Hypersplenism: History and current status

Yunfu Lv, Wan Yee Lau, Yejuan Li, Jie Deng, Xiaoyu Han, Xiaoguang Gong, Ning Liu, Hongfei Wu, Yunfu Lv, Wan Yee Lau, Yejuan Li, Jie Deng, Xiaoyu Han, Xiaoguang Gong, Ning Liu, Hongfei Wu

Abstract

Hypersplenism is a common disorder characterized by an enlarged spleen which causes rapid and premature destruction of blood cells. This review summarizes the history of hypersplenism, discuss its classification and pathogenesis, and examines its diagnosis and treatment options. We performed a comprehensive literature search using PubMed, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) database, reviewed hypersplenism-related articles and summarized the major findings. According to its etiological causes, hypersplenism is characterized by splenomegaly and peripheral cytopenias. It can be classified into three categories: i) primary hypersplenism; ii) secondary hypersplenism; and iii) occult hypersplenism. A number of mechanisms causing hypersplenism have been identified, and mainly involve retention in the spleen, phagocytosis, and autoimmunity. Treatment options for hypersplenism include etiological treatment, non-surgical treatment, total splenectomy and liver transplantation. In any case, treatment should be individualized for each patient.

Keywords: classification; historical review; hypersplenism; pathogenesis; splenectomy; splenomegaly.

