SPLENEKTOMİ, OPSI ve KORUNMA STRATEJİLERİ

Yıl 2019, Cilt: 76 Sayı: 1, 109 - 122, 01.03.2019

Umut Gazi Djursun Karasartova Ayşe Semra Güreser

Öz

Vücudun en büyük ikincil bağışıklık organı olan dalağın en önemli görevlerinden bir tanesi kan yoluyla taşınan antijenlere karşı immün cevabı başlatarak kanı yabancı maddelerden temizlemektir. Dalakta kapsüllü mikroorganizmalara saldıran makrofajlar ve erken IgM üretiminden sorumlu B-hücreleri ile birlikte bol miktarda lenfoid doku ve hücre bulunmaktadır. Dalağın yokluğunda, yeni karşılaşılan bir antijene karşı hızlı antikor üretimi bozulur ve bakteriler hızla çoğalır. Post-splenektomik enfeksiyon Overwhelming Post Splenectomy Infection, OPSI mortalitesi yüksek bir hastalıktır. OPSI’nın başlangıç semptomları grip benzeri hastalıklardaki gibi hafif bir seyir izlemesine rağmen, klinik seyir iki gün içinde hızla koma ve ölümle sonuçlanabilir. Dalağı alınmış hastalarda OPSI görülme olasılığı yüksektir ve hastalar bir ömür boyu risk altındadır. OPSI vakaları çoğunlukla Streptococcus pneumoniae S. pneumoniae , Neisseria meningitis N. meningitis ve Haemophilus influenzae H. influenzae kaynaklıdır. Bu yüzden splenektomi yapılmadan en az iki hafta önce, ya da acil splenektomi uygulanacağı durumlarda cerrahi operasyondan en fazla iki hafta sonra pnömokok, meningokok ve Hib aşılaması önerilmektedir. Zaman içerisinde aşılanan bireylerde antikor düzeyinin azalmasından ötürü, splenektomili bireylerin her beş yılda bir yeniden aşılanmaları tavsiye edilir. Öte yandan, OPSI’nın önlenmesinde antibiyotik kullanımının ve hasta eğitiminin de önemli bir yeri vardır. Hastaların OPSI riski ile ilgili bilgilendirilmeleri, özellikle yurt dışı ziyaretleri öncesinde doktorlarına danışmaları gerekmektedir. Bu kadar önemli olmasına rağmen, OPSI riskini azaltmaya yönelik hasta ve hekim eğitimi günümüzde yeterli düzeyde değildir. Bu yüzden, hekimlerin konuya daha duyarlı olmaları ve hastalarının takibini sağlamaları tavsiye edilmektedir. Bu derlememizde dalağı alınmış hastalarda OPSI’nın önlenmesi için kullanılan stratejilerin etkinliği, günümüz literatürü kapsamında, yaptığımız laboratuvar ve klinik çalışmalarını içerecek şekilde tartışılacaktır

Anahtar Kelimeler

Splenektomi, OPSI, aşı, korunma

SPLENECTOMY, OPSI and PREVENTIVE STRATEGIES

Öz

One of the most important functions of the spleen, which is the largest secondary immune system of the body, is to clear blood from foreign substances by initiating an immune response against antigens carried by blood. There are abundant amounts of lymphoid tissue and cells in spleen including macrophages attacking encapsulated microorganisms and B-cells responsible for early IgM production. In the absence of the spleen, rapid antibody production against a newly encountered antigen is impaired and the bacteria can multiply rapidly. Post-splenectomy infection OPSI is a highly mortal disease. Although the initial symptoms of OPSI follow a mild course as in flu-like illnesses, the clinical course can quickly lead to coma and death within two days. Splenectomized patients are susceptible to develop OPSI and possess the risk for lifetime. OPSI cases are mostly caused by Streptococcus pneumoniae S. pneumoniae , Neisseria meningitis N. meningitis and Haemophilus influenzae H. influenzae . Therefore, pneumococcal, meningococcal and Hib vaccination is recommended at least two weeks prior to splenectomy treatment, or at most two weeks after surgery if emergency splenectomy is required. Since the antibody levels decrease in individuals vaccinated over time, splenectomy patients should be re-vaccinated for

