ISSN 2398-2977      

Anemia: immune-mediated

pequis

Synonym(s): Immune-mediated anemia


Introduction

  • Important cause of anemia    Anemia: overview  .
  • Group of conditions with similar clinical presentation but different etiologies/significance.
  • Red blood cells are destroyed by the animal's immune system because they have been altered in some way, either by a host protein, a drug, or a foreign antibody.
  • Extravascular hemolysis: destruction of red blood cells through tissue fixed macrophage removal in spleen, liver, bone marrow.
  • Intravascular hemolysis: the red blood cells are destroyed whilst within the vasculature.
  • Cause(adults):
    • Primary: auto-immune anemia caused by primary endogenous auto-antibody production with no apparent trigger such as infection or drug administration - this form is rare.
    • Secondary: due to coating of the red blood cells with antibodies or alteration in the red cell membrane:
      • Drug administration in which the drug coats or alters the red blood cell surface.
      • Secondary to viral or bacterial disease in which there is production of auto-antibodies secondary to infection or the infective agent directly altered the red blood cell membrane.
      • Neonatal isoerythrolysis: a distinct form of immune-mediated hemolytic anemia occurring only in foals. They ingest colostrum containing antibodies against their own red blood cells.
      • Neoplasia: if the red blood cells are passing through a large neoplasm and are damaged as they do so, or the presence of neoplasia results in the production of auto-antibodies.
    • Complement-mediated hemolysis may occur if antibodies are IgM or complement-activating IgG   IgG   bind to the red cell surface.
    • Altered red cell surface proteins not recognized as self by reticulo-endothelial immune system and those red blood cells are therefore destroyed.
  • Signs: lethargy, depression, weakness, fever, hemoglobinuria.
  • Diagnosis: blood sampling, Coombs test, tests for infectious diseases.
  • Treatment: blood transfusion, corticosteroids, halting drug administration.
  • Prognosis: very guarded.

Pathogenesis

Etiology

  • Red blood cells are destroyed by the host's immune system if they are altered in any way, either by being coated by an antibody, or if the cell membrane is disrupted. This is a normal mechanism to remove old or damaged cells, but when large numbers of cells are altered then extensive hemolysis results and anemia ensues.
  • Primary auto-antibody production.
  • Secondary immune-mediated hemolytic anemia:
    • Drugs may coat the RBCs and cause them to be destroyed, eg penicillins and trimethoprimsulfamethoxazole (TMPS).
    • Drug may complex with a carrier molecule and induce an immune response.
    • Drug may induce a true auto-immune response.
    • Immune complexes may result from infections such asStreptococcus equiand clostridial disease.
    • Neonatal colostral antibody intake.
    • Incompatible blood transfusion   Blood: transfusion   containing lytic antibody for recipient cells (or conversely recipient has antibody to donor cells)   Blood: transfusion reactions  . Either way the problem for which transfusion is given, is exacerbated.
    • Altered red cell membrane structure, usually secondary to serious internal neoplasia.
  • Red cell destruction primarily in the reticuloendothelial system, much less frequent intravascularly.

Predisposing factors

General

Specific

  • Certain blood groups more liable to neonatal isoerythrolysis, eg Aa and Qa positive foals born to Aa Qa negative mares.

Pathophysiology

  • True auto-immune hemolytic anemia   Anemia: auto-immune hemolytic (AIHA)  is rare. 
  • Failure of B cells to recognize self red cells through altered B/T cell function or through development of abnormal clones of B cells becoming abnormally reactive.
  • Secondary immune-mediated hemolytic anemia caused when antigenantibody complexes are bound to red cells surfaces.
  • Altered red cell surface antigens in disease such as lymphosarcoma    and other internal neoplasia.
  • Occasionally arise from other inflammatory diseases.
  • Hemolysis associated with IgG is known as warm hemagglutinin, and the spleen is the primary site of RBC sequestration, if it involves IgM it is said to be cold hemagglutinin disease and mainly involves the liver.

Timecourse

  • Usually abrupt onset of signs.
  • Rapid progression is characteristic.
  • Death may ensue if early treatment not instituted.
  • Some cases follow a slower course.

Epidemiology

  • Usually affect individual horses unless associated with an infectious cause, eg equine infectious anemia   Equine infectious anemia (EIA)  , piroplasmosis   Babesiosis  , equine ehrlichiosis   Anaplasmosis  .
  • Historical facts important including recent drug administration.
  • Clinical examination vital to identify possible contributing disease conditions or causative factors and eliminate other causes of profound anemia.
  • Mares that have previously produced NI foals are more likely to produce NI foals if bred with the same stallion in future.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Kendall A & Pringle J (2014) Immune-mediated haemolytic anaemia: Drug induced or not? Equine Vet Educ 26 (5), 234-236 VetMedResource.
  • Cottle H J & K J Hughes (2010) Haemolytic anaemia in a pony associated with a perivascular abscess caused by Clostridium perfringens. Equine Vet Educ 22 (1), 13-19 VetMedResource.
  • Peek S F (2010) Immune-mediated haemolytic anaemia in adult horses: Do we need to transfuse, immunosuppress or just treat the primary problem? Equine Vet Educ 22 (1), 20-22 VetMedResource.
  • Underwood C & Southwood L L (2008) Haemolytic anaemia as a complication following colic surgery in a 10-year-old Arabian stallion. Equine Vet Educ 20 (8), 422-426 VetMedResource.
  • Thomas H L & Livesey M A (1998) Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse. Can Vet J 39, 171 PubMed.
  • Robbins R L, Wallace S S, Brunner C J et al (1993) Immune-mediated haemolytic disease after penicillin therapy in a horse. Equine Vet J 25, 462 PubMed.
  • McConnico R S, Roberts M C & Tompkins M (1992) Penicillin-induced immune-mediated hemolytic anemia in a horse. JAVMA 210 (9), 1402-1403 PubMed.
  • Beck D J (1990) A case of primary autoimmune haemolytic anemia in a pony. Equine Vet J 22 (4), 292-294 PubMed.
  • Mair T S, Taylor F G & Hillyer M H (1990) Autoimmune haemolytic anaemia in eight horses. Vet Rec 126, 51 PubMed.
  • Morris D D (1989) Review of anemia in horses. Equine Pract 11, 34-46 VetMedResource.

Other sources of information

  • Carlson G P (2002) diseases of the Hematopoietic and Hemolymphatic Systems. In: Large Animal Internal Medicine. Ed: Smith B P. Chapter 35. Mosby, USA.
  • Collins J D (1975) Autoimmune haemolytic anemia in the horse. In: Proc 1st Int Symp Equine Hematol 1, 342 VetMedResource.

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