Absence of the spleen or splenic function predisposes individuals to risk of overwhelming infection. These infections are most often due to encapsulated organisms, especially pneumococcus, Haemophilus influenzae type b, and meningococcus, but any bacterial agent may cause the rapid onset of septicemia, meningitis, pneumonia, and shock characteristic of the asplenic-hyposplenic condition. The risk is greatest in infants and young children, but asplenic-hyposplenic adults also have an increased risk of infection. Prophylactic antibiotics and immunization with polyvalent pneumococcal, H. influenzae type b, and meningococcal vaccines have reduced the incidence of infections in asplenic-hyposplenic individuals, but even these measures have not eliminated the risk. Surgeons have adopted techniques to save as much splenic tissue as possible and some splenic functions, such as pitting red cells, have been preserved, but conservative surgery has not provided total protection against overwhelming infection. Therapies designed to interrupt the cascade of overwhelming sepsis have not yet been successful.
In those cases in which the spleen is surgically removed, the underlying disease or condition leading to splenectomy influences the risk of sepsis. Splenectomy incidental to other operations, such as gastrectomy, results in the lowest risk for overwhelming infection, but this is still some 35-fold greater than the risk for overwhelming infections in the general population. In increasing order of risk, the other main indications for surgical removal of the spleen are idiopathic thrombocytopenia purpura, trauma, transplantation procedures, hereditary spherocytosis, staging Hodgkin's disease, portal hypertension with hypersplenism, and thalassemia. Pathologists should comment on the risk of overwhelming sepsis when spleens are processed as surgical specimens, and should carefully weigh all splenic tissue, including accessory spleens and splenic implants (splenosis), in autopsy cases with and without overwhelming sepsis.
McCluskyDAIII, SkandalakisLJ, ColbornGL, SkandalakisJE. Tribute to a triad: history of splenic anatomy, physiology, and surgery, part 1. World J Surg1999;23:311–325.
2.
MachtDI, FinesilverEM. The effect of splenectomy on integration of muscular movements in the rat. Am J Physiol1922;62:525–530.
3.
MoynihanB.The Spleen and Some of its Diseases. Philadelphia: W.B. Saunders, 1921:4–33.
4.
BuntainWL, LynnHB. Splenorraphy: changing concepts for the traumatized spleen. Surgery1979;86:748–760.
5.
MorgensternL, ShapiroSJ. Techniques of splenic conservation. Arch Surg1979;114:449–454.
6.
PenberthyGC, CooleyTB. Results of splenectomy in childhood. Ann Surg1935;102:645–655.
7.
MayoWJ. The results of splenectomy in the anemias. Ann Surg1919;70:22–29.
8.
MorrisDH, BullockFD. The importance of the spleen in resistance to infectrion. Ann Surg1919;70:513–521.
9.
KingH, ShumackerHBJr.Splenic studies. I. Susceptibility to infection after splenectomy performed in infancy. Ann Surg1952;136:239–242.
10.
FinlandM.Serious infections in splenectomized children. Pediatrics1961;27:689–691.
11.
DiamondLK. Splenectomy in childhood and the hazard of overwhelming infection. Pediatrics1969;43:886–889.
12.
EraklisAJ, KevySV, DiamondLK, GrossRE. Hazard of overwhelming infection after splenectomy in childhood. N Engl J Med1967;276:1225–1229.
13.
BisnoAL, FreemanJC. The syndrome of asplenia pneumococcal sepsis and disseminated intravascular coagulation. Ann Intern Med1970;72:389–393.
14.
BisnoAL. Hyposplenism and overwhelming pneumococcal infection. A reappraisal. Am J Med Sci1971;262:101–107.
15.
BrobergerO, GyulaiF, HirschfeldtJ.Splenectomy in childhood: a clinical and immunological study of forty-two children splenectomized in the years 1951–1958. Acta Paediatr (Upps)1960;49:679–689.
16.
EllisonEC, FabriPJ. Complications of splenectomy. Etiology, prevention and management. Surg Clin North Am1983;63:1313–1330.
17.
LowdenAGR, StewartRHM, WalkerW.Risk of serious infection following splenectomy. BMJ1966;1:446–450.
18.
HodamRP. The risk of splenectomy. A review of 310 cases. Am J Surg1970;119:709–713.
