Guideline for the prevention of infection in adult patients following splenectomy or with an absent or dysfunctional spleen

• Summary
• Background
• Diagnosis
• Prophylaxis Recommendations
• Appendix

Summary

Criteria for use of guidelines

• This guideline applies to adult patients who have had a splenectomy or are functionally asplenic who do not have clinical signs of infection
• Patients with symptoms or signs of infection should be rapidly assessed and treated, if necessary, according to severe sepsis guidelines.

Investigations required

• Check allergy status to vaccines and antimicrobial agents.

Antimicrobial Management algorithm

• Following splenectomy, patients are at risk of overwhelming infection. Susceptibility to infection may be greatest in the first few years following splenectomy but persists lifelong.
• Lifelong antibiotic prophylaxis is recommended for patients considered at high risk of pneumococcal infection, i.e. patients age <16 or >50, previous invasive pneumococcal disease, inadequate response to pneumococcal vaccination, patients in the immediate post-operative period after splenectomy for trauma, following splenectomy or splenic radiation for haematological malignancy.
• Compliance with lifelong antibiotics can be a problem so patients not at high risk should be counselled regarding the risks and benefits of lifelong antibiotics and may choose to continue or discontinue prophylaxis
• All patients should receive an emergency supply of Amoxicillin 1g 8-hourly (or Clarithromycin 500mg 12-hourly if penicillin allergic), which should be used immediately if raised temperature, malaise or shivering develops. Patients should also seek immediate medical advice^{2, 4, 9}.  

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Background

Asplenic individuals are at increased risk of life threatening infections^1,2 These infections are often referred to as post splenectomy sepsis (PSS), or overwhelming post splenectomy infection (OPSI). The risk of PSS is highest in children, but increased risk of infection is life long³. Fulminant sepsis has occurred 20-40 years after splenectomy⁴. The relative risk of severe infection in patients that have had a traumatic splenectomy is ten-times greater than in the non-splenectomised population3. The relative risk is 100-fold greater in children and patients with Hodgkin’s disease³.

The mortality from post splenectomy sepsis (PSS) has been predicted to be up to 600 times greater than the general population, with an estimated lifetime risk for post splenectomy sepsis (PSS) being approximately 5%⁵.
Encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are commonly implicated 6. Other important organisms that can cause fulminant post splenectomy sepsis (PSS) include Capnocytophaga canimorsus, Salmonella spp., Escherichia coli and protozoa such as Babesia spp⁷.

This guideline applies to adult patients who have had a splenectomy or are functionally asplenic who do not have clinical signs of infection – patients with symptoms or signs of infection should be rapidly assessed and treated – if necessary according to severe sepsis guidelines.

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Diagnosis

This guideline applies to adult patients who have had a splenectomy and to patient with functional asplenia.
This guideline will not apply to every patient. Discretion should be exerted to modify them accordingly.

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Prophylaxis recommendations

Lifelong antimicrobial prophylaxis is recommended for patients who have had a splenectomy or with functional asplenia and who are considered at high risk of pneumococcal infection. Patients at high risk include those aged <16 or >50, previous invasive pneumococcal disease, inadequate response to pneumococcal vaccination, patients in the immediate post-operative period after splenectomy for trauma, splenectomy or splenic radiation for haematological malignancy)^1,2,7.

Compliance with lifelong antibiotics can be a problem so patients not at high risk should be counselled regarding the risks and benefits of lifelong antibiotics and may choose to continue or discontinue prophylaxis
Recommended regimen: Phenoxymethylpenicillin 250mg 12-hourly orally

• If penicillin allergy: Erythromycin 500mg 12-hourly orally
• If intolerant of both these, a first generation cephalosporin could be considered but the long-term effectiveness or safety is not known
• If a patient becomes nil-by-mouth following a splenectomy, IV benzylpenicillin 1.2g 12-hourly should be given. If patient is allergic to penicillin, Discuss with Microbiology.
  [Evidence level C, D]

Patients who are taking prophylactic antibiotics may require additional antibiotics for intercurrent infection. If the additional antibiotic has a similar or broader spectrum of antimicrobial cover (e.g. cephalosporins, beta-lactams, macrolides or tetracyclins), the prophylactic antibiotic may be interrupted until the course has been completed.

Vaccination is recommended according to table 1 [Evidence level B/C] ^1,2,4,7  

• Prior to elective splenectomy - minimum of 2 weeks before splenectomy.
• Post emergency splenectomy - ideally 14 days post splenectomy.

