Infections in Asplenic Patients

EPIDEMIOLOGY OF SPLENECTOMY(Table -1)

  • Aiming at prevention of PSS, the indications for splenectomy have been reassessed.
  • This has resulted in an increasingly conservative approach toward resection and greater efforts to preserve splenic tissue.
  • A variety of splenic salvage procedures are being performed in trauma cases, and splenectomy is no longer a usual procedure in Hodgkin's disease.
  • The procedure remains significant in the management of patients with hereditary hemolytic anemias, spherocytosis.

TABLE -1 Conditions That Are Associated with Need for Splenectomy
  • Trauma

  • Hypersplenism

  • Incidental surgical

  • Portal hypertension

  • Immunologic conditions

- Type 1 Gaucher's disease
- Idiopathic thrombocytopenic purpura
- Thalassemia
- Autoimmune hemolytic anemia
  • Malignancy

- Hodgkin's disease
- Hairy cell leukemia

NONSURGICAL EQUIVALENTS OF SPLENECTOMY

Congenital Asplenia

  • Splenic absence can be congenital rather than surgically acquired.
  • In infants, asplenia usually is linked to serious organ malformations (Ivemark's syndrome).
  • Isolated congenital asplenia diagnosed in adults can occur.

Functional Hyposplenism (Table -2)

  • Mechanisms responsible for splenic dysfunction are:
  • Repeated infarction.
  • Infiltration.
  • Intrasplenic redistribution of blood flow.
  • Antigen-antibody complex blockade.
  • Functional hyposplenism may be partially reversible, as shown by:
  • Improved splenic function in celiac disease with the use of a gluten-free diet.
  • Alcohol abstinence has improved splenic activity in ethanol abusers.
  • Transient splenic dysfunction has been described as occurring secondary to pneumococcemia, perhaps a consequence of low fibronectin levels.

TABLE -2 Conditions That Are Associated with Functional Hyposplenism
Hepatic disorders / Biliary cirrhosis
Chronic active hepatitis
Infiltrative diseases / Amyloidosis
Intestinal disorders / Celiac disease
Intestinal lymphangiectasis
Ulcerative colitis
Crohn's disease
Whipple's disease
Hematologic diseases / Sickle cell hemoglobinopathies
S-beta thalassemia
Essential thrombocythemia
Hemophilia
Collagen vascular diseases / Rheumatoid arthritis
Sjogren's syndrome
Systemic lupus erythematosus
Vasculitis
Endocrine diseases / Grave's disease
Hashimoto's thyroiditis
Hypopituitarism
Neoplasias / Non-Hodgkin's lymphoma
Chronic myelogenous leukemia
Hemangiosarcoma of the spleen
Breast carcinoma
Age / Elderly (>70 y)
Neonates, premature infant
Iatrogenic / Bone marrow transplantation
Graft-versus-host reaction
Parenteral nutrition (chronic)
Splenic irradiation
Thoratrast
Miscellaneous / Sarcoidosis
Fanconi's syndrome
Alcoholism
Dermatitis herpetiformis
Sezary's syndrome
Thrombosis of splenic vessels

Immunologic Functions of the Spleen(Table -3)

TABLE -3 Immunologic Functions of the Spleen
Immune regulatory activities /
  • Development of B- and T-cell memories
  • Maturation of T-suppressor cells
  • Termination of autoantibody production
  • Regulation of idiotype-antiidiotype network

Immune clearance
  • Opsonization
/
  • Production of specific antibody
  • Production of complement
  • Production of tuftsin (tetrapeptide phagocytic adjuvant)

  • Phagocytosis
/
  • Removal of circulating microorganisms
  • Uptake of immune complexes
  • Disposal of senescent cells

Immune surveillance /
  • Delivery of antigenic information
  • B- and T-cell trafficking

ASSESSMENT OF SPLENIC FUNCTION

  • Howell-Jolly bodies (nuclear remnants) and/or "pocked" RBCs are measures of decreased splenic clearance that are used to assess hyposplenic states.
  • The presence of Howell-Jolly bodies has been used as a simple screening test for asplenia, but it is relatively insensitive in the hyposplenic patient without severe impairment of function.
  • Clearance of chromium-tagged heat-damaged RBCs is more sensitive, but this test is invasive and is less available.
  • The "pocked" RBC count (pit count) is a more sensitive indicator of splenic clearance, with RBCs vacuoles visualized by interference phase microscopy.

CLINICAL CHARACTERISTICS OF POSTSPLENECTOMY SEPSIS

Frequency

  • PSS frequency is more variable after children and adult splenectomy, probably because of the more diverse reasons for the procedure.

Timing Related to Splenectomy

  • It is difficult to assess the time for greatest risk after splenectomy.
  • It is generally thought that the risk is highest in the first few years.
  • However, PSS has manifested many years after loss of the spleen, with intervals of more than four decades.

