Introduction
Splenomegaly and hypersplenism can develop in association with hemolytic anemia. The spleen contains two different parts that look and function differently, the white pulp and the red pulp. The white pulp which is located more in the periphery of arteries is an immune organ consisting of lymphatic tissue.
The red pulp is lining the sinuses and cords (part of the venous system within the spleen) and is filled with macrophages and granulocytes whose function is to remove old and damaged red blood cells and old platelets (thrombocytes). The white pulp functions as an immune organ producing B cells and T cells. The B cells produce antibodies against viruses such as the flu etc. However in the case of immune hemolytic anemias with a positive Coombs’ test these B cells will produce autoantibodies directed against blood cells. The red pulp will remove antibody coated red blood cells and old and defective red blood cells. This includes inclusion bodies like Heinz bodies (globin that is insoluble) and Howell-Jolly bodies (nuclear fragments).
Hemolytic anemias from changes outside of the RBC
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Autoimmune hemolytic anemias (link accessible from “Related Topics” below)
Traumatic hemolytic anemia (link accessible from “Related Topics” below)
Splenomegaly and Hypersplenism (this page)
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When the spleen is not functioning because of fibrotic changes or when a splenectomy has been performed in the past, the hematologist will be able to tell this from a stained blood smear where Heinz bodies and Howell-Jolly bodies will be present. Splenomegaly simply means “large spleen”. This can be caused by a large number of unrelated medical conditions. Congestive disease can be found with end stage cirrhosis (Banti’s disease). Myeloproliferative diseases such as Hodgkin’s disease, leukemia, primary thrombocythemia and polycythemia vera can all develop splenomegaly as part of their illness. Infectious diseases (particularly infectious mononucleosis, bacterial endocarditis, hepatitis and psittacosis, but also tuberculosis, brucellosis, malaria and syphilis etc.) and inflammatory diseases (like sarcoidosis, lupus or Felty’s syndrome) are known causes of splenomegaly as well. Congenital forms of anemias and hemolytic anemias often have splenomegaly as part of the clinical presentation. Finally, the lipoid storage diseases (Gaucher’s, Hand-Schüller-Christian, Niemann-Pick diseases etc.) and the non lipoid storage diseases (Letterer-Siwe disease etc.) as well as amyloidosis can all cause splenomegaly.
Hypersplenism
Once splenomegaly is present, it does not seem to matter much what the underlying cause for the enlarged spleen was, but the spleen is now much more effective in filtering out red blood cells, white blood cells and platelets. Whatever cell line is removed, the bone marrow will increase production so that the loss of the cell line is compensated for (compensatory bone marrow hyperplasia). This can mask the symptoms somewhat and delay the diagnosis. Eventually though the bone marrow cannot keep up the cell production and there will be anemia (when the red blood cells are affected), leucopenia (white blood cells diminished) or thrombocytopenia (platelets affected). In summary, hypersplenism is present when there is a reduction of a line of blood cells as the result of splenomegaly.
Symptoms
The symptoms are from the underlying disease process. In addition there can be a feeling of satiety early into a meal from the pressure of the enlarged spleen on the neighboring stomach. The larger the spleen, the more fullness the patient feels even between meals. In addition there may be pain in the left upper abdomen. Infarcts can form within the spleen and this would be associated with severe left upper abdominal pain and may be mistaken first for a heart attack. If there are recurrent infections and anemia the physician often will feel for the spleen and detect the enlargement. However, studies have shown that even with the best physical examination the doctors will only pick up about 65% of the otherwise proven splenomegaly. Percussion will detect about 70% of otherwise proven splenomegaly. This simply means that physical examination has a sensitivity for detection of only 65 to 70%.
Diagnostic tests
Ultrasound examination is the method of choice as it detects 100% and also shows details of the infrastructure of the enlarged spleen (high accuracy, low cost). However, in certain cases the hematologist may want to order an MRI scan, if more details are required (clots in the portal or splenic veins). In the past nuclear scans were also performed, but this has been replaced by CT and MRI scans. Causes of the underlying illness have to be worked up with specific tests that the hematologist will choose depending on the history and the clinical findings in a particular patient. To avoid later complications a particular effort must be made to rule out an underlying or occult infection. Repeat CBC (complete blood count) tests and blood cultures should be ordered. The hematologist should also examine bone marrow samples. Blood smears, liver function tests and lymphoma screening tests (flow cytometry) are only some of the baseline tests that likely will be performed. For detection of lymphoproliferative disorders serum protein electrophoresis would be ordered. A diffuse hypergammaglobulinemia would indicate a chronic infection like tuberculosis, malaria, kalazar or brucellosis.
Treatment
Splenomegaly is merely a symptom of these other diseases that are mentioned above. Treatment is therefore directed against the underlying conditions. Splenomegaly by itself is not a threat to the patient unless there is hypersplenism present as well. If severe hypersplenism (see above) is present a hematologist needs to be consulted on an urgent basis as a decision may have to be made soon whether or not a splenectomy is needed. There is a correlation between the spleen size and the degree of the anemia. It is a difficult decision to decide when to do a splenectomy and when to keep the spleen. The spleen is a major immune organ, so removing it will weaken the immune system and be a potential risk in future to the patient. On the other hand there are conditions that are known risks and if the spleen is not taken out the patient would likely die. For instance, in Gaucher’s disease, which is a lipid storage disease, the spleen can turn 30 times the normal size and be life threatening as it causes a severe lowering of all blood cell types (called a “pancytopenia). The spleen can be removed surgically or can be radiated to “ablate” it. This renders it non functional by inducing radiation fibrosis and the blood cells can recover by either of these two treatments. The hematologist has the necessary experience that it takes in these difficult situations to know which way to go. Hereditary spherocytosis and thalassemia are two other conditions where hypersplenism can set in with a splenomegaly. Again a decision needs to be made early enough and based on a thorough investigation and assessment by a hematologist whether or not a splenectomy or radiation therapy would be beneficial to the patient. Whenever possible a splenectomy should be avoided as the spleen’s normal function is to protect the body against bacteria that are encapsulated. Patients who had a splenectomy need to be protected against these bacteria by a vaccination program. Pneumococcal vaccine, meningococcal vaccine and vaccination against Haemophilus influenzae are routinely given. This will prevent pneumococcal pneumonia, bacterial meningitis and H.influenzae pneumonia. The patient is also more prone to septicemia, which is a life threatening condition with free floating bacteria in the blood. Empiric antibiotic prophylaxis is given before high risk procedures are done like dental work, gynecological procedures, prostatic surgery, cystoscopy, bronchoscopy, bile duct surgery or procedures (ERCP), etc.
References:
1. Merck Manual (Home edition): Anemia
2. Noble: Textbook of Primary Care Medicine, 3rd ed., Mosby Inc. 2001
3. Goldman: Cecil Medicine, 23rd ed., Saunders 2007: Chapter 162 – APPROACH TO THE ANEMIAS