Anahtar Kelimeler

Splenectomy, OPSI, vaccination, prevention

Kaynakça

• Morris DH, Bullock FD. the Importance of the Spleen in Resistance To Infection. Ann Surg, ; 70 (5): 513–21.
• Di Sabatino A, Carsetti R, Corazza GR. Post- splenectomy and hyposplenic states. The Lancet, ; 378 (9785): 86-97.
• Pearse G. Normal Structure, Function and Histology of the Thymus. Toxicol Pathol, ; 34 (5): 504–14.
• Rodeghiero F, Ruggeri M. Short- and long-term risks of splenectomy for benign haematological disorders: Should we revisit the indications? Br J Haematol, 2012; 158(1):16-29.
• Kruetzmann S, Rosado MM, Weber H, Germing U, Tournilhac O, Peter H-H, et al. Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J Exp Med Internet, ; 197 (7): 939–45.
• Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, et al. Human blood IgM ‘memory’ B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood, 2004; 104 (12): 3647–54.
• Grönwall C, Vas J, Silverman GJ. Protective roles of natural IgM antibodies. Front in Immunol, ;3:66. doi: 10.3389/fimmu.2012.00066. eCollection 2012.
• Weledji EP. Benefits and risks of splenectomy. Int J Surg, 2014; 12 (2): 113–9.
• King H, Shumacker Jr. HB. Splenic studies. I. Susceptibility to infection after splenectomy performed in infancy. Ann Surg, 1952; 136 (2): –42.
• Skattum J, Naess P a, Gaarder C. Non-operative management and immune function after splenic injury. Br J Surg, 2012; 99 Suppl 1(Suppl 1):59–
• Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect, 2001; 7 (12): –60.
• Okabayashi T, Hanazaki K. Overwhelming postsplenectomy infection syndrome in adults A clinically preventable disease. World J Gastroenterol, 2008; 14 (2): 176–9.
• Sinwar PD. Overwhelming post splenectomy infection syndrome - Review study. Int J Surg, ; 12 (12): 1314–6.
• Wolf HM, Eibl MM, Georgi E, Samstag A, Spatz M, Uranüs S, et al. Long-term decrease of CD4+CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy. Br J Haematol, 1999; 107 (1): –68.
• Karakantza M, Theodorou GL, Mouzaki A, Theodori E, Vagianos C, Maniatis A. In vitro study of the long-term effects of post-traumatic splenectomy on cellular immunity. Scand J Immunol, 2004; 59 (2): 209–19.
• Van Der Laan AM, Ter Horst EN, Delewi R, Begieneman MP V, Krijnen PAJ, Hirsch A, et al. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J, 2014; 35 (6): 376–85.
• Hament JM, Kimpen JL, Fleer a, Wolfs TF. Respiratory viral infection predisposing for bacterial disease: a concise review. FEMS Immunol Med Microbiol, 1999; 26 (3–4): 189–95.
• Landgren O, Björkholm M, Konradsen HB, Söderqvist M, Nilsson B, Gustavsson A, et al. A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin’s lymphoma. J Intern Med, 2004; 255 (6): 664–73.
• Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonisation: The key to pneumococcal disease. Lancet Infect Dis, ; 4 (3): 144–54.
• Goldblatt D, Hussain M, Andrews N, Ashton L, Virta C, Melegaro A, et al. Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study. J Infect Dis, 2005; 192 (3): 387–93.
• Bogaert D, Hermans PW, Adrian P V, Rümke HC, De Groot R. Pneumococcal vaccines: An update on current strategies. Vaccine, 2004; 22(17-18): –20.
• Hoe E, Boelsen LK, Toh ZQ, Sun GW, Koo GC, Balloch A, et al. Reduced IL-17A secretion is associated with high levels of pneumococcal nasopharyngeal carriage in fijian children. PLoS One, 2015; 10(6): e0129199. doi: 10.1371/ journal.pone.0129199.
• Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, et al. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog, 2008; 4 (9): e1000159. doi: 10.1371/ journal.ppat.1000159.
