Overwhelming post- splenectomy infection

1. Overwhelming post-splenectomy infection • Review splenic structue and function • Effect of splenectomy • OPSI • Evaluating residual splenic function • Alternative approaches • Prevention of OPSI

2. 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

3. 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

4. Splenic function • Hemofiltration • Removal of blood borne organisms • Removal of solid particles from erythrocytes • Destruction of defective or old • Erythrocytes • Platelets • Leukocytes

5. 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

9. Blood enters red pulp and passes through fenestrated epithelium to venous sinus - the flow slows allowing macrophages to perform filtration process

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

11. 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

12. 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

13. 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

14. Splenectomy • Significant decrease in CD4+ T cells-helper cells • Significant decrease in IgM +B cells -memory cells • Related to T-cell independent responses

15. Overwhelming post splenectomy sepsis • First described in 1952 by King and Shumaker-correlating the asplenic state with this rapidly fatal illness

16. 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

17. 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

18. Other possible organisms • E Coli • Capnocytophaga canimorsus (dog bites) • Enterocococcus sp • Group B Streptococci • Bacteroides sp. • Bartonella sp.

19. Other post-splenectomy infections • Susceptible to infections with intraerythrocytic organisms • Protozoal infections • Tick bites-babesiosis Fulminating hemolytic febrile illness • Falciparum malaria Often fatal

21. 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

22. Treatment • Third generation cephalosporin • Cefotaxime or Ceftriaxone • Plus gentamycin • Or Ciprofloxin (for possible urinary or GI source • Or Vancomycin (for possible resistance to penicillin)

23. 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

24. Spleen saving techniques • Splenorrhaphy • Partial splenectomy • Autotransplantation –investigations inconclusive Both result in normal immune function

25. 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

26. Adult data • National trauma data bank • 5 year study on adults • Success 87% among the 90% in which non operative approach was attempted

27. 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

28. Evaluating spleen function • Technetium labeled colloid or rbc scintiscan • Howell-Jolly bodies • Detection of pitted erythrocytes

29. 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

30. 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

31. Calculated 30 ml of implanted splenic tissue necessary to provide some protection • Does not seem to guarantee full protection against OPSI

32. 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

33. 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

34. 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

35. 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

36. PPV-23limitations • Limited persistance of antibodies post-vaccination • Not immunogenic under age 2 • Increasing age • Infection caused by serotype not in vaccine

37. 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

38. PCV-13 • Offers coverage for additional strains • Includes all seven serotypes that are most frequently involved in antibiotic resistance

39. 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

40. Pneumococcal vaccine • >5 years of age through adults • Single dose 14 days post splenectomy • Booster dose at 5 years

41. Conjugating capsular polysaccharides to pneumococcal surface peptides may offer new therapeutic approach in future

42. 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

43. 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

44. 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