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Overwhelming post- splenectomy infection. Review splenic structue and function Effect of splenectomy OPSI Evaluating residual splenic function Alternative approaches Prevention of OPSI. Splenic function. Aristotle postulated that the spleen had no function
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Overwhelming post-splenectomy infection • Review splenic structue and function • Effect of splenectomy • OPSI • Evaluating residual splenic function • Alternative approaches • Prevention of OPSI
Splenic function • Aristotle postulated that the spleen had no function • Pliny proposed that a congested spleen hindered runners and suggested that the asplenic state led to loss of humor and laughter
Splenic function • 16th century Babylonian Talmud suggested that the spleen produced laughter • Maimonedes postulated that the spleen was not responsible for laughter, but purified the blood stream. • Presumably impure blood suppressed laughter
Splenic function • Hemofiltration • Removal of blood borne organisms • Removal of solid particles from erythrocytes • Destruction of defective or old • Erythrocytes • Platelets • Leukocytes
Splenic function • Detects and responds to foreign substances in the blood- lymphocytes responsible for immune activation • Production of antibodies • Production of opsonins-facilitating phagocytosis and complement activation • Storage pool
Blood enters red pulp and passes through fenestrated epithelium to venous sinus - the flow slows allowing macrophages to perform filtration process
Removed efficiently by spleen and liver Many bacteria first need to be opsonized by complement or spleen produced opsonising molecules
Encapsulated organisms • Polysaccharide capsule impedes binding of complement • Can be removed in spleen by natural antibodies produced by IgM memory B cells in marginal zone
IgM positive memory B cells • Can produce natural antibodies against S. pneumoniae, N. menigitidis, and H . Influenze type b and other encapsulated organisms • Can induce immune responses to infection or vaccination • Reduced numbers in children under 2 years of age • Primarily exist in the spleen
Splenectomy • Well known risk for the development of severe bacterial infections • Reflects the spleens ability to remove circulating particulate matter including bacteria • Important role in the initiation of the humoral immune response
Splenectomy • Significant decrease in CD4+ T cells-helper cells • Significant decrease in IgM +B cells -memory cells • Related to T-cell independent responses
Overwhelming post splenectomy sepsis • First described in 1952 by King and Shumaker-correlating the asplenic state with this rapidly fatal illness
OPSI • Medical emergency • Prodrome-fever, chills, myalgia, headache, vomiting, diarrhea • Septic shock-anuria, hypotension, hypoglycemia, DIC, adrenal hemorrhage, multiorgan failure • Mortality rate is 35-80%, usually within first 24-48 hours
OPSI • Fulminating sepsis, with meningitis or pneumonia, triggered by bacteria, usually encapsulated organisms • Main organisms: • S pneumoniae 50-90% • H influenzae type b • N menigitidis • Group A Streptococcus
Other possible organisms • E Coli • Capnocytophaga canimorsus (dog bites) • Enterocococcus sp • Group B Streptococci • Bacteroides sp. • Bartonella sp.
