ASID Splenectomy Guidelines 2008

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Guidelines for the prevention of sepsis in asplenic andhyposplenic patientsD. Spelman,1 J. Buttery,2 A. Daley,3 D. Isaacs,4,5 I. Jennens,6 A. Kakakios,5 R. Lawrence,7 S. Roberts,8

A. Torda,9

D. A. R. Watson,10

I. Woolley,11,12

T. Anderson13

and A. Street14

on behalf of the AustralasianSociety for Infectious Diseases

1Microbiology and Infectious Diseases, 11Infectious Diseases Unit and 14Haematology Unit, Alfred Hospital, 2Infectious Diseases Unit, Murdoch

Childrens Research Institute, 3Department of Microbiology and Infectious Diseases, Royal Childrens Hospital 6Infectious Diseases Unit, Royal

Melbourne Hospital, and 12Infectious Diseases Unit, Monash Medical Centre, Melbourne, Victoria, 4University of Sydney, 5Childrens Hospital,7Sydney Adventist Hospital and 9Infectious Diseases Unit, University of NSW, Prince of Wales Hospital, Sydney, New South Wales, 10Infectious

Diseases Unit, Canberra Hospital, Canberra, Australian Capital Territory and 13Department of lnfectious Diseases and Microbiology, Royal Hobart

Hospital, Hobart, Tasmania, Australia and 8Department of Microbiology, Auckland City Hospital, Auckland, New Zealand

Key wordsasplenia, hyposplenia, spleen, immunization,

antibiotics.

Correspondence

Denis Spelman, Microbiology and

Infectious Diseases, Alfred Hospital,

Commercial Road, Melbourne,

Vic 3004, Australia.

Email: [email protected]

Received 13 June 2007; accepted 18

October 2007

doi:10.1111/j.1445-5994.2007.01579.x

Abstract

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has

a mortality of up to 50%. The spectrum of causative organisms is evolving as are

recommended preventive strategies, which include education, prophylactic and

standby antibiotics, preventive immunizations, optimal antimalarial advice

when visiting endemic countries and early management of animal bites. How-

ever, there is evidence that adherence to these strategies is poor. Consensus-

updated guidelines have been developed to help Australian and New Zealand

clinicians and patients in the prevention of sepsis in asplenic and hyposplenic

patients.

Introduction

Fulminant sepsis is a riskin patients followingsplenectomy

or in patients who are hyposplenic for other reasons such

as congenital asplenia or coeliac disease or following bone

marrow transplantation.

The incidence of such infections can be reduced by pre-

ventive measures, although compliance with recommen-

dations in the published works is poor.1,2 In this paper, we

review current published works on preventive measures

and their efficacy and based on that review make recom-

mendations for the prevention of sepsis in asplenic and

hyposplenic patients. For the majority of these recommen-

ded interventions, there are no randomized controlled

studies. Therefore, we have not attempted to rate each

according to the quality of available evidence. These rec-

ommendationsare alsobasedon theconsensusand opinion

of the authors, who are active in the fields of infectious

diseases, paediatrics, immunology and haematology.

There are previously published recommendations from

UK,3 which have been recently updated,4 Canada5 and

Australia6 as well as specific postsplenectomy immuniza-

tion guidelines included in USA7 and Canada8 and

New Zealand9 immunization recommendations. We have

examined these in constructing these guidelines. These

present recommendations target Australian and New

Zealand medical practitioners and include references pub-

lished since the publication of previous recommendations.

Causative organisms

The commonest causative organisms are encapsulated

bacteria especially Streptococcus pneumoniae, which has

caused over 50% of cases in some series.2 OtherFunding: None

Potential conflicts of interest: None

Internal Medicine Journal 38 (2008) 349356

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Journal compilation 2008 Royal Australasian College of Physicians 349


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encapsulated bacteria implicated include Neisseria menin-

gitidis2 and Haemophilus influenzae type b (Hib),10 especially

before the era of routine Hib vaccination. Less commonly

described bacterial causes include Gram-negative rods2

and Streptococcus suis.11 Importantly, the spleen also has

a role in removing Babesia,12 plasmodia13 and Ehrlichia

spp.14

and severe infections with these organisms havebeen reported in asplenic or hyposplenic patients.

Most recently, a new organism, Bordetella holmesii15 has

been described as a cause of sepsis in asplenic patients. The

description of the clinical disease caused by this organism

shows how asplenic and hyposplenic individuals may be

a host group for emerginginfectious diseases andhow the

pattern of disease may not be overwhelming sepsis.16

There are many infections, for example, viral respiratory

tract infections and gastroenteritis, in which the inci-

dence and frequency do not appear to be increased in

this patient group, although no significant study has been

carried out.

