Abstract
Although patients with cancer and immunosuppression are at a risk of functional hyposplenism, how to detect it promptly remains unclear. Since hyposplenism allows erythrocytes with nuclear remnants (Howell−Jolly bodies [HJBs]) to appear in the peripheral blood, HJB detection by a routine microscopic examination may help identify patients with functional hyposplenism. This prospective study was thus performed to determine the underlying diseases in patients who presented with HJBs. Of 100 consecutive patients presenting with HJBs, 73 had a history of splenectomy. The remaining 27 had hematologic cancer (n = 6, 22%), non-hematologic cancer (n = 8, 30%), hepatic disorders (n = 4, 15%), premature neonates (n = 3, 11%), hemolytic anemia (n = 2, 7%), autoimmune disorders (n = 2, 7%) and miscellaneous diseases (n = 2, 7%), and their prior treatments included chemotherapy (n = 8, 30%), steroids (n = 7, 26%) and molecular-targeted therapy (n = 3, 11%). Among the 27 patients, 22 had computed tomography scans available: 3 (14%) had underlying diseases in the spleen, and the remaining 19 (86%) were all found to have a decreased splenic volume, including 11 (50%) with more than 50% of the ideal value. The present findings suggest that HJB detection identifies patients with potentially functional hyposplenism who should receive appropriate interventional treatment, such as vaccination and prophylactic antibiotics.
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References
Dameshek W. Hyposplenism. JAMA. 1955;157(7):613. https://doi.org/10.1001/jama.1955.02950240051023.
Pearson HA, Spencer RP, Cornelius EA. Functional asplenia in sickle-cell anemia. N Engl J Med. 1969;281(17):923–6. https://doi.org/10.1056/NEJM196910232811703.
Kirkineska L, Perifanis V, Vasiliadis T. Functional hyposplenism. Hippokratia. 2014;18(1):7–11.
Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378(9785):86–97. https://doi.org/10.1016/S0140-6736(10)61493-6.
de Porto AP, Lammers AJ, Bennink RJ, ten Berge IJ, Speelman P, Hoekstra JB. Assessment of splenic function. Eur J Clin Microbiol Infect Dis. 2010;29(12):1465–73. https://doi.org/10.1007/s10096-010-1049-1.
William BM, Corazza GR. Hyposplenism: a comprehensive review. Part I basic concepts and causes. Hematology. 2007;12(1):1–13. https://doi.org/10.1080/10245330600938422.
Sumaraju V, Smith LG. Smith SM (2001) Infectious complications in asplenic hosts. Infect Dis Clin North Am. 2001;15(2):551–65. https://doi.org/10.1016/s0891-5520(05)70159-8.
Johnston SD, Robinson J. Fatal pneumococcal septicaemia in a coeliac patient. Eur J Gastroenterol Hepatol. 1998;10(4):353–4. https://doi.org/10.1097/00042737-199804000-00014.
Rubin LG, Schaffner W. Clinical practice. Care of the asplenic patient. N Engl J Med. 2014;371(4):349–56. https://doi.org/10.1056/nejmcp1314291.
Corazza GR, Ginaldi L, Zoli G, Frisoni M, Lalli G, Gasbarrini G, et al. Howell-Jolly body counting as a measure of splenic function. A reassessment. Clin Lab Haematol. 1990;12(3):269–75. https://doi.org/10.1111/j.1365-2257.1990.tb00037.x.
Corazza GR, Tarozzi C, Vaira D, Frisoni M, Gasbarrini G. Return of splenic function after splenectomy: how much tissue is needed? Br Med J (Clin Res Ed). 1984;289(6449):861–4. https://doi.org/10.1136/bmj.289.6449.861.
Sugawara Y, Hayashi Y, Shigemasa Y, Abe Y, Ohgushi I, Ueno E, et al. Molecular biosensing mechanisms in the spleen for the removal of aged and damaged red cells from the blood circulation. Sensors (Basel). 2010;10(8):7099–121. https://doi.org/10.3390/s100807099.
Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. 2005;5(8):606–16. https://doi.org/10.1038/nri1669.
Inaba T, Ohama A. Prominent increase of Pappenheimer body-containing erythrocytes in a patient with hypoplastic spleen (IJHM-D-18-00279R2). Int J Hematol. 2018;108(4):351–2. https://doi.org/10.1007/s12185-018-2512-5.
Sills RH. Splenic function: physiology and splenic hypofunction. Crit Rev Oncol Hematol. 1987;7(1):1–36. https://doi.org/10.1016/s1040-8428(87)80012-4.
Geraghty EM, Boone JM, McGahan JP, Jain K. Normal organ volume assessment from abdominal CT. Abdom Imaging. 2004;29(4):482–90. https://doi.org/10.1007/s00261-003-0139-2.
Harris A, Kamishima T, Hao HY, Kato F, Omatsu T, Onodera Y, et al. Splenic volume measurements on computed tomography utilizing automatically contouring software and its relationship with age, gender, and anthropometric parameters. Eur J Radiol. 2010;75(1):e97–101. https://doi.org/10.1016/j.ejrad.2009.08.013.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8. https://doi.org/10.1038/bmt.2012.244.
Ong SY, Ng HJ. Howell-Jolly bodies in systemic amyloidosis. Int J Hematol. 2018;108(2):119–20. https://doi.org/10.1007/s12185-018-2473-8.
Boyko WJ, Pratt R, Wass H. Functional hyposplenism, a diagnostic clue in amyloidosis. Report of six cases. Am J Clin Pathol. 1982;77(6):745–8. https://doi.org/10.1093/ajcp/77.6.745.
Cummins KD, Westall GP, Grigoriadis G. Numerous Howell-Jolly bodies in a patient with idiopathic splenic calcification. Br J Haematol. 2015;169(6):767. https://doi.org/10.1111/bjh.13454.
