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 Pliny was a first century historian

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 Spleen vital-can survive without but performs many important functions

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

Many bacteria first need to be opsonized by complement or spleen produced opsonising molecules Removed efficiently by spleen and liver

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 Still some controversy over their exact role Seem to need the spleen to survive

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 Cohort of children who developed infection after splenectomy caused by encapsulated organisms

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

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%

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 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

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-23 limitations 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

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 Not yet in suggested immunizations

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