Typical Presentation

  • Short prodrome of low-grade fever with chills, pharyngitis, muscle aches, vomiting, or diarrhea.
  • True rigors are frequently present for 1 to 2 days before clinical deterioration.
  • No clinically demonstrable site of infection is found in adult PSS patients.
  • In children younger than 5 years of age, focal infections, particularly meningitis, are more prominent.
  • The onset of overt deterioration is abrupt, and progression, measured in hours rather than days.
  • Rapid deterioration is often accompanied by disseminated intravascular coagulation, seizures, coma, and cardiovascular collapse.
  • Tissue damage can be compounded by the development of purpura fulminans, in which hypotension, endovascular injury, and coagulopathy contribute to extremity gangrene, resulting in the need for multiple amputations.

Diagnosis

  • Early recognition of PSS must occur so that empiric antimicrobial therapy can be instituted.
  • A high index of clinical suspicion should be maintained for febrile presentations in the splenectomized patient and the patient with a chronic disease that can produce hyposplenism.
  • Bacteremia
  • Bacteria canbe visualized on Gram or Wright staining of the peripheral blood buffy coat.
  • A stained peripheral blood smear can reflect a level of bacteremia of more than 106 /ml, at least 4 logs greater than a usual bacteremia.
  • Gram stain and culture should also be performed on an aspirate of any petechiae or purpurae that have developed.
  • Blood cultures are usually positive within 24 hours and should always be performed to assist in guiding changes in antimicrobial treatment.
  • Cerebrospinal fluid examination may be needed, particularly in children.
  • Examination of the peripheral blood for evidence of malaria or babesiosis may be required.
  • Howell-Jolly bodies or other evidence for hyposplenism should be sought.

Mortality

  • PSS is particularly problematic because of high mortality rates, usually 50 to 70% despite appropriate antimicrobial therapy and intensive medical support.
  • Mortality is generally higher in cases occurring in patients older than 16 years of age, reflecting their somewhat different presentation of illness.

Infectious causes OF POSTSPLENECTOMY SEPSIS

Streptococcus pneumoniae

  • The pneumococcus is the single most important organism implicated in PSS; it is involved in 50 to 90% of cases.
  • Common in all age groups, the percentage of pneumococcal PSS cases tends to increase with age.
  • Lacking the endotoxin of gram-negative organisms, S. pneumoniae can still activate inflammatory cascades leading to disseminated intravascular coagulation and irreversible shock.
  • The mechanism may be related to endovascular injury from the high-grade bacteremia or to direct activation by circulating polysaccharide capsule.
  • Antigen-antibody complexes can also play a role in the activation of complement.

Haemophilus influenzae

  • Type B H. influenzae is the second most common organism related to PSS.
  • Most PSS cases associated with this organism have occurred in children younger than 15 years of age.
  • The use of the conjugated H. influenzae type B vaccine has dramatically decreased the overall incidence of invasive disease.

Neisseria meningitidis

  • Themeningococcus has been cited as the third most common cause of PSS.

Capnocytophaga canimorsus

  • A fastidious gram-negative rod formerly known as CDC group DF-2, is part of the normal oral flora of dogs and cats.
  • It is typically transmitted to humans through contact with an animal, usually a bite or scratch.
  • The finding of gram-negative bacilli in the buffy coat or peripheral blood smear and/or an eschar at the bite site suggests infection by C. canimorsus, which manifests 1 to 7 days after exposure.

Salmonella species

  • Severe infection with this bacillus can be associated with the hyposplenism of chronic reticuloendothelial blockage.
  • Other bacterial organisms
  • Bartonellosis.
  • Nonpneumococcal streptococci.
  • Staphylococcus aureus.
  • Escherichia coli.
  • Campylobacter.
  • Bacteroides.
  • Pseudomonas.
  • Plesiomonas
  • Shigelloides.

RELATION OF SPLENECTOMY TO OTHER INFECTIONS

  • Overall, there is no strong evidence that the asplenic host has a higher frequency or severity of most infections.

Postoperative Period

  • Early postoperative infections after splenectomy are related to pulmonary, urinary, or intra-abdominal sites.
  • In splenectomized trauma patients, both focal infections and bacteremias are more common in patients with additional injuries.
  • The microbiologic causes of these infections are not the usual PSS organisms
  • Staphylococci.
  • Enteric gram-negative bacilli.

Babesiosis and Malaria

  • The asplenic host seems to be more susceptible to more serious infections with certain intra-erythrocytic protozoa.
  • In babesiosis, a significant percentage of the morbidity and mortality in human cases has been found in asplenic hosts.
  • In persons who are partially immune to malaria, the course of Plasmodium falciparum infection was not affected by splenectomy, but parasite clearance was delayed in the nonimmune asplenic patient.