• Zhang Z, Clarke TB, Weiser JN. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest, 2009; 119 (7): 1899–909.
• Marqués JM, Rial A, Muñoz N, Pellay FX, Van Maele L, Léger H, et al. Protection against Streptococcus pneumoniae serotype 1 acute infection shows a signature of Th17- and IFN-γ-mediated immunity. Immunobiology, 2012; 217 (4): 420–9.
• Wright AK, Bangert M, Gritzfeld JF, Ferreira DM, Jambo KC, Wright AD, et al. Experimental human pneumococcal carriage augments IL- A-dependent T-cell defence of the lung. PLoS Pathog, 2013; 9 (3): e1003274. doi: 10.1371/ journal.ppat.1003274.
• Klein Klouwenberg P, Bont L. Neonatal and infantile immune responses to encapsulated bacteria Dev Immunol, 2008;2008:628963. doi: 1155/2008/628963. vaccines. Clin
• Guinamard R, Okigaki M, Schlessinger J, Ravetch J V. Absence of marginal zone B cells in Pyk-2- deficient mice defines their role in the humoral response. Nat Immunol, 2000; 1 (1): 31–6.
• Lane PJ, Gray D, Oldfield S, MacLennan IC. Differences in the recruitment of virgin B cells into antibody responses to thymus-dependent and thymus-independent type-2 antigens. Eur J Immunol, 1986; 16 (12): 1569–75.
• Kraal G, Hart H Ter, Meelhuizen C, Venneker G, Claassen E. Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody. Eur J Immunol, ; 19 (4): 675–80.
• Cameron PU, Jones P, Gorniak M, Dunster K, Paul E, Lewin S, et al. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort. Plos One, 2011; 6 (8): e23164. doi: 10.1371/journal.pone.0023164.
• Pichichero ME. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials. Hum Vaccin Immunother, 2013; 9 (12): 2505–23.
• Bonanni P, Grazzini M, Niccolai G, Paolini D, Varone O, Bartoloni A, et al. Recommended vaccinations for asplenic and hyposplenic adult patients. Hum Vaccin Immunother, 2017; 13 (2); –68.
• No WV, March J, June A. Use of 13-valent pneumococcal conjugate vaccine and valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep , 2013; 62 (25): 521–4. http:// www.ncbi.nlm.nih.gov/pubmed/23803961.
• Giebink GS, Le CT, Cosio FG, Spika JS, Schiffman G. Serum antibody responses of high-risk children and adults to vaccination with capsular polysaccharides of Streptococcus pneumoniae. Rev Infect Dis, 1981; 3 Suppl:S168-78.
• Siber GR, Gorham C, Martin P, Corkery JC, Schiffman G. Antibody response to pretreatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin’s disease. Ann Intern Med, 1986; (4): 467–75.
• Konradsen HB, Rasmussen C, Ejstrud P, Hansen JB. Antibody levels against Streptococcus pneumoniae and Haemophilus influenzae type b in a population of splenectomized individuals with varying vaccination status. Epidemiol Infect, 1997; 119 (2): 167–74.
• Butler JC, Breiman RF, Campbell JF, Lipman HB, Broome C V, Facklam RR. Pneumococcal polysaccharide vaccine efficacy. An evaluation of current recommendations. JAMA, 1993; 270 (15): 1826–31.
• Hosea SW, Burch CG, Brown EJ, Berg RA, Frank MM. Impaired immune response of splenectomized patients to polyvalent pneumococcal vaccine. Lancet, 1981; 11 (8224): 804–7.
• Molrine DC, Siber GR, Samra Y, Shevy DS, MacDonald K, Cieri R, et al. Normal IgG and impaired IgM responses to polysaccharide vaccines in asplenic patients. J Infect Dis, 1999; (2): 513–7.
• Eigenberger K, Sillaber C, Greitbauer M, Herkner H, Wolf H, Graninger W, et al. Antibody responses to pneumococcal and hemophilus vaccinations in splenectomized patients with hematological malignancies or trauma. Wien Klin Wochenschr, ; 119 (7–8): 228–34
• Zorlu M, Karasartova D, Şahiner İ, Güreser AS, Özünel L, Boyacıoğlu İZ, et al. Investigation of antibody levels against Streptococcus pneumoniae and infection risks in splenectomized patients. In: 9th Balkan Congress of Microbiology. 22-24 October 2015. Greece.
