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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
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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 Pliny was a first century historian
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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
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Splenic function Hemofiltration Removal of blood borne organisms
Removal of solid particles from erythrocytes Destruction of defective or old Erythrocytes Platelets Leukocytes Spleen vital-can survive without but performs many important functions
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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
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Blood enters red pulp and passes through fenestrated epithelium to venous sinus - the flow slows allowing macrophages to perform filtration process
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Many bacteria first need to be opsonized by complement or spleen produced opsonising molecules
Removed efficiently by spleen and liver
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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
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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 Still some controversy over their exact role Seem to need the spleen to survive
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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
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Splenectomy Significant decrease in CD4+ T cells-helper cells
Significant decrease in IgM + B cells -memory cells Related to T-cell independent responses
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Overwhelming post splenectomy sepsis
First described in 1952 by King and Shumaker-correlating the asplenic state with this rapidly fatal illness Cohort of children who developed infection after splenectomy caused by encapsulated organisms
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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 hours
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OPSI Fulminating sepsis, with meningitis or pneumonia, triggered by bacteria, usually encapsulated organisms Main organisms: S pneumoniae % H influenzae type b N menigitidis Group A Streptococcus
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Other possible organisms
E Coli Capnocytophaga canimorsus (dog bites) Enterocococcus sp Group B Streptococci Bacteroides sp. Bartonella sp.
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Other post-splenectomy infections
Susceptible to infections with intraerythrocytic organisms Protozoal infections Tick bites-babesiosis Fulminating hemolytic febrile illness Falciparum malaria Often fatal
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dx Infection rate Death rate Thalassemia maj 8.2 % 5.1% Sickle cell 7.3 % 4.8% Hodgkin’s 4.1% 1.9% Spherocytosis 3.1% 1.3% ITP 2.1% 1.2% Trauma 2.3 1.1%
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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
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Treatment Third generation cephalosporin Plus gentamycin
Cefotaxime or Ceftriaxone Plus gentamycin Or Ciprofloxin (for possible urinary or GI source Or Vancomycin (for possible resistance to penicillin) Usual source not always identified, includes meningitis or pneumonia in 50% of patients otherwise thought to be nasopharyngeal origin
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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
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Spleen saving techniques
Splenorrhaphy Partial splenectomy Autotransplantation –investigations inconclusive Both result in normal immune function
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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
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Adult data National trauma data bank 5 year study on adults
Success 87% among the 90% in which non operative approach was attempted
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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
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Evaluating spleen function
Technetium labeled colloid or rbc scintiscan Howell-Jolly bodies Detection of pitted erythrocytes
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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
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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
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Calculated 30 ml of implanted splenic tissue necessary to provide some protection
Does not seem to guarantee full protection against OPSI
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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
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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
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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
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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
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PPV-23 limitations Limited persistance of antibodies post-vaccination
Not immunogenic under age 2 Increasing age Infection caused by serotype not in vaccine
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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
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PCV-13 Offers coverage for additional strains
Includes all seven serotypes that are most frequently involved in antibiotic resistance
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Pneumoccal vaccine Children less than 2 years – receive
normal immunization schedule PCV-7 at 2,4,6, and 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
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Pneumococcal vaccine >5 years of age through adults
Single dose 14 days post splenectomy Booster dose at 5 years
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Conjugating capsular polysaccharides to pneumococcal surface peptides may offer new therapeutic approach in future
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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
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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 Not yet in suggested immunizations
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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
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