Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen

THE PREVENTION AND TREATMENT OF INFECTION IN PATIENTS WITH
AN ABSENT OR DYSFUNCTIONAL SPLEEN

British Committee for Standards in Haematology Guideline up-date

Prepared on behalf of the British Committee for Standards in
Haematology by a Working Party of the Clinical Haematology Task Force.

WORKING PARTY MEMBERS

Dr J Lawton, Consultant in Immunology, St Mary's Hospital, Praed
Street, London, W2 1NY
Dr P G Baddeley, Principal in General Practice, Beacon Medical Practice,
Stepping Stone Lane, Painswick, Stroud,
Gloucestershire, GL6 6RU
Dr A H R Finn, Senior Lecturer in Infectious Disease & Immunology,
Sheffield Children's Hospital, Western Bank,
Sheffield, S10 2TH
Dr R Barnes, Consultant Microbiologist, Department of Microbiology,
University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN
Professor I M Hann, Consultant in Paediatric Haematology, Department of
Haematology, Great Ormond Street Hospital for Children, Great Ormond
Street, London, WC1 3JH
Professor A Burnett, Professor of Haematology, Department of Haematology,
University of Wales Collegeof Medicine, Heath Park, Cardiff, CF14 4XN
Dr J M Davies, Consultant Haematologist, Western General Hospital, Crewe
Road, Edinburgh, EH4 2XU

Address for Correspondence: Dr J M Davies

Consultant Haematologist

Western General Hospital

Crewe Road

EDINBURGH

EH4 2XU

INTRODUCTION

Overwhelming post splenectomy infection remains an area of concern.
The previous BCSH guideline on the prevention and treatment of infection
in patients with an absent or dysfunctional spleen was published in 1996
and significant changes, particularly in vaccine technology, have prompted
a review of the recommendations. A reconvened guideline group chose to
focus on areas of actual or potential change in clinical management,
rather than re-format the original guideline in its entirely. With this
remit the group identified two key areas for consideration, that is
immunisation and antibiotic prophylaxis and treatment.

Methods
The databases, Medline (1996-2000), BIDS Embase (1996-2000) and the
current Cochrane Library
CD-ROM, were searched using the original keywords, infection, splenectomy,
asplenia and hyposplenism. Relevant identified abstracts were reviewed
and cross checked.

Background
No major alteration in the patient categories at risk of infection was
identified. The effect of age and duration of risk appeared similar to
that previously reported, with a broad spectrum of infecting micro-
organisms remaining responsible for serious infections. There may be an
additional risk to splenectomised individuals, in terms of occupational
exposure to certain pathogens.1 This additional risk is at present not
quantifiable. However, in the absence of firm data, on which to base
recommendations, it would seem reasonable to ask both employer and
employees to consider carefully the implications of exposure to
potentially infective biological material.

GUIDELINES (Table 1)

Immunisation
There is no new evidence to suggest that normal inoculations, including
live vaccines, can not be given safely to children or adults with an
absent or dysfunctional spleen.

Pneumococcal Immunisation
The currently available polyvalent pneumococcal vaccine provides a high
degree of immunity in normal subjects. There are well documented failures
of protection in hyposplenic individuals, although the mechanism
underlying this failure is not entirely clear. Despite appropriate
efforts some patients remain unvaccinated, while true vaccine failures may
also contribute to pneumococcal infection post splenectomy.2

Education of both staff and patients as to the risks of post
splenectomy sepsis should continue and the establishment of "At Risk
Registries" may help in this regard. Patients and their relatives should
be aware that despite pneumococcal vaccine and prophylactic antibiotics,
breakthrough pneumococcal infection may occur.3,4

Children under two years of age have an inherently reduced ability to
mount an antibody response to polysaccharide antigens and are, therefore,
at particular risk of vaccine failure. Where splenectomy is unavoidable
under the age of 2 years then a conjugate vaccine (see below) may provide
a more reliable serological response.