Picardi M, Selleri C, Rotoli B. Spleen sizing by ultrasound scan and risk of pneumococcal infection in patients with chronic GVHD: preliminary observations. Bone Marrow Transpl. 1999;24(2):173–7. https://doi.org/10.1038/sj.bmt.1701861.
Matsubayashi H, Uesaka K, Kanemoto H, Aramaki T, Nakaya Y, Kakushima N, et al. Reduction of splenic volume by steroid therapy in cases with autoimmune pancreatitis. J Gastroenterol. 2013;48(8):942–50. https://doi.org/10.1007/s00535-012-0692-y.
Mbanwi AN, Wang C, Geddes K, Philpott DJ, Watts TH. Irreversible splenic atrophy following chronic LCMV infection is associated with compromised immunity in mice. Eur J Immunol. 2017;47(1):94–106. https://doi.org/10.1002/eji.201646666.
Cerezo-Wallis D, Soengas MS. Understanding Tumor-Antigen Presentation in the New Era of Cancer Immunotherapy. Curr Pharm Des. 2016;22(41):6234–50. https://doi.org/10.2174/1381612822666160826111041.
Burns E, Anand K, Acosta G, Irani M, Chung B, Maiti A, et al. Autosplenectomy in a patient with paroxysmal nocturnal hemoglobinuria (PNH). Case Rep Hematol. 2019;2019:3146965. https://doi.org/10.1155/2019/3146965.
Nores M, Phillips EH, Morgenstern L, Hiatt JR. The clinical spectrum of splenic infarction. Am Surg. 1998;64(2):182–8.
Cull E, Stein BL. Splenic infarction, warm autoimmune hemolytic anemia and antiphospholipid antibodies in a patient with infectious mononucleosis. Int J Hematol. 2012;95(5):573–6. https://doi.org/10.1007/s12185-012-1047-4.
Shubha H, Vivek T. A study of hundred adults cases presenting with normoblastemia. Int J Clin Diagn Pathol. 2019;2:8–13.
Muller AF, Toghill PJ. Splenic function in alcoholic liver disease. Gut. 1992;33(10):1386–9. https://doi.org/10.1136/gut.33.10.1386.
Corazza GR, Addolorato G, Biagi F, Caputo F, Castelli E, Stefanini GF, et al. Splenic function and alcohol addiction. Alcohol Clin Exp Res. 1997;21(2):197–200.
Satapathy SK, Narayan S, Varma N, Dhiman RK, Varma S, Chawla Y. Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non-alcoholic cirrhosis and extrahepatic portal venous obstruction. J Gastroenterol Hepatol. 2001;16(9):1038–43. https://doi.org/10.1046/j.1440-1746.2001.02567.x.
Watzl B, Watson RR. Role of alcohol abuse in nutritional immunosuppression. J Nutr. 1992;122(3 Suppl):733–7. https://doi.org/10.1093/jn/122.suppl_3.733.
Saad AJ, Jerrells TR. Flow cytometric and immunohistochemical evaluation of ethanol-induced changes in splenic and thymic lymphoid cell populations. Alcohol Clin Exp Res. 1991;15(5):796–803. https://doi.org/10.1111/j.1530-0277.1991.tb00603.x.
Stockman JA 3rd, Oski FA. Erythrocytes of the human neonate. Curr Top Hematol. 1978;1:193–232.
Holroyde CP, Oski FA, Gardner FH. The “pocked” erythrocyte. Red-cell surface alterations in reticuloendothelial immaturity of the neonate. N Engl J Med. 1969;281(10):516–20. https://doi.org/10.1056/nejm196909042811002.
Davies JM, Lewis MP, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH, et al. 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. https://doi.org/10.1111/j.1365-2141.2011.08843.x.
Uchino K, Ato F, Yamada S, Matsumura S, Kanasugi J, Nakamura A, et al. Emergence of Howell-Jolly bodies in a patient with splenic hypoplasia complicated by fulminant pneumococcal infection. Rinsho Ketsueki. 2020;61(4):318–21. https://doi.org/10.11406/rinketsu.61.318.
Acknowledgements
We thank all of the members of Department of Clinical Laboratory, Aichi Medical University Hospital for performing routine microscopic examinations and all of the medical staff of Aichi Medical University Hospital who provided valuable assistance in caring for the patients in this study.
Funding
This study was supported by Grants from the Ministry of Education, Culture, Sports and Technology of Japan (#18K08343), the Ministry of Health, Labour and Welfare of Japan, and Sysmex Corporation. The funders played no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.
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AT designed the study and acquired funding. YN collected data in cooperation with ME under the supervision of TN and HT HO and KS evaluated computed tomography scans of the spleen. SM, HY and IH were involved in the management of patients. AT and YN performed the statistical analysis and wrote the paper.
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Explanation of novelty
We capitalized on the fact that Howell-Jolly bodies (HJBs) can be detected by routine clinical microscopy due to hyposplenism, as discovered by Dr. Dameshek, the founder of Blood, when 100 consecutive HJB-positive patients were analyzed, all of whom had underlying splenic diseases or a reduced splenic volume suggestive of functional hyposplenism, except for splenectomized cases. This study is this first to show that the HJB detection can easily and promptly screen patients with potential functional hyposplenism at risk of serious infections, and its usefulness should be recognized again.
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Nakagami, Y., Uchino, K., Okada, H. et al. Potential role of Howell−Jolly bodies in identifying functional hyposplenism: a prospective single-institute study. Int J Hematol 112, 544–552 (2020). https://doi.org/10.1007/s12185-020-02925-7
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DOI: https://doi.org/10.1007/s12185-020-02925-7