• Dagan R, Melamed R, Muallem M, Piglansky L, Greenberg D, Abramson O, et al. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J Infect Dis, ; 174 (6): 1271–8.
• Dagan R, Sikuler-Cohen M, Zamir O, Janco J, Givon-Lavi N, Fraser D. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day- care center attendees. Pediatr Infect Dis J, ; 20 (10): 951–8.
• Obaro SK, Adegbola R, Banya W, Greenwood B. Carriage of pneumococci after pneumococcal vaccination. Lancet, 1996; 348 (9022): 271–2.
• Mbelle N, Huebner RE, Wasas AD, Kimura A, Chang I, Klugman KP. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis, ; 180 (4): 1171–6.
• Herva E, Luotonen J, Timonen M, Sibakov M, Karma P, Mäkelä PH. The effect of polyvalent pneumococcal polysaccharide vaccine on nasopharyngeal and nasal carriage of Streptococcus pneumoniae. Scand J Infect Dis, ; 12 (2): 97–100.
• Klugman PKP, Hayden Smith SW, Koornhof HJ. Evidence that prevention of carriage by pneumococcal capsular vaccines may be the mechanism of protection from pneumococcal pneumonia. South African J Infect Dis, 2011; 26 (4): 221–4.
• Kamboj KK, Kirchner HL, Kimmel R, Greenspan NS, Schreiber JR. Significant variation in serotype-specific immunogenicity of the seven- valent Streptococcus pneumoniae capsular polysaccharide-CRM197 conjugate vaccine occurs despite vigorous T cell help induced by the carrier protein. J Infect Dis, 2003; 187 (10): 1629–38.
• Karasartova D, Gazi U, Tosun O, Gureser AS, Sahiner IT, Dolapci M, et al. Anti-pneumococcal vaccine-induced cellular immune responses in post-traumatic splenectomized individuals. J Clin Immunol, 2017; 37 (4): 388–96.
• Gazi U, Karasartova D, Sahiner IT, Gureser S, Tosun O, Derici KM, et al. The effect of splenectomy on the PCV-13-induced memory B- and T-cell levels. Int J Clin Pract, 2018;e13077. https://doi.org/10.1111/ijcp.13077.
• Melles DC, de Marie S. Prevention of infections in hyposplenic and asplenic patients: An update. Neth J Med, 2004; 62 (2): 45-52.
• Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type b conjugate vaccines. Immunology, 2004; 113 (2): 163–74.
• Granoff DM, Holmes SJ, Osterholm MT, McHugh JE, Lucas AH, Anderson EL, et al. Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines. J Infect Dis, 1993; 168 (3): 663–71.
• Cimaz R, Mensi C, D’Angelo E, Fantola E, Milone V, Biasio LR, et al. Safety and immunogenicity of a conjugate vaccine against Haemophilus influenzae type b in splenectomized and nonsplenectomized patients with Cooley anemia. J Infect Dis, 2001; 183 (12): 1819–21.
• Mikoluc B, Motkowski R, Käyhty H, Heropolitanska- Pliszka E, Pietrucha B, Bernatowska E. Antibody response to Haemophilus influenzae type-b conjugate vaccine in children and young adults with congenital asplenia or after undergoing splenectomy. Eur J Clin Microbiol Infect Dis, ; 31 (5): 805–9.
• Crum-Cianflone N, Sullivan E. Meningococcal vaccinations. Infect Dis Ther, 2016; 5 (2): 89–112.
• Cohn AC, Harrison LH. Meningococcal vaccines: Current issues and future strategies. Drugs, ; 73(11): 1147–55.
• Balmer P, Falconer M, McDonald P, Andrews N, Fuller E, Riley C, et al. Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals. Infect Immun, 2004; 72 (1): 332–7.
• Spoulou V, Tzanakaki G, Lekka S, Chouliaras G, Ladis V, Theodoridou M. Natural and vaccine- induced immunity to Neisseria meningitidis serogroup C in asplenic patients with β-thalassemia. Vaccine, 2011; 29 (27): 4435–8.