Patients at risk

The number of persons with asplenia or hyposplenia in

Australia/New Zealand is unknown. It has been estimated

that there are 50 000 such patients in the UK.2 In one UK

district, it was estimated that the prevalence of persons

following splenectomy was 9.75 per 10 000 population.17

Also a single laboratory study found 1 of 200 of the

population (0.5%) were asplenic on the basis of the pres-

ence of HowellJolly bodies.18

The firmest recommendations on prophylaxis are for

patients who have undergone surgical splenectomy.However, there are other patients who have functional

asplenia/hyposplenia in whom the same preventive rec-

ommendations are indicated. These include some patients

who underwent allogeneic bone marrow transplantation,

especially in the presence of chronic graft versus host

disease,19 those with coeliac disease,20 patients with

haemoglobinopathies, for example, sickle cell anaemia,21

thalassaemia major and systemic lupus erythematosus22

and those with inflammatory bowel disease.23 There is also

a small number of patients with familial/congenital asple-

nia.24 The risk in patients who undergo subtotal splenec-

tomy or significant splenic traumaand in whom thespleen

has been preserved is uncertain.

The presence of HowellJolly bodies on a blood film is

accepted as the usual diagnostic marker of asplenia/hypo-

splenia, although this is a marker of the spleens ability to

remove damaged cells rather than of immunological func-

tion.25 There is evidence that the absence of IgM memory

B cells is a predictor of an individuals impaired immune

response to encapsulated bacteria following splenectomy

and this may become the basis for future assessment.26

Incidence of and mortality in sepsis inasplenic patients

The reported incidence varies with the patient group,

duration of follow up, definitions used and whether the

rate is calculated or estimated. In an Australian study, the

reported incidence was 0.42 per 100 person years.27 Other

estimates are 0.180.42 cases per 100 person years,2

7.16

per 100 person years28 and 2.3 per 100 person years at

risk.29 Another wayof presenting rates is the percentage of

patients who develop sepsis postsplenectomy 3.2%,30

4.4% in children


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Splenic salvage

Maximal efforts should be made to preserve splenic tissue

and therefore splenic function. Salvage techniques that

have been suggested include splenic repair, splenorrhaphy

and the embedding of splenic tissue in the omentum.

Patients at risk, for example, following splenic trauma or

with a disease that predisposes them to asplenia/hypo-

splenia, may be monitored for the appearance of Howell

Jolly bodies and by measurement of IgM memory B cells.

Antibiotic prophylaxis

Phenoxymethylpenicillin prophylaxis has mostoften been

used. The Australian Therapeutic Guidelines: Antibiotic

(2006) recommend, for adults, amoxycillin, 250 mg daily

or phenoxymethylpenicillin, 250 mg, p.o., every 12 h,

and for children under 2 years, amoxycillin, 20 mg/kg,

p.o., daily or phenoxymethylpenicillin 125 mg, p.o.,every

12 h.6 For patients hypersensitive to penicillins, roxithro-

mycin (child 4 mg/kg up to)150 mg,p.o. orerythromycin,

250 mg, p.o., daily (all ages) is recommended. Others

recommend moxifloxacin or cotrimoxazole, basedon local

rates of macrolide resistance.34

The duration of antibiotic prophylaxis is controversial.

The most conservative guidelines3 at present recommend

lifelong antibiotics and there is good evidence that the risk

of sepsis is also lifelong. Nevertheless, recommendations

do have to be refined to the needs and wishes of the

individual patient who may be unwilling or incapable of

taking prophylactic antibiotics for decades. In these

patients, we would recommend at least 2 years of pro-phylactic antibiotics followed by the use of emergency or

standby antibiotics and early presentation to medical care.