Table 1. Showing which vaccines and re-immunisation# are required in associated with splenectomy/functional asplenia^{1, 4, 11}.

# Immunisations should be delayed if undergoing chemotherapy, whilst ensuring adequate antibiotic cover is prescribed in the interim.
* If a primary non-responder (pneumococcal Ab titre <30mcg/ml) at 4-6 weeks, give 2 doses of pneumococcal conjugate vaccine (e.g. Prevenar 13®) 2 months apart¹.
** Some medical conditions may cause antibody levels to decline more rapidly e.g. sickle cell anaemia and lymphoproliferative disorders and re-vaccination maybe required more frequently. Decisions on re-immunisation in these particular circumstances may be made on the basis of antibody levels².
Data on long-term antibody levels in individuals with asplenia, splenic dysfunction, immunosuppression or complement deficiency are limited. Additional doses to cover the higher risks of meningococcal and pneumococcal disease during childhood, should be considered, depending on the child’s underlying condition. Specialist advice may be required¹.
##Bexsero® is subject to additional monitoring under black triangle labelling because it is a newly licensed vaccine.
Administration of Vaccines

• Vaccines are routinely given intramuscularly into the upper arm or anterolateral thigh. This is to reduce the risk of localised reactions, which are more common when the vaccine is given subcutaneously. For individuals with a bleeding disorder, however, vaccines should be given by deep subcutaneous injection to reduce the risk of bleeding.
• Side effects of immunisation are usually self-limiting hypersensitivity and pain. These disappear after 48 – 72 hours. Swelling may occur at the site of injection after 24 hours. Less common is fever, malaise, and generalised aches⁸.

Pregnancy / Breast-feeding

• All vaccines within this guideline are inactivated but have limited or no evidence for use in pregnancy and lactation.
• Since inactivated vaccines cannot replicate they cannot cause infection in either the mother or the foetus.
• As asplenic patients are at high risk of infection and sepsis, the benefit of administration of vaccines is generally considered to outweigh the potential risk to the foetus.

Immunosuppressed patients / Chemotherapy

• Immunisations should be delayed. Antibiotic cover should be prescribed in the interim^{4, 8}.
• LHP guidelines for immunisation following haematopoietic stem cell transplantation in adults are available

Educate all patients as to the potential risks of overseas travel especially regarding malaria and unusual infections such as from animal bites.

• Animal Bites
  • All animal bites in splenectomised patients need to be assessed quickly. Capnocytophaga canimorsus can cause severe sepsis in this group of patients and prophylaxis may be required. (Guideline for the management of animal bites). Patients with established soft tissue infections secondary to animal bites should be managed according to cellulitis and soft tissue infection guidelines
• Travelling
  • Asplenic patients should be advised of the increased risk of severe falciparum malaria. Scrupulous adherence to antimalarial prophylaxis is recommended, specialist advice from an infectious disease or tropical disease unit or the local consultant in communicable disease control should be sought. Patients should also take measures to avoid mosquito bites while in an endemic area (e.g. use an insect repellent, mosquito net and cover arms and legs).
  • Patients travelling to endemic areas should receive the MenACWY conjugate vaccine before travelling if >5 years since vaccinated.
  • Patients who are not otherwise taking antibiotic prophylaxis should do so during periods of travel, particularly if travelling “off the beaten track”, and should keep a therapeutic course of Co-Amoxiclav (or Clarithromycin if genuinely penicillin allergic) with them for the duration of the holiday^{4, 8} for use if symptoms of systemic infection develop.
• Tick Bites
  • A third of cases of clinical human babesiosis have occurred⁴ in splenectomised individuals. It is a rare tick borne infection that can cause moderate to severe disease, including haemolytic anaemia. Therefore it is essential to take precautions against being bitten in endemic areas (if camping, cover exposed skin)⁸.

Other Key Recommendations

• Patient records should be clearly labelled to indicate underlying risk of infection including vaccination and re-vaccinations status.
• Patients should be given, and encouraged to carry, a Public Health England patient information leaflet and splenectomy-warning card.
• Patients can also sign up for ‘Medic-Alert’ bracelets free phone 0800 581420).

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Appendix

Vaccine monographs

• PPV= pneumococcal polysaccharide vaccine⁹ http://www.medicines.org.uk/EMC/medicine/1446/SPC/Pneumovax+II/
• Bexsero¹⁰ https://www.medicines.org.uk/emc/product/5168