• Meerveld-Eggink A, De Weerdt O, De Voer RM, Berbers GAM, Van Velzen-Blad H, Vlaminckx BJ, et al. Impaired antibody response to conjugated meningococcal serogroup C vaccine in asplenic patients. Eur J Clin Microbiol Infect Dis, 2011; (5): 611–8
• Salvadori MI, Price VE. Preventing and treating infections in children with asplenia or hyposplenia. Paediatr Child Health, 2014; 19 (5): –4.
• Harji DP, Jaunoo SS, Mistry P, Nesargikar PN. Immunoprophylaxis in asplenic patients. Int J Surg, 2009; 7(5): 421–3.
• Buzelé R, Barbier L, Sauvanet A, Fantin B. Medical complications following splenectomy. J Visc Surg, 2016; 153(4); 277–86.
• Waghorn DJ. Overwhelming infection in asplenic patients: Current best practice preventive measures are not being followed. J Clin Pathol, ; 54 (3): 214–8.
• Coignard-Biehler H, Lanternier F, Hot A, Salmon D, Berger A, de Montalembert M, et al. Adherence to preventive measures after splenectomy in the hospital setting and in the community. J Infect Public Health, 2011; 4 (4): 187–94.
• Di Carlo I, Primo S, Pulvirenti E, Toro A. Should all splenectomised patients be vaccinated to avoid OPSI? Revisiting an old concept: An Italian retrospective monocentric study. Hepatogastroenterology, 2008; 55 (82–83): 308–
• El-Alfy MS, El-Sayed MH. Overwhelming postsplenectomy infection: is quality of patient knowledge enough for prevention? Hematol J, ; 5 (1): 77–80.
• Butler T. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post- splenectomy infection after dog bites. Eur J Clin Microbiol Infect Dis, 2015; 34 (7): 1271-80.
• Karasartova D, Gureser AS, Zorlu M, Turegun- Atasoy B, Taylan-Ozkan A, Dolapci M. Blastocystosis in post-traumatic splenectomized patients. Parasitol Int, 2016; 65 (6): 802–5.
• Davies JM, Lewis MPN, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PHB. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the Haemato-Oncology Task Force. Br J Haematol, 2011; 155(3): 308–17.
• White K, Covingtom D, Churchill P, Maxwell GJ, Norman KS, Clancy T V. Patient awareness of health precautions after splenectomy. Am J Infect Control, 1991; 19(1): 36–41.
• Zorlu M, Karasartova D, Gureser AS, Sahiner IT, Ozunel L, Boyacı İ, et al. Splenektomili hastalarda pnömokok aşısına karşı oluşan hümoral immunite cevabı ve eğitimin önemi. Ulusal Cerrahi Kongresi 20. 13-17 Nisan 2016. Antalya.Türkiye. h t t p : / / w w w . t i p . h i t i t . e d u . t r / t r / haberler/2015/9/1/splenektomili-dalagi- alinmis-olan-hastalara-egitim-verildi-ve-asi- uygulandi.
• Hegarty P, Tan B, O’Sullivan R, Cronin C, Brady M. Prevention of postsplenectomy sepsis: how much do patients know? Hematol J, 2000;1 (5): –9.
• Ozkan AT, Karasartova D, Gazi U, Gureser AS, Sahiner İT, Derici K, et al. Splenektomili hastalarda pnömokok aşılaması ve aşı etkinliği. In: III Erişkin Aşı Sempozyumu. Nisan 2017. İzmir. Türkiye.
• Ozkoren CS, Pullukcu H, Isıkgoz TM, Sipahi OR, Yamazhan T, Ulusoy S, et al. The rate of pneumococcal vaccination-immunization and knowledge about other vaccines in splenectomized patients. Turkish J Inject, ;21(2):71–4.
• Ulug M, Aslan V, Yilmaz N, Dolu I. An evaluation of immunization practices and their knowledge about this issue in splenectomized patients. Marmara Med. 2014;27:195–8.
• Czerkinsky C, Holmgren J. Topical immunization strategies. Czerkinsky C, Holmgren J. Topical immunization strategies. Mucosal Immunol, ; (3(6): 545–55.
• Schenkel JM, Masopust D. Tissue-resident memory T cells. Immunity, 2014; 41(6): 886–97.
• Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature, 2012; 491 (7424): –7.
• Linterman MA, Hill DL. Can follicular helper T cells be targeted to improve vaccine efficacy? F1000Research, 2016;5 F1000 Faculty Rev-88. doi: 10.12688/f1000research.7388.1.