All you need to know about the spleen

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 meningitisApart 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.

The red pulp is the main filter of the spleen where the blood entering the spleen passes slowly down the red pulp cords before squeezing through tiny pores to re-enter the venous circulation. The white pulp contains dark staining follicles where the immune cells are concentrated.

The red pulp is the main filter of the spleen, blood entering the spleen passes slowly down the red pulp cords before squeezing through tiny pores to re-enter the venous circulation. The white pulp is the immune factory and contains dark staining follicles or nodules where the immune cells are concentrated.

This is a high powered view of a blood film from a patient with sickle cell anaemia. The double arrow is pointing to a sickled red cell and the single arrow to a red cell containing a Howell-Jolly body, stained dark purple and lying near the edge of the cell. A Howell-Jolly body is the remanent of the red cell's nucleus which is normally removed in the spleen.

This is a high powered view of a blood film from a patient with sickle cell anaemia. The double arrow is pointing to a sickled red cell and the single arrow to a red cell containing two Howell-Jolly bodies, stained dark purple and lying near the edge of the cell. A Howell-Jolly body is the remanent of the red cell’s nucleus which is normally removed in the spleen.

Pitted red cells can only be visualised using a special microscope (interference light microscopy or Normarsky optics). The pits are not really pits but small vesicles just underneath the red cell membrane

Pitted red cells can only be visualised using a special microscope (interference light microscopy or Normarsky optics). The “pits” are not really pits but small vesicles just underneath the red cell membrane which increase in number as the red cell gets older. The more pitted red cells the less effective is spleen function.

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.

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Fever is a classic sign of infection, along with feeling shaky or trembling, weakness, generalised muscle aching, vomiting and diarrhoea. These symptoms may be accompanied by the typical features of a painful crisis.

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.

The mother of this little child is being taught how to feel for her babies spleen on the left side of the abdomen . If it seems larger than normal she will be told to bring the baby straight to hospital.

The mother of this little child is being taught how to feel for her baby’s spleen on the left side of the abdomen . If it seems larger than normal she will be told to bring the baby straight to hospital.

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.

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About rogerjamos

I am a consultant haematologist who has worked in Hackney, London, UK with patients who have sickle cell disease for many years. Knowledge is power; the hope is that this blog will empower patients by putting them in touch with contemporary research into sickle cell disease and facilitating informed discussion on the issues raised. Dr Roger Amos MA, MD, FRCPath
This entry was posted in sickle cell disease. Bookmark the permalink.

3 Responses to All you need to know about the spleen

  1. Lisa Rose says:

    Hello Dr. Amos,
    It took me quite a bit longer than normal to read this, but nevertheless, it was terrific as usual! I was wondering if you had read anything about the new theory on the role of platelets in VOC and how elevated platelets due to splenectomy could have an exponential effect on the frequency and duration of pain crises? I was at a pharmaceutical conference in NYC last month and Eli Lilly presented some impressive research on a theory that ADP is not only released when blood vessels are damaged but also as sickle cells become more damaged…thus “accidentally” activating nearby platelets. The platelets activate around the sickle cells and a VOC forms that is much more intense than with solely sickle cells and potentially takes longer to break up. I am quite fascinated by these findings as it could really take SCD research and targeted approaches to treatment into a different, fresh direction. I also wonder if it would deter physicians from removing the entire spleen if a partial removal is possible. What are your thoughts on this?
    Lisa Rose
    HOPE for SCD

    • rogerjamos says:

      Thank you as ever for the comments Hope for Sickle Cell. I don’t know a lot about the role of platelets in vaso-occlusive crises but will give it some thought and let you know.

      • rogerjamos says:

        Hope for Sickle Cell raised the issue of the involvement of platelets in a sickle cell crisis. Here are some thoughts. It has been known for a long time that a sickle cell crisis does not only involve sickled red cells but also activated white cells and platelets, the question is whether this involvement is critical to the vaso-occlusive process or a peripheral manifestation of only scientific interest.

        There is no doubt that blood platelets are activated in patients with sickle cell disease and they are also present in increased numbers in the blood. This platelet activation is probably secondary to the many other changes in the blood seen in a patient with sickle cell including, changes to the red cell membrane, chronic inflammation, chronic haemolysis with free haemoglobin in the plasma and endothelial dysfunction. The activated platelets contribute to the overall pro-coagulant state, meaning that the blood of someone with sickle cell is primed to clot easily, and will therefore be one factor in the increased incidence of arterial thromboses (strokes) and venous thromboses (deep vein thrombosis or DVT and pulmonary emboli). This analysis implies that the platelet activation is secondary to the other changes induced by sickle cell and that attempting to reverse the platelet activation would not therefore be likely to have any benefit on the sickling process itself.

        In the past this has certainly been the case and treatment of patients with anti-platelet agents, like simple aspirin or dipyridamole, has not been helpful. However, recently it has been found that the anti-platelet drug, prasugrel, maybe helpful. Prasugrel is related to the drugs clopidogrel and ticlopidine, which are commonly used in patients with heart disease to prevent occlusion or blockage of the coronary arteries. The drugs work by binding to and blocking the P2Y12 receptor for ADP. ADP is one of the critical chemicals which promote platelet aggregation, by reducing binding of ADP the level of platelet activation is down regulated and the platelets become less likely to clump, or aggregate, together to form a clot. In 2013 Wun et al reported a trial of prasugrel in patients with sickle cell disease during which they demonstrated significant platelet inhibition and a trend towards decreased frequency and intensity of pain in the treatment arm of the trial. Unfortunately, the effect on pain did not reach statistical significance. A trial of prasugrel in children with sickle cell disease is currently enrolling to see whether these results can be duplicated and whether the effects on pain can be shown to be real and statistically significant.

        So, although the use of drugs which inhibit platelet function does not attack the underlying problem in sickle cell disease, in that they do not stop the red cells from sickling, it may be that there is some benefit to be derived from their use, perhaps by preventing incorporation of activated platelets into the tangled mass of sickled red cells causing the vaso-occlusion. It illustrates that one possible way forward in sickle cell, is to think of using a combination of therapies, each of which on their own only has a relatively modest effect, but when taken together have a much bigger, clinically useful benefit. I think the next step in this story is to prove the clinical benefit of anti-platelet treatment on pain and then to consider combination therapy.

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