PearsonHA. The spleen and disturbances of splenic function. In: NathanDG, OskiFA, eds. Hematology of Infancy and Childhood, 4th edition. Philadelphia: WB Saunders, 1992:1063–1064.
21.
HooperDC, HoskinDW, GronvikK-O, MurgitaRA. Murine neonatal spleen contains natural T and non-T suppressor cells capable of inhibiting adult alloreactive and newborn autoreactive T-cell proliferation. Cell Immunol1986;99:461–475.
22.
KraalG, Van HoogstratenI, KlerxJPAM, Van DijkH.The selective localization of B lymphocytes in the spleen and the role of complement receptors. Eur J Immunol1985; 15:681–686.
23.
SutliffWD, FinlandM.Antipneumococcic immunity reactions in individuals of different ages. J Exp Med1932; 55:837–852.
24.
FothergillLD, WrightJ.Influenzal meningitis: the relation of age incidence to the bactericidal power of blood against the causal organism. J Immunol1933;24:273–284.
25.
AmlotPL, HayesAE. Impaired human antibody response to the thymus-independent antigen, DNP-ficoll, after splenectomy. Lancet1985;1:1008–1011.
26.
WolfHM, EiblMM, GeorgiE, Long-term decrease of CD4 + CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy. Br J Haematol1999;107:55–68.
27.
ConstantopoulosA, NajjarVA, SmithJW. Tuftsin deficiency: a new syndrome with defective phagocytosis. J Pediatr1972;80:564–572.
28.
HashimotoT, MahourGH, ChurchJA, LipseyAI. Plasma fibronectin levels after splenectomy and splenic autoimplantation in rats with and without dietary ascorbic acid supplementation. J Pediatr Surg1983;18:805–810.
29.
SimonMJr, DjawariD, HohenbergerW.Impairment of polymorphonuclear leukocyte and macrophage functions in splenectomized patients. N Engl J Med1985:1089–1092.
30.
WilcoxLD, DeRoseG, CookeD.Use of the dog spleen for studying effects of irradiation and chemotherapeutic agents, with suggested use of other organs. Cancer1976; 38:62–66.
31.
JandlJH, FilesNM, BarnettSB, MacDonaldRA. Proliferative response of the spleen and liver to hemolysis. J Exp Med1965;122:299–325.
32.
JacobHS. Born again to work again. N Engl J Med1978;298:1415–1416.
33.
KovacsKF, CarideVJ, TouloukianRJ. Regeneration of splenic autotransplants in suckling and adult rats. Arch Surg1981;116:335–336.
34.
SchulkindML, EllisEE, SmithRT. Effect of antibody upon clearance of I125-labelled pneumococci by the spleen and liver. Pediatr Res1967;1:178–184.
ParrilloJE. Mechanisms of disease: pathogenetic mechanisms of septic shock. N Engl J Med1993;328:1471–1477.
37.
FarhiDC, AshfaqR.Splenic pathology after traumatic injury. Am J Clin Pathol1996;105:474–478.
38.
FindlingJW, PohlmannGP, RoseHD. Fulminant gram-negative bacillemia (DF-2) following a dog bite in an asplenic woman. Am J Med1980;68:154–156.
39.
BridgenML, PattulloAL. Prevention and management of overwhelming postsplenectomy infection—an update. Crit Care Med1999;27:836–842.
40.
RichterMN. Spleen, lymph nodes and reticuloendothelial system. In: AndersonWAD. Pathology, 4th ed. St. Louis: C.V. Mosby, 1961:949–950.
41.
SchnitzerB, SodemanTM, MeadML, ContacosPG. An ultrastructural study of the red pulp of the spleen in malaria. Blood1973;41:207–217.
42.
WylerDJ. Splenic functions in malaria. Lymphology1983;16:121–127.
43.
AndersonAE, CassadayPB, HealyGR. Babesiosis in man. Sixth documented case. Am J Clin Pathol1974;62:612–615.
44.
LewisD, PurnellRE, ShawSR, RevingtonJP. The isolation and characterization of human and bovine strains of Babesia divergens from Drumhadrochit, Scotland. Parasitology1980;81:145–155.
45.
RuebushTKII, CassadayPB, MarshHJ, Human babesiosis on Nantucket Island. Ann Intern Med1977;86:6–9.
46.
ArcherGL, ColemanPH, ColeRM, DumaRJ, JohnstonCLJr.Human infection from an unidentified erythrocyte-associated bacterium. N Engl J Med1979;301:897–900.
