.0 Autoimmune hemolytic anemia.
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, Autoimmune Hemolytic (Quick Reference)Ferri: Ferri's Clinical Advisor 2013, 1st ed.
Autoimmune Hemolytic Anemia (includes Table)Bope and Kellerman: Conn's Current Therapy 2012, 1st ed.
Epidemiology
Epidemiology of AIHAFerri: Ferri's Clinical Advisor 2013, 1st ed.
Etiology
Etiology and Pathophysiology of AIHAMcPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 22nd ed.
Etiology of AIHA (includes Table)Kliegman: Nelson Textbook of Pediatrics, 19th ed.
Diagnosis
Clinical Findings of Warm AIHAHoffman: Hematology: Basic Principles and Practice, 5th ed.
Clinical Manifestations of AIHAKliegman: Nelson Textbook of Pediatrics, 19th ed.
Treatment & Management
Clinical Management of Warm-Antibody AIHABope and Kellerman: Conn's Current Therapy 2012, 1st ed.
Therapy for AIHAHoffman: Hematology: Basic Principles and Practice, 5th ed.
Patient Education
Drugs
Prednisone
http://emedicine.medscape.com/article/955266-treatment#a1128
Kliegman: Nelson Textbook of Pediatrics, 19th ed.