References

    1. Kodama T, Takehara T, Hikita H, Shimizu S, Li W, Miyagi T, Hosui A, Tatsumi T, Ishida H, Tadokoro S, et al. Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice. Gastroenterology. 2010;138:2498.e1–2498.e7. doi: 10.1053/j.gastro.2010.02.054.
    1. Hernandez-Gea V, Friedman SL. Platelets arrive at the scene of fibrosis……studies. J Hepatol. 2011;54:1063–1065. doi: 10.1016/j.jhep.2010.10.045.
    1. Djordjević J, Svorcan P, Vrinić D, Dapcević B. Splenomegaly and thrombocytopenia in patients with liver cirrhosis. Vojnosanit Pregl. 2010;67:166–169. doi: 10.2298/VSP1002166D. (In Serbian)
    1. Lv Y, Han X, Gong X, Ma Q, Chang S, Wu H, Li Y, Deng J. Grading of peripheral cytopenias caused by nonalcoholic cirrhotic portal hypertension and its clinical significance. Cell Biochem Biophys. 2015;71:1141–1145. doi: 10.1007/s12013-014-0321-x.
    1. Chauffard M. A'propos de la communication de M. Vaquez. Bull Soc mzed Hop Paris. 1907;24:1201–1203.
    1. Morawitz P, Denecked G. Erkrankungen der Milz. In: von Bergmann G, Staehelin R, editors. Handbuch der inneren Medizin. 2nd. Vol. 4. Springer; Berlin: 1926. pp. 217–236. (In German)
    1. Dameshek W. Hypersplenism. Bull NY Acad Med. 1955;31:113–136.
    1. Lv Y. Causes of peripheral blood cytopenias in patients with liver cirrhosis portal hypertension and clinical significances. Open J Endocr Metab Dis. 2014;4:85–89. doi: 10.4236/ojemd.2014.44010.
    1. Shah SH, Hayes PC, Allan PL, Nicoll J, Finlayson ND. Measurement of spleen size and its relation to hypersplenism and portal hemodynamics in portal hypertension due to hepatic cirrhosis. Am J Gastroenterol. 1996;91:2580–2583.
    1. Aster RH. Pooling of platelets in the spleen: Role in the pathogenesis of ‘hypersplenic’ thrombocytopenia. J Clin Invest. 1966;45:645–657. doi: 10.1172/JCI105380.
    1. Charrier S, Blundell M, Cédrone G, Louache F, Vainchenker W, Thrasher AJ, Galy A. Wiskott-Aldrich syndrome protein- deficient hematopoietic cells can be efficiently mobilized by granulocyte colony-stimulating factor. Haematologica. 2013;98:1300–1308. doi: 10.3324/haematol.2012.077040.
    1. Li ZF, Zhang Y, Gao J, Zhang PJ, Wang JX, Liu XG. Expression and significance of Toll-like receptor 4 of splenic macrophage in patients with hypersplenism due to portal hypertension. Zhonghua Yi Xue Za Zhi. 2004;84:1088–1091. (In Chinese)
    1. Griffith RC, Janney CG. Hematopoiet system: bone marrow and blood, spleen, and lymph nodes. In: Kissane JM, editor. Anderson's Pathology. 9th. Mosby; St. Louis, MO: 1990. pp. 1408–1447.
    1. Jiang A, Zhang S, Li Z, Liang R, Ren S, Li J, Pu Y, Yang J. miR-615-3p promotes the phagocytic capacity of splenic macrophages by targeting ligand-dependent nuclear receptor corepressor in cirrhosis-related portal hypertension. Exp Biol Med (Maywood) 2011;236:672–680. doi: 10.1258/ebm.2011.010349.
    1. Ma S, Li A, Li Z, Zhang S, Jiang A, Zhang J, Zhou R, Dang S. Study of differential expression of cytokines between portal hypertensive hypersplenic tissue and normal splenic tissue by protein array. Chin Arch Gen Surg. 2008;6:455–459. (In Chinese)
    1. Eubank TD, Galloway M, Montague CM, Waldman WJ, Marsh CB. M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. J Immunol. 2003;171:2637–2643. doi: 10.4049/jimmunol.171.5.2637.
    1. Ma J, Chen T, Mandelin J, Ceponis A, Miller NE, Hukkanen M, Ma GF, Konttinen YT. Regulation of macrophage activation. Cell Mol Life Sci. 2003;60:2334–2346. doi: 10.1007/s00018-003-3020-0.
    1. Yamashita U, Kuroda E. Regulation of macrophage-derived chemokine (MDC, CCL22) production. Crit Rev Immunol. 2002;22:105–114. doi: 10.1615/CritRevImmunol.v22.i2.10.
    1. Vulcano M, Albanesi C, Stoppacciaro A, Bagnati R, D'Amico G, Struyf S, Transidico P, Bonecchi R, Del Prete A, Allavena P, et al. Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro and in vivo. Eur J Immunol. 2001;31:812–822. doi: 10.1002/1521-4141(200103)31:3<812::AID-IMMU812>;2-L.
    1. Lin SD, Kawakami T, Ushio A, Sato A, Sato S, Iwai M, Endo R, Takikawa Y, Suzuki K. Ratio of circulating follistatin and activin A reflects the severity of acute liver injury and prognosis in patients with acute liver failure. J Gastroenterol Hepatol. 2006;21:374–380. doi: 10.1111/j.1440-1746.2005.04036.x.
    1. Brugger W, Möcklin W, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L. Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin. Blood. 1993;81:2579–2584.
    1. Yan F, Li W, Chen JT, Zeng YM, Guo YW, Zhang FR, Li ZF. cDNA microarray-based screening of differentially expressed genes in macrophages in the spleen of patients with portal hypertension and hypersplenism. Nan Fang Yi Ke Da Xue Xue Bao. 2006;26:1548–1551. (In Chinese)
    1. Yamada M, Sato N, Taniyama C, Ohtani K, Arai K, Masai H. A 63-base pair DNA segment containing an Sp1 site but not a canonical E2F site can confer growth-dependent and E2F-mediated transcriptional stimulation of the human ASK gene encoding the regulatory subunit for human Cdc7-related kinase. J Biol Chem. 2002;277:27668–27681. doi: 10.1074/jbc.M202884200.
