Q: My 34 years old wife is suffering from auto-immune haemolytic anaemia for the last one and half years. Firstly, she was treated with Omnocortil. After four months, her haemoglobin level rose to 14.2 from 6.6. Then the doctor reduced the dosage of medicine. But after that her haemoglobin level again dropped to 7. Then the doctor increased the dosage of omnocortil from 10 mg to 15 mg and started Azoran (50 mg). Slowly and gradually her medicine (omnocortil) has been stopped after two months but Azoran is being continued. After that her haemoglobin level increased to 11.5. But after a month, the doctor reduced Azoran (50 mg) to 25 mg and started folic acid. But the haemoglobin level again reached to 8 within a month. The doctor told us that now he can’t increase the dosage of medicines due to their side effects. The next solution, which he recommended was splenectomy. How can my wife’s haemolytic anaemia be managed?

A:Haemolysis is the premature break down of red blood cells. This can lead to anemia (hemolytic anemia) when the bone marrow cannot compensate for the red cell loss. Clinical presentation of a patient depends on whether the onset of haemolysis is gradual (chronic) or abrupt (acute) and on the severity of red cell break down.

Haemolytic anaemias may be due to a large number of hereditary or acquired causes, one of which is immune destruction of red cells. In auto-immune hemolytic anaemias (AIHA), antibodies (proteins that can react with an antigen on the surface of the red cell) usually of the IgG or IgM type, bind to the surface of RBCs. The red cells then stick together (agglutinate); they rupture (lyse) or are destroyed in the spleen. This may be due to several causes – a) Idiopathic (no obvious cause) seen in more than 50% cases, b) Secondary to an underlying disease, usually an autoimmune disease (like systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, a malignancy etc.) or c) it may be drug induced. It is important to investigate if the patient has been taking a drug that is known to cause haemolysis. In nearly 50% of cases, no cause may be found.

Treatment of auto-immune haemolytic anaemia (AIHA) depends upon the symptoms, clinical state of the patient (primary or secondary to some other disease) and the degree of hemolysis. It may require immediate transfusion in case of a sudden severe attack or modulation of the immune system’s production of autoantibody and destruction of antibody-coated red cells. Corticosteroids are the first-line of treatment but their side effects preclude long-term use. Intravenous gammaglobulins are effective in some patients. Immunomodulation using cytotoxic drugs like cyclophosphamide, chlorambucil, azathioprine or 6-mercaptopurine is reserved for refractory patients – those who have not responded to splenectomy or cannot undergo splenectomy or have serious side effects with steroids. Splenectomy has been in use for many years and it is done in cases who do not respond to steroids or who require doses greater than 20 mg/day or those with serious side effects of steroids. Splenectomy is effective in about 50 to 60 percent of the time in IgG antibody diseases but is not usually effective in IgM antibody haemolysis. It is of benefit in these people because the spleen behaves like a sieve and if it is removed, even though the RBCs are coated by antibodies, they are no longer caught and destroyed in the spleen. The procedure is avoided in children under 6 years of age and the elderly. Patients are usually immunised with pneumococcal and meningococcal vaccines 2-3 weeks prior to the procedure. Response to splenectomy cannot be predicted but about 60% patients have excellent initial response to it and may require low dose steroids for maintenance.

There are some patients in whom splenectomy, use of immunosuppressives like azathioprine, cyclosporine A, or cyclophosphamide, or immunomodulatingagents, such as intravenous immunoglobulin, have been used frequently, alone or in combinations, with the aim of reducing steroid dependence and controlling haemolysis. However, these therapies are not consistently effective and present a risk of infectious complications due to their profound immunosuppression. In such instances there has been a trial of monoclonal antibodies like rituximab and alemtuzumab and these have shown great promise. You need to discuss this with your doctor who will be able to advise.