Human Immunodeficiency Virus Infection

  • Splenectomy may be necessary in the treatment of refractory thrombocytopenia in human immunodeficiency virus (HIV) infection and can be associated with PSS.
  • After spleen removal, absolute counts of CD4- and CD8-positive T lymphocyte levels rise.
  • However, the CD4/CD8 ratio remains low and becomes more important in therapeutic decision-making processes for the splenectomized HIV-infected person.

THERAPEUTIC STRATEGIES

Immediate Self-Treatment

  • Because of the potential for fulminant disease, self-administration of antimicrobials at the first sign of a suspicious illness, is a commonly advised practice. Indications for treatment could be fever and rigors or any febrile illness with prostration.

Antimicrobial Interventions

TABLE-5 -- Empiric Postsplenectomy Sepsis Antimicrobial Treatment
Setting / Antimicrobial
Gram-stain evidence of Streptococcus pneumoniae
Areas without concern for penicillin-resistant PRP / Penicillin or ceftriaxone
Areas with concern for moderately resistant PRP (MIC 0.1-1.0 mug/ml) / Ceftriaxone ± vancomycin
Areas with concern for highly resistant PRP (MIC
2.0 mug/ml) / Vancomycin (with or without rifampin) ± ceftriaxone
Gram-stain evidence of a gram-negative bacillus or diplococcus
pseudomonad / Ceftriaxone
ceftazidime
No organism seen on Gram stain / Combination of both approaches
Abbreviations: MIC, Minimal inhibitory concentration; PRP, penicillin-resistant pneumococci.
Adult dosages: penicillin, 4 million units IV every 4 h; ceftriaxone, 2 g IV every 24 h; vancomycin, 1 g IV every 12 h; ceftazidime, 2 g IV every 8 h. These regimens may need modification in patients with renal or hepatic disease. Higher doses of vancomycin may be needed if meningitis is present. Modifications of the regimen chosen should be made when culture and sensitivity data are available.

Potential Immunologic Interventions

  • Because there is a lack or relative lack of opsonizing antibody in the absence of the spleen, intravenous human immunoglobulin (IG) may be useful.
  • The administration of tuftsin, a natural immunomodulating tetrapeptide, can stimulate activity of circulating phagocytes and hepatic Kupffer's cells, helping to compensate for splenic loss.

PREVENTION STRATEGIES

Patient and Family Education

  • Persons without a functioning spleen are more susceptible to certain infections.
  • The infection can be very rapidly progressive and life-threatening.
  • The risk of infection is lifelong, but it is highest in the first year or two after the surgery.
  • All physicians tending the patient should be informed of the condition, no matter how long after the splenectomy.
  • Both vaccination and antimicrobial agents may be used for prevention.

Vaccination

  • Pneumococcal immunization with the polyvalent capsular polysaccharide vaccine is uniformly recommended for the asplenic or hyposplenic host.
  • For elective splenectomy vaccine 2 weeks before the procedure to optimize the antibody response.
  • After emergency splenectomy, immunization is usually given at the time of hospital discharge.
  • Vaccine is poorly immunogenic in children younger than 2 years old.
  • Because specific antibody levels can decrease more rapidly in the asplenic patient, revaccination as frequently as every 2 or 3 years has been suggested.
  • H. influenzae type B conjugated polysaccharide vaccination should also be given to at risk individuals.
  • This vaccine is now part of universal immunization in infants in the developed world, so the target population is asplenics/hyposplenics who are old enough not to have been immunized.
  • Many adults already have specific antibody to this organism, explaining why PSS related to H. influenzae type B has been much less common in adults than in children.
  • Quadrivalent meningococcal vaccine (types A, C, Y and W135) is also immunogenic in asplenic patients but less so in those with diseases treated with chemotherapy and radiotherapy.
  • Yearly influenza vaccination is recommended in the asplenic/hyposplenic patient who falls into the usual high-risk groups for complications of influenza.

Use of Prophylactic Antimicrobials

  • Asplenic pediatric patients oral phenoxymethyl penicillin prophylaxis for the first 2 years of treatment and pneumococcal vaccination.
  • Lifelong prophylaxis in those with underlying immune defects.
  • Asplenic/hyposplenic patients undergoing bacteremia-associated dental procedures.

Spleen-Sparing Treatments

  • Methods of splenic preservation after traumatic rupture are conservative management, splenic repair, and partial splenectomy.
  • Splenosis, growth of peritoneal implants of splenic tissue.

Potential Immunologic Preventive Interventions

  • Granulocyte-macrophage colony-stimulating factor (GM-CSF), used to augment defenses in the neutropenic host.
  • Corynebacterium parvum, a nonspecific adjuvant that stimulates the reticuloendothelial system.

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