Epidemiology & Disease Mechanism
Treatment of WAS
Coping with WAS
One option to improve the platelet counts in patients who are not candidates for transplant is splenectomy, a procedure where the spleen is removed. This organ functions as a "filter" for removing old and abnormal red cells and is a storage site for platelets and white blood cells. The spleen has also an important role in the immune system, by filtering and removing foreign molecules and infectious agents, producing antibodies and providing a site for lymphocyte immune function. In WAS patients the spleen is thought to remove and/or entrap abnormal platelets which has an important role in causing the lower platelet counts and their reduced size.
Patients are hospitalized for a splenectomy and usually require platelet transfusions prior to surgery to keep the counts over 50,000/cu.mm. Platelet transfusions are usually not required after splenectomy. Most often patients are able to go home in a couple of days. In most cases, the effect of splenectomy is almost immediately noticeable with a rise in counts. In one series of 15 cases, most patients (14/15) showed improved platelet counts after splenectomy. However, the lower platelet count recurred intermittently in three of the patiients14.
Advantages of Splenectomy
A splenectomy can reduce the risk of life threatening hemorrhage and can dramatically improve the quality of life in these patients.
A study of 62 patients by Mullen et al12 showed significant improvement in survival in patients who were not transplanted, but underwent splenectomy.
With improvement in platelet counts, children can lead as close a life to normal as possible, including playing sports and active games.
It reduces stress and anxiety for the parents and for the patient.
In patients who have inflammatory diseases (such as arthritis or vasculitis) it improves the quality of life because they can take pain killers such as ibuprofen and other NSAIDS.
In patients undergoing chemotherapy for malignancies the normal platelet counts permits the use of higher dose of chemotherapeutic agents.
This study also indicated that patients with ITP who are splenectomised seem to have a shorter duration of illness and the thrombocytopenia easier to manage.
Disadvantages of Splenectomy
1. There is an increased incidence of life threatening sepsis that has been noticed despite antibiotic prophylaxis.
5/10 patients developed life threatening pneumococcal sepsis/meningitis despite antibiotic prophylaxis(see table below).
In the study by Mullen et al the incidence of fatal sepsis in patients who were on prophylactic antibiotics was 1.2 out of 100 patients per year (which is five times more than the rate for a splenectomized child who does not have WAS).
Preliminary analysis of a recent survey of 182 patients with XLT2 showed that the incidence of serious infections to be 33%(fatal and non fatal sepsis) in the absence of antibiotic prophylaxis. There was a trend towards less severe infectious episodes after splenectomy in patients with antibiotic prophylaxis (16% vs. 33%). However, another study of 15 patients suggested that there was a minimal incidence of sepsis noted when IVIG was given14 along with antibiotic prophylaxis. Most physicians seem to advocate the use of monthly IVIG after splenectomy whereas others do not. Some patients who were on antibiotic prophylaxis have developed sepsis with bacteria that were resistant to the antibiotic. In these patients, the prophylactic antibiotics may have reduced the rapidity of the onset of sepsis. IVIG may be given to prevent infections with bacteria that are resistant to antibiotics and for those few cases where the sepsis is caused by bacteria sensitive to antibiotics.
Table 8..WASP expression and response to therapy
WASP-positive numbers represent WASP detectable by Western blot. WASP-negative numbers represent WASP found absent or truncated by Western blot. — indicates not applicable.
* Good response indicates a platelet count greater than 100 x 109/L; partial response, a platelet count less than 100 x 109/L.
Two patients died of intra cranial hemorrhage, and one died of complications related to BMT.
2. Splenectomy commits these patients to life long antibiotic prophylaxis. Studies have shown that these patients are at a higher risk for sepsis even after a successful transplant15.
3. Splenectomy addresses only one of the issues these patients face ie. bleeding. It does not help prevent the increased incidence of autoimmune complications or malignancy.
4. One study showed that splenectomy prior to transplant increases the mortality rate from sepsis after the transplant15. Even though splenectomized patients have been shown to engraft faster, they appear to be at a higher risk of mortality secondary to infection after transplant.
5. A French study16 showed that patients who had a high level of IgM prior to splenectomy seemed to have a higher rate of development of Autoimmune Hemolytic Anemia. This has not been confirmed in other studies, but it seems prudent to measure IgM levels prior to splenectomy and if it is elevated, discuss the decision further with experts.'
Once considered routine in the management of patients with WAS12 who were not candidates for transplant, splenectomy is losing favor in the treatment of uncomplicated thrombocytopenia in WAS. This is due the increased incidence of serious sepsis noticed in these patients. It could also be due to the significant advances in the field of transplants. Patients with Classic WAS are transplanted. Patients who require more platelet support or develop ITP may be guided onto the transplant pathway as opposed to the splenectomy pathway which addresses only one of the issues faced by these patients. One other factor could be that patients with XLT have lesser number of fatal hemorrhages as compared to patients with Classic WAS. These children are able to live a fairly "normal" life with lower platelet counts and some experts feel that the risk of serious sepsis is more than the risk of a serious bleed. Until experts can concur on what is best for the patients, parents are left, once again, to make these difficult and life altering decisions on behalf of their children.
Patients without a spleen are at risk of overwhelming sepsis. In addition to being vulnerable to infections with bacteria, particularly the encapsulated organisms such as Pneumococcus and Meningococcus, these patients need to be aware that they are more vulnerable to infection after dog bites, tick bites and to malaria. Receiving vaccines, taking antibiotics and IVIG does not protect always protect a patient from sepsis, and there must be a high degree of vigilance that is maintained. If these patient develop a fever of greater than 101o F or 38.3o C, they should be seen at once in the ER to have cultures done and to have antibiotics started. Splenectomized patients may not develop a fever with sepsis and it is important that if they are feeling unwell and uncomfortable, they should be seen at once as this could be sepsis.
Life-long antibiotic prophylaxis is needed with medications such as Pen V twice a day (it may be given once a day if compliance is a problem) or Amoxiciilin once a day or with erythromycin once a day in patients who with penicillin allergies.
All patients should carry an emergency card to alert emergency health personnel about the risk of overwhelming infection. Patients should wear a medical alert bracelet or pendant.
All patient records should be clearly labeled to indicate the risk of infection.
A clear record of all vaccinations and boosters given should be recorded.
Consider recommending patient take a full therapeutic dose of antibiotics if they develop infection symptoms such as fever, malaise, shivering etc. and seek medical advice immediately.
Allowing patients a reserve supply of antibiotics at home or on holiday may also seem appropriate.
All patients with severe WAS should continue on their regular regimen of monthly IVIG after a splenectomy. There is no consensus on whether IVIg is to be given in patients with XLT who have undergone splenectomy. Some physicians advocate this as there have been studies that suggested a decreased incidence of sepsis when IVIG was administered14 along with prophylactic antibiotics. This could be due to the fact that the IVIG could protect the patient against infection with antibioitc resistant organisms or slow the rate of progression of infection.
Please refer to the Immunization Section of this site.
Further Reading on Splenectomy
Further Reading on Splenectomy
Further Reading on Immunization after splenectomy
Further Reading-Platelet Transfusion