The spleen plays an important role in sickle cell disease and it is vital to understand something about how it works. This is a brief account; a recent review in the British Journal of Haematology goes into things in much greater detail. The spleen has always been a mysterious organ. It was thought in the past to be the seat of sadness or anger, but is now known to be an important part of the immune system and to act as a filter for the blood. It is usually about the size of a large orange and lies on the left hand side of the abdomen tucked up beneath the ribs, so that you cannot normally feel it. Your doctor may request an ultrasound scan to visualise the spleen and measure how large it is.
The immune function is the most important. The spleen has a vital role to play in the body’s defence against certain, very specific bacteria. These bacteria have a sticky, mucous-like capsule, which surrounds them, and which protects them against attack by the antibodies of our immune system. The importance of the spleen is that it is able to produce anti-polysaccharide, IgM antibodies, which can attack these bacteria despite this protective capsule. The bacteria can then be removed by the body before they become established and able to cause problems. The main bacteria involved are Streptococcus pneumonia (“the Pneumococcus), Nesseiria meningitidis and Haemophilus influenza. They can cause a variety of serious infections such as blood poisoning or septicaemia, pneumonia and meningitis. Apart from this unique function the spleen also has a more general role to play in the immune system because it is the site where large numbers of B and T lymphocytes live, the major antibody producing cells of the body.
In addition to it’s immune function, the spleen is also a sophisticated blood filter. Much of the blood passing through the spleen trickles slowly through a dense meshwork of cells and any contaminating particles, such as bacteria or damaged cells are removed by specialised macrophages. The filtering function of the spleen can be assessed by looking for Howell-Jolly bodies in the red cells of the blood or by counting the percentage of pitted red cells.
People who are born without a spleen, those whose spleen is removed at surgery or those whose spleen does not work are said to be asplenic or hyposplenic. The main consequence of this is that throughout their life they have an increased risk of contracting serious infections caused by the bacteria listed above. Sickle cell disease is one of the main medical conditions in which the spleen does not work properly.
Babies with severe sickle cell disease (Hb SS or Hb S-beta 0 thalassaemia) have normal spleen function at birth, but the spleen is repeatedly damaged by recurrent episodes of blood vessel blockage early in life. The slow flow of blood through the spleen creates ideal conditions for sickling and vaso-occlusion. As a result the spleen becomes progressively smaller and functioning splenic tissue is replaced by non-functional fibrous scar tissue. By the age of approximately 4 years the majority of Hb SS and Hb S-beta 0 thalassaemia children have no splenic function left at all. In less severe forms of sickle cell disease such as Hb SC and Hb S-beta + thalassaemia the situation is less clear cut; the development of splenic dysfunction is less predictable, and many individuals retain some degree of normal function throughout their life.
So, the main message is that most patients with sickle cell disease lose all, or part, of the function of their spleen and this leaves them vulnerable to serious infections. Prevention of these life threatening infections is vital and is based around three interventions. It is very important to be aware of these and to stick with them if at all possible.
1. Early treatment of an infection. The serious infections caused by a non-functioning spleen can progress very rapidly. It is very important to see your doctor urgently if you think you may have an infection so that you can be prescribed a treatment course of antibiotics. Do not delay.
2. Preventative antibiotics. This is usually penicillin V (phenoxymethylpenicillin) which is ideally taken twice every day for life. There is no convincing evidence that it is safe to stop penicillin after a certain age, or that long term use increases the risk of bacterial resistance developing. Some patients are allergic to penicillin and for them erythromycin is a good alternative. Many patients find it difficult to take penicillin regularly, every day and there are a variety of other ways of using the antibiotics, for example taking them once a day or at a higher dose only when you feel unwell. Twice every day is best.
3. Vaccination. The precise vaccination programme will vary in different centres but should include immunisation with Prevenar and Pneumovax (against the Pneumococcus), with the Hib vaccine (against Haemophilius influenzae), with the meningococcal group C conjugate vaccine (against Neisseria meningitidis) together with the flu vaccine (against influenza). Each of the vaccines must be given regularly to maintain adequate levels of immunity. Some centres will re-vaccinate on a regular basis every 5-10 years others will measure antibody levels and re-vaccinate when these fall below a given level. The exception to this is the flu vaccine which only gives short lasting protection and must be given every autumn because the strain of flu virus in circulation varies from year to year. Get vaccinated.
Avoiding serious infection in sickle cell disease is one of the most important things you can do to prevent complications – always take your antibiotics and check with your doctor to make sure that your vaccinations are up to date.
The spleen can also cause other problems in sickle cell disease, although these only affect a small number of patients. It is possible to have a crisis affecting the spleen, especially if you have Hb SC disease. This is known as a splenic infarct. The pain is felt around the lower, left chest wall and can be very severe and long lasting. The spleen can also be affected by sequestration and can cause hypersplenism, both of these are unusual complications.
During an episode of splenic sequestration the spleen rapidly increases in size, often over a matter of a few hours. A change that can result in the development of shock, with severe anaemia and low blood pressure, because of pooling of blood in the grossly enlarged spleen.
Sequestration is often precipitated by an infection of some sort. Treatment is by urgent blood transfusion to replace the blood trapped in the spleen.
Hypersplenism is when the spleen remains persistently enlarged and traps many of the red cells, white cells and platelets within it’s substance. These cells would normally circulate in the blood but in hypersplenism are retained in the spleen and as a consequence the individual may become very anaemic, with a low white cell count and platelet count. Often the only treatment here is to remove the spleen at surgery if the blood counts remain persistently very low.
The spleen and sickle cell disease: the sick(led) spleen. British Journal of Haematology, 2014; 166, 165-176. Brousse V, Buffet P and Rees D.