AIHAs = DAT+

This post is about autoimmune haemolytic anaemias.

AIHAs = antibody production against self RBCs.
AIHAs are characterised by a positive DAT (direct antiglobulin test), a.k.a. the Coombs' test.

Differential diagnosis of spherocytes = hereditary spherocytosis or haemolytic anaemia. Distinguish with DAT.

AIHAs are divided into 'warm' and 'cold' types, depending on whether the antibody reacts more strongly with RBCs at 37 or at 4 degrees Celsius.

Warm AIHAs

The most common antibody is IgG, though sometimes IgA and IgG with complement is found. The IgGs attach to RBCs, leaving their Fc portion exposed. The Fc region is recognized and grabbed onto by Fc receptors found on monocytes and macrophages in the spleen (RES). These cells will pick off portions of the RBC membrane, almost like they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes to maintaim the same volume. Spherocytes are not as flexible as normal RBCs, and will be singled out for destruction in the red pulp of the spleen as well as other portions of the RES. The RBCs trapped in the spleen cause the spleen to enlarge, leading to the splenomegaly often seen in these patients. (Wikipedia)

IgG is a monomer, so there is no RBC agglutination in warm AIHA.

Lab findings are typical of an extravascular haemolytic anaemia with spherocytosis in the peripheral blood. DAT is positive as a result of IgG, IgG with complement or IgA on the cells. The antibodies both on the cell surface and free in serum are best detected at 37 degrees.

Rx:

1. Remove the underlying cause e.g. methyldopa.
2. Corticosteroids - start with prednisolone 60mg/d and taper. Those with predominantly IgG on cells do best whereas those with complement often respond poorly, both to steroids and splenomegaly.
3. Splenectomy if steroids fail to maintain satisfactory Hb level.
4. Immunosuppression when everything else fails, e.g. azathioprine, cyclophosphamide.
5. Monoclonal antibodies - anti-CD20 (rituximab) and anti-CD52 (Campath-1H).
6. Folic acid.
7. Blood transfusion if anaemia severe and causing symptoms. The blood should be the least incompatible and if the specificity of the autoantibody is known, donor blood is chosen that lacks the relevant antigen(s). The patients readily make alloantibodies against donor cells.
8. High-dose Ig has been used but with less success than in ITP.

Cold AIHAs
The antibody attaches to RBCs mainly in the peripheral circulation where the blood temperature is cooler.

The antibody is usually IgM (a polymer) and binds to RBCs best at 4 degrees.

IgM antibodies are highly efficient at fixing complement and both intravascular and extravascular haemolysis can occur. (Incomplete)