New Pneumococcal Vaccines
A seven valent conjugate vaccine has recently completed clinical studies
and should be available for use in late 2000. Early data suggests that
the new conjugate vaccine is more immunogenic but has a more limited
repertoire, in terms of sero-types.5 The seven valent vaccine may have a
future role in primary immunisation of hypo or asplenic patients in tandem
with the currently available vaccine, however, no data specifically
related to asplenic or hyposplenic patients is currently available to
support this approach.

Timing of Vaccination
The current pneumococcal vaccine should be given at least two weeks before
splenectomy. Following splenectomy post vaccination immunoglobulin G,
serum antibody concentrations to pneumococcal antigens do not differ
significantly from normal control subjects, whether vaccination is
undertaken immediately or at 14 days post splenectomy. Functional
antibody responses are, however, better with delayed (14 day) vaccination.
6

All other non-immunised patients at risk should be immunised at the
first opportunity. In general immunisation should be delayed at least
six months after immunosuppressive chemotherapy or radiotherapy.

Re-immunisation of asplenic patients is currently recommended every 5
years. 7 However, it is known that antibody levels may decline more
rapidly, particularly in patients with Sickle cell anaemia and
lymphoproliferative disorders. Decisions on re-immunisation in these
particular circumstances may be made on the basis of antibody levels.

Haemophilus Influenza Type B Immunisation
There is no new data to support an alteration in the recommendations given
in the original guideline. Patients not previously immunised should,
therefore, receive Haemophilus Influenza Type B vaccine. There is no data
to support routine re-immunisation at the present time.

Meningococcal Immunisation
Background
In the United Kingdom there has been a shift in the strains responsible
for Meningococcal infection. Group A strains remain rare and account for
less the 2% of clinical infections. However, Group A strains are epidemic
in other areas of the world. Group B strains now account for 60% of all
isolates, while there has been an increase in Group C strains, which now
contribute 40% of the total. Overall mortality from Meningococcal
infection remains significant, at around 10%.

Meningococcal C Conjugate Vaccine
Immunisations with Meningococcal C conjugate vaccine is now part of the
routine childhood immunisation programme in the UK. The conjugate vaccine
is immunogenic, even in children under two years of age and is likely to
provide long term immunological memory. There is no data specific to
hyposplenic individuals. However, the administration of three doses to
infants and two doses to previously non-immunised children between four
months and twelve months of age would seem appropriate.

In previously non-immunised older children and adults a single dose
of conjugate vaccine is recommended in normal individuals and by extra-
polation should afford protection in hyposplenic or asplenic patients.

The conjugate vaccine is likely to support long standing protection
against Group C Meningococcal disease, in a similar way to the conjugate
Haemophilus Influenza B vaccine. It is, therefore, recommended that
routine Meningococcal immunisation be given pre-splenectomy and for
hyposplenic previously non-immunised individuals. Travellers abroad
should, in addition, receive a Meningococcal vaccine which protects
against Group A infections. There appears to be no contra-indication to
the administration of Meningococcal plain polysaccharide A and C vaccine
to subjects who have previously received Meningococcal C conjugate
vaccine.

Conversely, protection afforded by plain polysaccharide A and C
vaccine is short lived. The immunisation of hyposplenic individuals who
have previously received the plain polysaccharide A and C vaccine with
Meningococcal C conjugate vaccine is, therefore, recommended. Highly
satisfactory serological responses are demonstrable if six months is
allowed between administration of the plain polysaccharide A and C vaccine
and subsequent re-immunisation with Meningococcal C conjugate vaccine.8

Influenza Vaccination
Influenza vaccine continues to be recommended yearly for hypo or asplenic
patients.7

Antibiotic Prophylaxis and Treatment
There are no data to support or refute the previously published
recommendations, as regards antibiotic prophylaxis and treatment of
infection in asplenic individuals. It is accepted, however, that
compliance may be a problem with life long oral antibiotic prophylaxis.8
Overall pneumococcal resistance to penicillins remains low in the United
Kingdom. However, knowledge of local resistant patterns may be used to
guide the choice of chemoprophylactic agents.

RESEARCH AND AUDIT
There is an unmet need for a prospective assessment of serological
response to vaccination in hyposplenic or asplenic patients, particularly
those immunised with the more recently available vaccines. Such
information, if available, would be invaluable in guiding future
vaccination strategies.

