Autoimmune Hemolytic Anemia

• There are two (2) types of autoantibody:

◦ The cold antibodies:

‣ These are anti red blood cell autoantibodies that only bind at significantly below normal body
temperature.
‣ Therefore the extremities are particularly affected.
‣ These antibodies are usually of the IgM class.

◦ The warm antibodies:

‣ These are anti red blood cell autoantibodies that bind at normal body temperatures.
‣ These are usually of the IgG class.

• Following binding of IgM or IgG autoantibodies to the surface of the red blood cells, the classical pathway of
complement can become activated leading to the generation of the membrane attack complex (MAC).

• This will cause lysis of the red blood cells.

• In addition, phagocytic cells with Fc receptors on their cell surface can take up erythrocytes that have been
coated with antibody, and this again will lead to the destruction of those red blood cells.

• One can test for the presence of these autoantibodies using a test called the Coombs test.

• There are two different versions of this test:

◦ Direct test:
‣ A blood sample from the patient and the presence of autoantibodies that are already coating the red
blood cells are identified.
‣ One detects the presence of these autoantibodies that have already coated the red blood cells, using a
second antibody - an anti-human immunoglobulin.
‣ This will cross link together the antibodies on the surface of the red blood cells causing agglutination
which can be visualized by the eye.

◦ Indirect test:
‣ One looks for the presence of the autoantibody itself, free autoantibody that is not bound to the
erythrocytes.
‣ One can take this antibody from the serum of patients, mix it with red blood cells.
‣ If the autoantibody has specificity for red blood cells, this anti red blood cell autoantibody will bind to
the red blood cells.
‣ This autoantibody can then again be detected by using a second antibody, an anti-human
immunoglobulin.
‣ Upon adding the anti-human immunoglobulin, there will be agglutination which can be visualized by
simply looking at the slide on which this test is being carried out.
Pernicious Anemia -

• There is a autoimmune attack that prevents the absorption of vitamin B12 from the gut.

• In the normal individual, ingested vitamin B12 is picked up by intrinsic factor in the stomach.

• This complex of vitamin B12 bound to intrinsic factor is then absorbed from the gut and can be used in the
development of red blood cells.

• However in pernicious anemia, there are autoantibodies being produced.

• One of those autoantibodies is against the parietal cell H+ K+ ATPase.

• This leads to a reduced production of intrinsic factor.

• And there are also autoantibodies against intrinsic factor itself.

• This means that vitamin B12 is not absorbed from the gut resulting in anemia.

Autoimmune Thrombocytopenia Purpura -

• Platelets are affected.

• There are autoantibodies to the platelet glycoproteins GPIIb-IIIa and GPIb-IX.

• These are removed and destroyed by splenic macrophages and liver Kupffer cells.

• So following binding of these autoantibodies to the platelets, the complex of the autoantibody together with the
platelet is recognized by Fc gamma receptors on the surface of these phagocytic cells and the platelets are
destroyed, resulting in autoimmune thrombocytopenic purpura.