Other post-splenectomy infections • Susceptible to infections with intraerythrocytic organisms • Protozoal infections • Tick bites-babesiosis Fulminating hemolytic febrile illness • Falciparum malaria Often fatal
Incidence of overwhelming infection • Increased in all ages • Most episodes occur within first 2 years • Children at greater risk than adults • Those individuals with splenectomy for hematologic conditions at higher risk • Post traumatic splenectomy less risk may be secondary to splenosis
Treatment • Third generation cephalosporin • Cefotaxime or Ceftriaxone • Plus gentamycin • Or Ciprofloxin (for possible urinary or GI source • Or Vancomycin (for possible resistance to penicillin)
Splenectomy • Increasing awareness of OPSI has led to more conservative approach • guidelines for postraumatic splenectomy is only indicated for patients who are: • Hemodynamically unstable • Have lost more than 1000 cc ‘s of blood • Have required two or more units of PRBC’s • Active and uncontrolled bleeding
Spleen saving techniques • Splenorrhaphy • Partial splenectomy • Autotransplantation –investigations inconclusive Both result in normal immune function
Non-operative management • Upadhyaya and Simpson 1968 • First case controlled study of non operative vs operative management of children with blunt splenic trauma • Results: isolated splenic injuries could be safely treated without surgery in children • Non-operative treatment is now reported to be successful in 90% of isolated splenic injury
Adult data • National trauma data bank • 5 year study on adults • Success 87% among the 90% in which non operative approach was attempted
Non operative management • Conservative management with the use of CT follow up and splenic angiographic embolization for hemorrhage control or treatment of pseudoaneurysms • Studies suggest splenic function preserved
Evaluating spleen function • Technetium labeled colloid or rbc scintiscan • Howell-Jolly bodies • Detection of pitted erythrocytes
Evaluation of spleen function • Measurement of T and B cell subsets • Measurement of post immunization antibody formation • Measurement of IgM anti S pneumoniae response after vaccination is a highly sensitive marker
High frequency of splenosis in children with traumatic splenectomy (59%)with reduction of pitted erythrocytes • Normal levels of pitted erythrocyte counts were found in pts with splenorrhaphy or partial splenectomy • Autotransplantation found to have intermediate levels between normal and splenectomized patients
Calculated 30 ml of implanted splenic tissue necessary to provide some protection • Does not seem to guarantee full protection against OPSI
Prevention • Education • Patients and family should be instructed to notify their physicians of any acute febrile illness especially if associated with rigor or systemic symptoms • Notify physicians of travel to tropical countries – risk of parasitic infections • Notify physicians of any bites • No consensus for dental prophylaxis
Prevention • Antibiotics • Not evidence based • Patients most likely to benefit: • Children under 5 years of age • Individuals who have had splenectomy within the past year • Individuals with underlying immunodeficiency in addition to splenectomy
regimens • Children: < 5 years of age: 125mg BID of Penicillin G • >5 years: 250 mg BID of Penicillin G • Adults : not generally recommended • Alternatives: co-trimoxazole or erythromycin • Episodic short-term antibiotics at the time of febrile illnesses
Vaccinations • PPV-23-productions of opsonising anticapsular antibodies by T-cell-independedt mechanism • Recommended for children older than 5 years • 2 weeks prior to elective surgery • 2 weeks post emergency splenectomy • Revaccination after 5 years
PPV-23limitations • Limited persistance of antibodies post-vaccination • Not immunogenic under age 2 • Increasing age • Infection caused by serotype not in vaccine
PCV-7 • Conjugate of polysaccharide to a protein • More immunogenic • T-lymphocyte dependent response in patients who have immature B cell population • Relevant for patients under 2, or patients who have already undergone splenectomy
PCV-13 • Offers coverage for additional strains • Includes all seven serotypes that are most frequently involved in antibiotic resistance
Pneumoccal vaccine • Children less than 2 years – receive normal immunization schedule • PCV-7 at 2,4,6, and 12-15 months of age • PPV-23 at 2 years of age • Booster in 5 years • Children 2-5 years of age • PCV-7 x2 , 2 months apart followed in 2 months with PPV-23 • Booster in 5 years
Pneumococcal vaccine • >5 years of age through adults • Single dose 14 days post splenectomy • Booster dose at 5 years
Conjugating capsular polysaccharides to pneumococcal surface peptides may offer new therapeutic approach in future
Vaccines • H influenzae type b for adults and children • Conjugated vaccine • <2 years give routine vaccination schedule • >2 years - single vaccination in adults seems to be sufficient
Vaccines • N meningitidis • Conventional tetravalent vaccine - little efficacy under 2-3 years of age (T cell independent) • Conjugate vaccine against serogroup C is highly immunogenic in the first few months of life and also in adults
Better markers to assess splenic function and vaccination response after trauma-(even in patients with non-operative management) might improve risk assessment for overwhelming postsplenectomy infection