47.
BernardNF, ChernoffDN, TsoukasCM. Effect of splenectomy on T-cell subsets and plasma HIV viral titers in HIV-infected patients. J Hum Virol1998;1:338–345.
48.
FederHMJr., PearsonHA. Assessment of splenic function in familial asplenia. N Engl J Med1999;341:210–212.
49.
WeissL.The structure of the spleen. In: BeutlerE, LichtmanMA, CollerBS, KippsTJ, eds. Williams Hematology, 5th ed. New York: McGraw-Hill, 1995:38–43.
50.
GastonMH, VerterJI, WoodsG, Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med1986;314:1593–1599.
51.
TorresJ, BisnoAL. Hyposplenism and pneumococcemia. Am J Med1973;55:851–855.
52.
FergusonA.Hazards of hyposplenism. BMJ1982;285:1375–1376.
53.
KalhsP, PanzerS, KletterK, Functional asplenia after bone marrow transplantation: a late complication related to extensive chronic graft-versus-host disease. Ann Intern Med1988;109:461–464.
54.
IvemarkBI. Implications of agenesis of the spleen on the pathogenesis of cono-truncus anomalies in childhood. Acta Paediatr1955;44(Suppl 104):1–110.
55.
RobertsCW, ShutterJR, KorsmeyerSJ. Hox11 controls the genesis of the spleen. Nature1994;368:747–749.
56.
SchillingRF. Estimating the risk for sepsis after splenectomy in hereditary spherocytosis. Ann Intern Med1995; 122:187–188.
57.
Anonymos. Splenectomy for anaemia. Lancet1972;2:367–368.
58.
GrinblatJ, GilboaY.Overwhelming pneumococcal sepsis 25 years after splenectomy. Am J Med Sci1975;270:523–524.
SnellerMC. Clinical features and management. In: StraussSE, moderator. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann Intern Med1999;130:593–595.
64.
InfanteAJ, BrittonHA, DenapoliT, The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a FAS mutation that impairs lymphocyte apoptosis. J Pediatr1998;133:629–633.
65.
LumLG, TubergenDG, CorashL, BlaeseRM. Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome. N Engl J Med1980;302:892–896.
66.
RosnerF, ZarrabiMH. Late infections following splenectomy in Hodgkin's disease. Cancer Invest1983;1:57–65.
67.
Chilcote RR, Baehner RL, Hammond D, and Children's Cancer Study Group.Septicemia and meningitis in children splenectomized for Hodgkin's disease. N Engl J Med1976;295:798–800.
68.
FranckeEL, NeuHC. Postsplenectomy infection. Surg Clin North Am1981;61:135–155.
69.
SchwartzPE, SterioffS, MuchaP, MeltonLJIII, OffordKP. Postsplenectomy sepsis and mortality in adults. JAMA1982;248:2279–2283.
70.
Foss AbrahamsenA, HoibyEA, HannisdalE, Systemic pneumococcal disease after staging splenectomy for Hodgkin's disease 1969–1980 without pneumococcal vaccine protection. Eur J Haematol1997;58:73–77.
71.
FallettaJM, WoodsGM, VerterJI, for the Prophylactic Penicillin Study II. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic penicillin study II. J Pediatr1995;127:685–690.
72.
JugenburgM, HaddockG, FreedmanMH, Ford-JonesL, EinSH. The morbidity and mortality of pediatric splenectomy: does prophylaxis make a difference?J Pediatr Surg1999;34:1064–1067.
73.
MacheskyKK, CushingRD. Overwhelming postsplenectomy infection in a patient with penicillin-resistant Streptococcus pneumoniae. Arch Fam Med1998;7:178–180.
74.
LynnHB. Invited commentary to the overwhelming postsplenectomy sepsis problem. World J Surg1980;4:430–431.
75.
GiebinkGS, LeCT, SchiffmanG.Decline of serum antibody in splenectomized children after vaccination with pneumococcal capsular polysaccharides. J Pediatr1984; 105:576–582.
76.
RubenFL, HankinsWA, ZeiglerZ, Antibody responses to meningococcal polysaccharide vaccine in adults without a spleen. Am J Med1984;76:115–121.
77.
HoseaSW, BurchCG, BrownEJ, BergRA, FrankMM. Impaired response of splenectomized patients to polyvalent pneumococcal vaccine. Lancet1981;1:804–807.