Such an approach necessitates a rigorous education pro-

gramme with ongoing reinforcement of the need to pres-

ent early to medical care, theneed to maintain vaccination

status and the need to maintain a supply of up-to-date

antibiotics as an emergency supply. Prophylactic phenoxy-

methylpenicillin or amoxycillin is often recommended

lifelong for those patients with an underlying haemato-

logical condition and/or who have ongoing impaired

immune function.35

The only randomized controlled studies of penicillinprophylaxis have been in children with sickle cell an-

aemia. The first study was carried out in very young chil-

dren aged lessthan3 years,the age group with the highest

incidence of sepsis. It found a 84% reduction in pneumo-

coccal bacteraemia in children receiving penicillin V,

occurring in 2 of 105, as compared to 13 of 110 children

receiving placebo over a mean of 15 months (P =

0.0025).36 A second study randomized 400 children aged

5 years with sickle cell disease to penicillin or placebo

and followed them for a mean of 3.2 years.37 There were

four pneumococcal infections in the placebo group and

two in the penicillin arm, although not statistically signifi-

cant. Their conclusion was that it is safe to stop penicillin

prophylaxis at 5 years in sickle cell disease. However, the

effectof theemergence of thedrug-resistantS. pneumoniae on

the effectiveness of antimicrobial prophylaxis is unknown.More recently, a follow-up study of 318 patients (age:

median 18 years, range 1026) who underwent splen-

ectomy between 1985 and 1997 showed a significant

difference in the occurrence of sepsis in those who took

penicillin (2.7%) and those who did not (10%)

(P < 0.01).10 Failures of antibiotic prophylaxis have been

reported, so patients should be warned that prophylaxis

reduces but does not abolish the risk of sepsis.38

Reserve standby antibiotic supply

These patients should have a reserve or standby antibioticsupply with instructions to take in the event of any sudden

onset of unexplained fever, malaise, chills or other con-

stitutional symptoms, especially when medical review is

not readily accessible. Recommended options for adults

include the following.

1 Amoxycillin, 3 g starting dose followed by 1 g, every

8 h.39

2 Amoxycillin/clavulanate, 500/125 mg, every 8 h.34

3 Cefuroxime, 250 mg, every 12 h.34

4 Moxifloxacin in penicillin allergic patient.34

Immunizations

Pneumococcal immunization

There are currently two vaccines available in Australia

and New Zealand: the 23-valent polysaccharide vaccine

(23vPPV), approved for use in older children and adults,

and the 7-valent pneumococcal conjugate vaccine

(7vPCV) approved for use in children up to 9 years. The

7vPCV is more immunogenic in children, especially those

less than 2 years old. Unlike the 23vPPV, it also provides

T-cell-mediated immune memory, avidity maturation of

elicited antibody, mucosal immunity and herd immu-

nity.40,41 The use of pneumococcal vaccine has been

followed by a decrease in pneumococcalinfection in splen-

ectomized patients when compared with historical con-

trols.42 A follow-up study of 318 patients who had

undergone splenectomy showed a significant difference

in the occurrence of sepsis between patients who had had

pneumococcal polysaccharide vaccine (2.4%) and those

who had not (7.8%), (P < 0.05).10 Failures of polysaccha-

ride pneumococcalvaccine in this patient group have been

reported.38

Prevention of sepsis in an a/hyposplenia

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vaccine and immune responses are generally of low titre

and wane relatively quickly. There are no data on immune

responses to this vaccine in asplenic/hyposplenic patients.

The evidence that meningococcal disease occurs more

frequently in asplenic/hyposplenic patients is limited. Case

series of sepsis in asplenic patients have included small

numbers of cases caused by N. meningitidis.2

Patients with lymphoid tumours who underwent splen-

ectomy and who had received chemotherapy or radio-

therapy responded poorly to GpA and GpC meningococcal

vaccines, whereas similar asplenic patients with non-

lymphoid tumours had nearly as good a response as

normal subjects.51 Antibody response to meningococcal

serogroup C conjugate vaccine has also been studied after

splenectomy. The geometric mean titre of bactericidal

antibody was significantly lowerin the splenectomy group

compared with controls.52

We recommend that for an asplenic/hyposplenic Aus-

tralian patient over the age of 12 months and who has not

previously received meningococcal vaccine, a single dose

of MenCCV should be given, followed 68 weeks later by

a single dose of 4vMenPv.43 Infants 06 months old

require two doses of MenCCV, 12 months apart followed

by a further dose at 12 months, and vaccination with

4vMenPV should occur at 2 years of age. Adults and

children over the age of 2 years in New Zealand with

asplenia/hyposplenia should receive a dose of the

4vMenPV.9 For adults and older children in Australia

and New Zealand reimmunization with 4vMenPv is rec-

ommended after 35 years in those with ongoing risk.

New Zealand patients (children) should be given three

doses of MeNZB at intervals of 46 weeks.9,43

The need forrevaccination at 2 years is unclear. It is not a current

recommendation in New Zealand that children with asple-

nia/hyposplenia receive MenCCV.

