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


=="Cold" Autoimmune Hemolytic Anemia==
==="Warm" 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:<br />
''Autoantibodies agglutinate to RBCs at higher temperatures''
# Infection - most commonly [[''Mycoplasma'' ''pneumoniae'']] infection and infectious [[mononucleosis]]<br />
*IgG mediated, usually pan-reactive to patient's and transfused RBCs
# Plasmacytomas - specifically [[Multiple Myeloma]]<br />
*Extravascular (i.e. in spleen) hemolysis→ unconjugated > conjugated [[hyperbilirubinemia]]
# Idiopathic
*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]]


=="Warm" Autoimmune Hemolytic Anemia==
==="Cold" Autoimmune Hemolytic Anemia===
Warm AIHA referrs to hemolytic disease caused by warm reacting autoantibodies, i.e. autoantibodies that agglutinate to RBCs at higher temperatures (usually about 37°C). This is typically mediated by IgG autoantibodies, which results in [[extravascular hemolysis]], meaning hemolysis occurs within the spleen. The IgG bound RBCs are detected by splenic macrophages, phagocytosed, and broken down ''intracellularly''. The byproduct of hemoglobin digestion is unconjugated bilirubin, which is released into the blood stream bound to albumin, and excreted by the liver. Therefore, in warm AIHA, there is a unconjugated > conjugated hyperbilirubinemia, with a relative absence of elevated LDH and low haptoglobin. Causes of warm AIHA inlcude:<br />
''Autoantibodies agglutinate at lower temperatures''
# Lymphomas (specifically [[Non-Hodgkin's lymphoma]])<br />
*IgM mediated
# Leukemias (specifically [[Chronic Lymphocytic Leukemia]])<br />
*Intravascular hemolysis→ high LDH, low haptoglobin, hemoglobinuria
# Collagen Vascular Diseases - [[Systemic Lupus Erethematosis]], [[Rheumatoid Arthritis]], [[Scleroderma]], [[Temporal Arteritis]], etc.<br />
*Causes:
# Drugs - methyldopa, quinidine, penicillin<br />
**Infection, most commonly [[Mycoplasma pneumoniae]] and [[mononucleosis]], also [[varicella]], [[listeria]], [[influenza]]
# Idiopathic
**[[Multiple myeloma]] and other plasmacytomas
**Idiopathic


==Clinical Features==
==Clinical Features==
-Signs and symptoms of anemia (fatigue, pallor, palpitations, etc.)<br />
*Signs and symptoms of [[anemia]] (fatigue, pallor, palpitations, etc.)
-Jaundice and scleral icteris from hyperbilirubinemia<br />
*[[Jaundice]] and scleral icterus
-Features related to the patient's underlying disease process that is causing their AIHA
*Signs/symptoms of underlying disease process
*Cold-type:
**Acrocyanosis, [[Raynaud’s disease|Raynaud's]], vascular occlusion with peripheral tissue ischemia


==Diagnosis==
==Differential 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
{{Anemia DDX}}


==Treatment==
==Evaluation==
Warm AIHA<br />
*CBC, LFTs, LDH, haptoglobin
-Glucocorticoids are first-line<br />
*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
-Splenectomy for patient's with refractory disease to glucocorticoid therapy<br />


Cold AIHA<br />
==Management==
-Typically no treatment is necessary as disease is self-limited and recommendations to avoid cold temperatures is typically sufficient<br />
===Warm AIHA===
-RBC transfusion for significant and symptomatic disease<br />
*Oral [[prednisone]] 1-1.5mg/kg/day for 1-3 weeks with taper after hemoglobin stable
-Glucocorticoids are '''not''' indicated
**may need several months of low dose [[prednisone]] to remain in remission
*[[Splenectomy]] and/or cytotoxic drugs for for steroid-refractory disease
*[[Plasmapheresis]] as temporizing measure for severe disease
*Transfuse [[pRBCs]] only if truly life-threatening anemia, least incompatible units possible


==Further Reading==
===Cold AIHA===
[[Paroxysmal nocturnal hemoglobinuria]] (PNH)<br />
*No treatment for mild disease
[[Systemic lupus erythematosus]]<br />
*Immunosuppressive or cytotoxic medications can be considered
[[Rheumatoid arthritis]]<br />
*[[Plasmapheresis]] for severe disease
[[Scleroderma]]
 
==Disposition==
 
==See Also==
*[[Paroxysmal nocturnal hemoglobinuria]] (PNH)
*[[Systemic lupus erythematosus]]
*[[Rheumatoid arthritis]]
*[[Scleroderma]]
 
==References==
<references/>
[[Category:Heme/Onc]]

Latest revision as of 23:57, 30 September 2019

Background

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

"Warm" Autoimmune Hemolytic Anemia

Autoantibodies agglutinate to RBCs at higher temperatures

"Cold" Autoimmune Hemolytic Anemia

Autoantibodies agglutinate at lower temperatures

Clinical Features

  • Signs and symptoms of anemia (fatigue, pallor, palpitations, etc.)
  • Jaundice and scleral icterus
  • Signs/symptoms of underlying disease process
  • Cold-type:
    • Acrocyanosis, Raynaud's, vascular occlusion with peripheral tissue ischemia

Differential Diagnosis

Anemia

RBC Loss

RBC consumption (Destruction/hemolytic)

Impaired Production (Hypochromic/microcytic)

  • Iron deficiency
  • Anemia of chronic disease
  • Thalassemia
  • Sideroblastic anemia

Aplastic/myelodysplastic (normocytic)

  • Marrow failure
  • Chemicals (e.g. ETOH)
  • Radiation
  • Infection (HIV, parvo)

Megaloblastic (macrocytic)

Evaluation

  • CBC, LFTs, LDH, haptoglobin
  • 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

Management

Warm AIHA

  • Oral prednisone 1-1.5mg/kg/day for 1-3 weeks with taper after hemoglobin stable
    • may need several months of low dose prednisone to remain in remission
  • Splenectomy and/or cytotoxic drugs for for steroid-refractory disease
  • Plasmapheresis as temporizing measure for severe disease
  • Transfuse pRBCs only if truly life-threatening anemia, least incompatible units possible

Cold AIHA

  • No treatment for mild disease
  • Immunosuppressive or cytotoxic medications can be considered
  • Plasmapheresis for severe disease

Disposition

See Also

References

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