78.
NatansonC.Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med1997;25:1095–1100.
79.
MillerDR, BaehnerRL, MillerLP, eds. Blood Diseases of Infancy and Childhood, 6th ed. St. Louis: C.V. Mosby, 1989:446–447.
WaghornDJ, Mayon-WhiteRT. A study of 42 episodes of overwhelming post-splenectomy infection: is current guidance for asplenic individuals being followed?J Infect1997;35:289–294.
ShiresGT, ThalER, JonesRC, Trauma. In: SchwartzSI, ShiresGT, SpencerFC, eds. Principles of Surgery, 5th ed. New York: McGraw-Hill, 1989;272.
88.
PachterHL, HofstetterSR, SpencerFC. Evolving concepts in splenic surgery: splenorrhaphy vs. splenectomy and postsplenectomy drainage: esperience in 105 patients. Ann Surg1981;194:262–268.
89.
WitteMH, WitteCL, VanWyckDB, FarrellKJ. Preservation of the spleen. Lymphology1983;16:128–137.
90.
GrosfeldJL. Invited commentary to the overwhelming postsplenectomy sepsis problem. World J Surg1980;4:429–430.
91.
GreenJB, ShackfordSR, SiseMJ, PowellRW. Postsplenectomy sepsis in pediatric patients following splenectomy for trauma: a proposal for a multi-institutional study. J Pediatr Surg1986;21:1084–1086.
92.
TraubA, GiebinkGS, SmithC, Splenic reticuloendothelial function after splenectomy, spleen repair, and spleen autotransplantation. N Engl J Med1987;317:1559–1564.
93.
RodgersBM, TribbleC, JoobA.Partial splenectomy for Gaucher's disease. Ann Surg1987;205:693–699.
94.
ZerM, FreudE.Subtotal splenectomy in Gaucher's disease: towards a definition of critical splenic mass. Br J Surg1992;79:742–744.
95.
WadhamBM, AdamsPB, JohnsonMA. Incidence and location of accessory spleens. N Engl J Med1981;304:1111.
96.
RiceHM, JamesPD. Ectopic splenic tissue failed to prevent fatal pneumococcal septicaemia after splenectomy for trauma. Lancet1980;1:565–566.
97.
BuchinoJJ, BuchinoJJ. Thoracic splenosis. South Med J1998;91:1054–1056.
98.
RickertCH, MaasjosthusmannU, Probst-CousinS, AugustC, GullottaF.A unique case of cerebral spleen. Am J Surg Pathol1998;22:894–896.
99.
PearsonH, JohnstonD, SmithKA, TouloukianRJ. The born again spleen: return of splenic function after splenectomy for trauma. N Engl J Med1978;298:1389–1392.
100.
CorazzaGR, TarozziC, VairaD, FrisoniM, GasbarriniG.Return of splenic function after splenectomy: how much tissue is needed?BMJ1984;289:861–864.
101.
OffenbartlK, ChristensenP, GullstrandP, PrellnerK, SegerRA. Treatment of pneumococcal postsplenectomy sepsis in the rat with human gamma globulin. J Surg Res1986;40:198–201.
102.
HiranoT, ForbesSR, RobinsonGT, VelkyTS, GreenburgAG. The effects of heparin and splenectomy on survival and plasma fibronectin levels in rat peritonitis. J Surg Res1986;40:611–616.
103.
AnderssonR, AlwmarkA, BengmarkS.Outcome of pneumococcal challenge in rats after splenic artery ligation or splenectomy. Acta Chir Scand1986;152:15–17.
104.
GhadirianE, KongshavnPAL. The effect of splenectomy on resistance of mice to Entamoeba histolytica infection. Parasite Immunol1985;7:479–487.
105.
JonesTC, AlkanS, ErbP.Murine spleen and lymph node cellular composition and function during cyclophosphamide and splenectomy induced resistance to Toxoplasma gondii. Parasite Immunol1987;9:117–131.
106.
WoodPR, YoungAM, McKimm-BreschkinJL, CheersC.Effect of splenectomy on production of interferon and colony-stimulating factor in Listeria monocytogenes–infected mice. Infect Immun1984;46:860–861.
107.
MadonnaGS, VogelSN. Induction of early-phase endotoxin tolerance in athymic (nude) mice, B-cell-deficient (xid) mice and splenectomized mice. Infect Immun1986; 53:707–710.