Regular audit, quite properly, continues to be undertaken in this
area10. Readily auditable areas include vaccination rates, adherence to
antibiotic prophylaxis and the current outcome of severe infection in
asplenic or hyposplenic patients.

CONCLUSION
Infection in patients with an absent or dysfunctional spleen remains
largely preventable. Preventative strategies continue to be based on
education of staff and patients, appropriate immunisation schedules and
chemoprophylaxis.

REFERENCES

1. Francois B., Gissat V., Moy MC., Vignon P. Recurrent septic shock
due to Streptococcus suis. Journal of Clinical Microbiology 1998; 2395.

2. Waghorn DJ., Mayon-Wight RT. A study of 42 episodes of
overwhelming post splenectomy infection is current guidance in asplenic
individuals being followed. Journal of Infection 1997; 35: 285-294.

3. Shetty N., Aurora P., Ridgway GL. A failure of anti-pneumococcal
vaccine and prophylactic penicillin in the splenectomised patient.
Journal of Infection 1998; 37: 87-88.

4. Klinge J, Hammersen G., Scharf J., Liufficken R., Reinert RR.
Overwhelming post splenectomy infection in vaccine type streptococcus
pneumonie in a 12 year old girl, despite vaccination and antibiotic
prophylaxis. Journal of Infection 1997; 25: 368-371.

5. Chan CY., Molrine DC., George S., Tarbell NJ., Mauch P., Diller
L., Shamberger RC., Phillips NR., Goorin A., Ambrosino DM. Pneumococcal
conjugate vaccine primes for antibody responses to polysaccharide
pneumococcal vaccine after treatment for Hodgkin's disease. Journal of
Infection Disease 1996; 173: 256-258.

6. Shatz DV., Schinskey MF., Pais LB., Romero-Steiner S., Kirton OC.,
Carlone GM. Immune responses of splenectomized trauma patients to the 23-
valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days
after splenectomy The Journal of Trauma, Injury, Infection and Critical
Care 1998; 44: 760-765.

7. Department of Health. Immunisation against infectious disease.
HMSO, London 1992.

8. Department of Health. Immunisation against infectious disease.
HMSO, London 1999.

9. Cummins D., Heuschkel R., Davies SC. Penicillin prophylaxis in
children with Sickle cell disease in Brent. British Medical Journal 1991;
302: 989-990.

10. Pickering J., Campbell H. An audit of the vaccination and
antibiotic prophylaxis practices amongst patients splenectomised in
Lothian. Health Bulletin 2000; 59: 390-395.

KEY GUIDELINES

1. All splenectomised patients and those with functional hyposplenism
should receive pneumococcal immunisation and patients not previously
immunised should receive Haemophilus Influenza Type B vaccine (B,C).
Patients not previously immunised should receive Meningococcal Group C
conjugate vaccine (C). Influenza immunisation should be given (C). Life
long prophylactic antibiotics are still recommended (oral
Phenoxymethylpenicillin or alternative) (B,C).

2. Patients developing infection, despite measures, must be given
systemic antibiotics and admitted urgently to hospital (B,C).

3. Patients should be given written information and carry a card to
alert health professionals to the risk of overwhelming infection.
Patients may wish to invest in an alert bracelet or pendant (C).

4. Patients should be educated as to the potential risks of overseas
travel, particularly with regards malaria and unusual infections, for
example resulting from animal bites (B,C).

5. Patient records should be clearly labelled to indicate the
underlying risk of infection. Vaccination and re-vaccination status
should be clearly and adequately documented (C).

GRADES OF RECOMMENDATIONS

a) Requires at least one randomised controlled trial, as part of the
body of literature of overall good quality and consistency addressing the
specific recommendations.

b) Requires the availability of well conducted clinical studies, but
no randomised clinical trials on topic of recommendation.

c) Requires evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected authorities. Indicates
an absence of a directly applicable clinical studies of good quality.

These grades of recommendations have now been widely adopted, but
originate from the US Agency for Health Care Policy and Research.