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The spleen was thought in ancient times to be the seat of emotions but its real function, in immunity and to remove time-expired blood cells and circulating microbes, has only been gradually recognised, explains Professor Timothy Cox.
Because the spleen contains macrophages it is almost invariably involved in the course of Gauchers disease when its normal function becomes exaggerated so destroying formed elements of the blood. Macrophages are cells that provide defence against infection by engulfing microbes; they also break down old cells and time-expired proteins within the body.
Many patients with Gauchers disease have had their spleen removed - usually to alleviate the effects of its over-activity but sometimes because it has been ruptured by injury. The spleen is removed for a wide range of conditions besides Gauchers disease and there is long-term experience of the effects of splenectomy (removal of the spleen) as a result.
With an experienced surgeon and good post-operative care, immediate difficulties due to the removal of the spleen are rare. However, beyond surgery, two complications deserve mention: the risks of thrombosis (blood clots) with embolism to the lungs causing severe breathing difficulties; and the risk of overwhelming infection (sepsis or septicaemia).
After the spleen is removed, the number of platelets (minute fragments of blood cells that are essential for normal blood clotting and the prevention of bleeding) usually rises rapidly. This incurs the risk of spontaneous clot formation in the blood vessels and, should these blood clots move to the lungs or elsewhere, there is the risk of embolism.
To a large extent, this complication can be avoided by early mobilisation after surgery, the use of leg bandages during surgery to promote venous flow, the use of short-term injections of the anti-coagulant heparin after splenectomy and taking aspirin which interferes with the action of platelets.
Within a few days of splenectomy, the platelet count usually rises and may reach very high levels for weeks to months afterwards. In many patients, the elevated platelets count persists longer and anti-platelet agents such as aspirin can be considered.
The risk of thrombosis is an important aspect after splenectomy -especially in those who propose to take a holiday abroad and spend many hours immobilised in an aeroplane.
Impairment of immunity
When the spleen has been removed, there is a slight impairment of some aspects of immunity. It has been shown, for example, that the ability of the scavenging phagocytes (macrophages and the circulating white blood cells with similar defensive functions) to ingest foreign proteins and microbes is reduced.
After the spleen is removed, there is little defence against bacterial microbes and this is why the spleen is not normally removed from young children. The risk of overwhelming infection may be as high as 10% in infants; in older children (over the age of 7) the incidence falls to 1%; it is rare but well-known in adults.
After splenectomy there are particular risks from infection with bacteria that have a capsule around them and these are particularly the organism known as the pneumococcus (which is usually implicated in ear infections and pneumonia) and less commonly the meningococcus (which causes meningitis in adults); or the organism Haemophilus influenzae which is implicated in infantile meningitis and other infections, especially of the ear, nose and throat.
Because these organisms make an outer capsule which prevents them from adhering readily to cells that normally engulf and destroy microbes (the polymorphonuclear leucocytes of the blood and macrophages of the tissues), they are virulent, for example a mouse can be killed by as few as 10 encapsulated pneumococci but if the capsule is removed, then many thousands of bacteria can be destroyed before a fatal infection develops.
The spleen with its unique structure that allows concentrated red cells to be delivered to a hugh concentration of macrophages is the main site for clearing these pathogens (disease producing microbes) from the blood. The small number of invading organisms may be sufficient to cause overwhelming sepsis (infection) because the microbes are not percolated through the narrow windows in the micro-circulation of the spleen where they can be attacked.
There is also evidence that the spleen is the site of formation of factors that allow antibodies and complement which are present in the plasma to work together at the surface of phagocytes to promote ingestion of microbes. These factors, as well as the filtering activity of the macrophage system, are reduced when the spleen is damaged or been removed surgically.
Large scale studies indicate that individuals who do not have a spleen are particularly at risk from encapsulated bacteria such as pneumoccoci, meningococci and haemophilus influenzae as well as unusual organisms including the malarial parasite. The protozoan parasites of babesia and malaria cause particularly serious infections in people without spleens. Babesia is like malaria and is transmitted from rodents and cattle by the bite of ticks. A rare bacterium (Bartonella bacilliformis) which is transmitted by the bite of sandflies in the Andean slopes of South America can be particularly severe in patients without a spleen. This organism causes oroya fever, or Carrion's disease, named after the medical student who died whilst finding out its cause.
What can be done about these risks?
It is now not standard practice to carry out therapeutic splenectomy in children for any reason including Gauchers disease until they are at least beyond the age of five and preferably older.
With the advent of bone marrow transplantation for severely affected children with Gauchers disease, as well as enzyme replacement therapy, splenectomy is now much less frequently carried out than in the past.
Avoid travel to tropics
People who have had their spleens removed for Gauchers disease cannot restore their splenic function but they can avoid exposing themselves to some of the organisms that cause serious illness.