Asplenic and hyposplenic patients travelling to high-risk

regions of the world should receive the 4vMenPv regard-

less of having received the MenCCV previously.4

Hib immunization

Hib vaccination is recommended for both children and

adults. Children who have received all scheduled vaccine

doses do not require a booster dose following splenec-

tomy.43 Previously unvaccinated adults, especially those

have who have close contact with young children, should

receive a single dose of Hib vaccine.43

Hib vaccine has been shown to be immunogenic in

patients following splenectomy,53 although the immune

response was significantly reduced compared with normal

controls,54 and antibody levels declined more rapidly in

splenectomized patients. The need for revaccination is

uncertain.

Influenza immunization

This is recommended annually for asplenic/hyposplenic

patients over 6 months of age. This may be of benefit in

that prevention of influenza may decrease the risk of

secondary bacterial infection, including pneumococcal

infection.4

Further strategies

Alerts

The medical history should be markedwith an alert sticker

anda checklist shouldbe included in that history outlining

date, type, dose of vaccines andwhen thenext vaccination

is due.

Anatomical pathologists should include a comment on

their histologyreports on therisk of fulminantsepsis when

a spleen is processed, as should a haematologist when

HowellJolly bodies are seen.

Malaria

Due to the increased risk of severe malaria, asplenic and

hyposplenic travellers to endemic areas should be warned

ofthis risk, which shouldbe considered when makingtheir

decision to go and planning their actual itinerary.55

Travellers should take optimal precautions to prevent

infection by means of antimalarial prophylaxis, mosquito

repellents and other barrier precautions. Advice from an

infectious disease physician or expert travel advisor is

recommended.

Babesiosis

This is an unusual infection transmitted by ticks and has

notbeendescribed in Australiaor NewZealand. Thespleen

is an important organ forremoving Babesia spp., which has

produced fatal infections in asplenic patients.56 Travellers

to at risk regions should be warned of this risk.

Meningococcal immunizations for travellers

Travellers with asplenia or hyposplenia should also con-

siderthe quadrivalent vaccine when travellingto high-risk

areas, forexample, sub-Saharan Africa, regardless of them

previously receiving MenCCV.

Animal bites

There is an increased risk of severe sepsis in patients

with asplenia or hyposplenia who are bitten by dogs

and other animals. The common causative organism is


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Capnocytophaga canimorsus. Such patients should be

warned of this risk and have adequate antibiotic cover

following such bites, for example, amoxycillin/clavulanic

acid for 5 days.

Asplenic registry

Registries of patients with asplenia and hyposplenia have

been both reported and recommended.2,57 The potential

role of such ongoing registries is to ensure that patients

(and their carers) are given optimal and up-to-date pre-

ventive advice and that they receive long-term ongoing

support, such as reminders when revaccinations are due.

A registry will also collect important long-term data and

may be the vehicle for studies on the efficacy of recom-

mended interventions.

Summary of recommendations

Educationl All patients and their families should be educated about

the potential risks of fulminant sepsis.

l All should be given written information by their doctor

and encouraged to carry a MediAlert.

l Good communication is necessary with other medical

carers, especially general practitioners.

l Patients who are asplenic or hyposplenic should

promptly report any unexplained fever, chills or consti-

tutional symptoms to their doctor or hospital emergency

department.

Antibiotic prophylaxisl Oral phenoxymethylpenicillin or amoxycillin.

For children aged 18 months and not previously vaccinated.

Number of doses according to age for children.

l Annual influenza immunization

Travel advicel Travellers should be educated and take optimal prevent-

ive measures for the prevention of malaria and babesiosis.

l Travellers to high-risk areas, for example, sub-Saharan

Africa, should have 4vMenPV, regardless of previous

receipt of MenCCV.

Other advicel All persons with asplenia or hyposplenia should be

warned of the risk of animal bites and have early and

optimal treatment of such bites.

l Medical histories should be marked with an alert or

asplenia sticker

Splenic salvage and monitoringl Maximal efforts should be made to preserve splenic

tissue, for example, with splenic embolization rather than

removal of bleeding spleen.

l Patients at risk of hyposplenia may be monitored using

HowellJolly bodies and measurement of IgM memory

B cells.

Acknowledgements

We thank the members of the Australasian Society for

Infectious Diseases, Dr John Andrew from the Royal

College of Pathologistsof Australasia and Mr George Kiroff

from the Royal Australasian College of Surgeons for their

helpful comments.

Spelman et al.

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