I would advise avoiding travel to the tropics where malaria is common (as well as certain infections such as meningitis) and would suggest that young and outward-bound people should avoid travel to the Andean parts of South America as well as the islands of Massachusets where babesiosis is common! Should you need to visit a malarial area, then scrupulous attention to avoiding exposure to mosquitos by the use of insect repellents and mosquito netting is advised. Clearly it is important to take up-to-date and appropriate preventitive medicine should you be bitten by mosquitos that carry malaria.
It is recommended that immunisation with the newer vaccines to many, but not all, strains of pneumococci (Pneumovax II), meningococci (Mengivac (A+C)) and Haemophilus influenzae (the new Hib vaccine) should be given to all patients with Gauchers disease who do not have a spleen and who are over the age of three years. The usual contra-indications to administration of the separate vaccines apply.
It is worth noting also that the Pneumovax should only be given once since sensitivity reactions may follow repeated immunisation. Immunisation with Mengivac may be repeated. The response to these vaccines is not always normal in patients without a functioning spleen and, although there is no evidence that administration of the vaccine before splenectomy is better, it is usual practice to carry out the programme of immunisation before surgery if possible.
Immunisation does not offer complete protection against infection with pneumococci or the other organisms and, should a feverish illness develop after immunisation, infection with these particular organisms should still be considered.
In particular, Mengivac (A+C) gives no protection against meningococcal group B disease that causes local outbreaks in Europe and the vaccination is usually offered to travellers visiting parts of the world where the risk of infection is high, eg the African meningitis belt, parts of the Middle East and the Indian sub-continent.
We do not have categorical proof that immunisation with Mengivac and the new Hib vaccine will give increased benefit to individuals who have had their spleen removed for Gauchers disease and, at the time of writing, the Public Health Laboratory Service has not yet published its guidelines for prevention of sepsis after splenectomy.
However it is already known that the Pneumovax II immunisation gives protection against overwhelming pneumococcal infection which is by far the most common cause of serious sepsis in patients who lack a spleen. It is now standard practice to utilise this for prevention after splenectomy.
Many patients who have had splenectomy for Gauchers disease as children in the past may not have been immunised with this but I would certainly recommend you to get immunised if this is the case. Many bacteriologists, however, feel that in addition to the use of Pneumovax II, immunisation with Mengivac and the new Hib vaccine should be advised in individuals with no spleen .
Other preventitive measures
There are no firm guidelines here except for children where it is recommended universally that children who lack a spleen or in whom the spleen is unable to work properly, prophylactic antibiotics (for prevention of infection) are taken daily: a small dose of soluble penicillin is taken by mouth by those who do not have penicillin allergy. Trial evidence indicates that this greatly reduces the incidence of overwhelming sepsis from organisms such as the pneumococcus and it seems to do this by preventing the organism invading the body.
Many doctors, particularly haemotologists, believe that adults should also take prophylactic penicillin for life. I myself subscribe to this view since in non-allergic individuals, penicillin is cheap and well-tolerated. A small dose of erythromycin can be recommended in those who are allergic to penicillin. At these doses, the drugs cause little inconvenience. They are not broad-spectrum antibiotics, have little long-term toxicity and do not give rise to unpleasant complications such as thrush in those predisposed to get this.
Penicillin or Erythromycin
I recommend either Penicillin V (phenoxymethyl penicillin) 125mgs twice daily or Erythromycin 250 mgs twice daily for those allergic to penicillin. Penicillin does not prevent infection from Haemophilus influenzae where the only orally active agent that can be conveniently given is Amoxicillin. About 10% of Haemophilus influenzae is now resistant to Amoxicillin and moreover this is a broad-spectrum antibiotic that may provoke troublesome thrush, especially in women.
We know from extensive experience and many reports that patients who have had their spleens removed for any reason are at a particular risk from developing overwhelming infection. It is also known that the spleen plays a special role in containing infections acquired usually outside this country eg malaria. In the vast majority of cases, overwhelming infection is due to the pneumococcus which is usually a penicillin-sensitive organism.
Trials in large series of persons whose spleen does not work properly have shown the benefits of immunisation with the vaccine Pneumovax II which gives substantial protection against pneumococcal sepsis. Further trials conducted in children in whom the spleen does not work have shown the benefits of prophylactic penicillin by mouth in relation to sepsis.
Although the efficacy of Mengivac (A+C) and Hib vaccines has been demonstrated in the population at large, they are not yet of proven value after splenectomy. These vaccines, however, have a good safety record and I feel they should also be given to patients with Gauchers disease who have no spleens .
Over the years I have had, like other doctors, experience of patients with-out a spleen who have developed serious bacterial infections, as well as malaria. In some cases, the consequence has been tragic.
I recommend immunisation with all three vaccines provided there are no specific contraindications, avoidance of exposure to organisms such as malaria, and the use of prophylactic penicillin or erythromycin if there is penicillin sensitivity.
Finally I advise that individuals without spleens should be wary of feverish illnesses and consult their doctors promptly. It is most important to realise that even when taking antibiotics and after immunisation, they may still be incubating an infection - one from which they and their doctors believe them to be protected.
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Source: Gauchers News February 1994