    1. Friedman LS. The risk of surgery in patients with liver disease. Hepatology. 1999;29:1617–1623. doi: 10.1002/hep.510290639.
    1. Kajihara M, Kato S, Okazaki Y, Kawakami Y, Ishii H, Ikeda Y, Kuwana M. A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis. Hepatology. 2003;37:1267–1276. doi: 10.1053/jhep.2003.50209.
    1. Pereira J, Accatino L, Alfaro J, Brahm J, Hidalgo P, Mezzano D. Platelet autoantibodies in patients with chronic liver disease. Am J Hematol. 1995;50:173–178. doi: 10.1002/ajh.2830500305.
    1. Zucker ML, Hagedorn CH, Murphy CA, Stanley S, Reid KJ, Skikne BS. Mechanism of thrombocytopenia in chronic hepatitis C as evaluated by the immature platelet fraction. Int J Lab Hematol. 2012;34:525–532. doi: 10.1111/j.1751-553X.2012.01429.x.
    1. Eissa LA, Gad LS, Rabie AM, El-Gayar AM. Thrombopoietin level in patients with chronic liver diseases. Ann Hepatol. 2008;7:235–244.
    1. Dusheiko G. Thrombopoietin agonists for the treatment of thrombocytopenia in liver disease and hepatitis C. Clin Liver Dis. 2009;13:487–501. doi: 10.1016/j.cld.2009.05.012.
    1. Sanjo A, Satoi J, Ohnishi A, Maruno J, Fukata M, Suzuki N. Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases. J Gastroenterol Hepatol. 2003;18:638–644. doi: 10.1046/j.1440-1746.2003.03026.x.
    1. Rios R, Sangro B, Herrero I, Quiroga J, Prieto J. The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol. 2005;100:1311–1316. doi: 10.1111/j.1572-0241.2005.41543.x.
    1. Lv YF, Li XQ, Gong XG, Xie XH, Han XY, Wang BC. Effect of surgery treatment on hypersplenism caused by cirrhotic portal hypertension. Minerva Chir. 2013;68:409–413.
    1. Jäger A, Kuchroo VK. Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol. 2010;72:173–184. doi: 10.1111/j.1365-3083.2010.02432.x.
    1. Stein SF, Harker LA. Kinetic and functional studies of platelets, fibrinogen, and plasminogen in patients with hepatic cirrhosis. J Lab Clin Med. 1982;99:217–230.
    1. Ikura Y, Ohsawa M, Okada M, Iwai Y, Wakasa K. The significance of platelet consumption in the development of thrombocytopenia in patients with cirrhosis. Am J Med Sci. 2013;346:199–203. doi: 10.1097/MAJ.0b013e31826e364d.
    1. Kalambokis G, Tsianos EV. Endotoxaemia in the pathogenesis of cytopenias in liver cirrhosis Could oral antibiotics raise blood counts? Med Hypotheses. 2011;76:105–109. doi: 10.1016/j.mehy.2010.08.043.
    1. Zuchini R, Huang CH, Tsai HW, Huang SC, Lin CP, Chen CY, Lee GB, Lin XZ. Electromagnetic thermoablation to treat thrombocytopenia in cirrhotic and hypersplenic rats. J Gastroenterol Hepatol. 2010;25:1578–1586. doi: 10.1111/j.1440-1746.2010.06266.x.
    1. Chernykh ER, Starostina NM, Paltsev AI, Leplina OY, Shevela EY, Shipunov MV, Selihova YB, Kulagin AD, Lisukov IA, Nikonov SD, et al. Autologous bone marrow cells in the treatment of cirrhosis of the liver. Bull Exp Biol Med. 2007;144:640–645. doi: 10.1007/s10517-007-0393-3.
    1. Zhang W, Zhang S, Li ZF, Huang C, Ren S, Zhou R, Jiang A, Yang AN. Knockdown of PIK3R1 by shRNA inhibits the activity of the splenic macrophages associated with hypersplenism due to portal hypertension. Pathol Res Pract. 2010;206:760–767. doi: 10.1016/j.prp.2010.07.009.
    1. Kenawi MM, el-Ghamrawi KA, Mohammad AA, Kenawi A, el-Sadek AZ. Splenic irradiation for the treatment of hypersplenism from congestive splenomegaly. Br J Surg. 1997;84:860–861. doi: 10.1046/j.1365-2168.1997.02673.x.
    1. Ismail E, Abdelmoety H, Elgerby MM, Abden H. Splenic irradiation in the treatment of hypersplenism from congestive splenomegaly. Life Sci J. 2012;9:1121–1126.
    1. Feng Kai, Ma K-S, Dong J-H. Acta Academiae Medicinae Militaris Tertiae. Vol. 28. (In Chinese); 2006. Changes of serum Tuftsin content among hypersplenism patients before and after radiofrequency ablation or splenectomy; pp. 1983–1985.
    1. Spigos DG, Jonasson O, Mozes M, Capek V. Partial splenic embolization in the treatment of hypersplenism. AJR Am J Roentgenol. 1979;132:777–782. doi: 10.2214/ajr.132.5.777.
    1. Sankararaman S, Velayuthan S, Vea R, Herbst J. Severe gastric variceal bleeding successfully treated by emergency splenic artery embolization. Pediatr Int. 2013;55:e42–e45. doi: 10.1111/ped.12014.
    1. He XH, Li WT, Peng WJ, Li GD, Wang SP, Xu LC. Total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism. World J Gastroenterol. 2011;17:2953–2957. doi: 10.3748/wjg.v17.i24.2953.
    1. Krishnan SK, Hill A, Hillmen P, Arnold LM, Brooksbank GL, Wood A, Scarsbrook A, Davies MH, Kelly RJ. Improving cytopenia with splenic artery embolization in a patient with paroxysmal nocturnal hemoglobinuria on eculizumab. Int J Hematol. 2013;98:716–718. doi: 10.1007/s12185-013-1454-1.
    1. N'Kontchou G, Seror O, Bourcier V, Mohand D, Ajavon Y, Castera L, Grando-Lemaire V, Ganne-Carrie N, Sellier N, Trinchet JC, et al. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol. 2005;17:179–184. doi: 10.1097/00042737-200502000-00008.
    1. Kim H, Suh KS, Jeon YM, Park MS, Choi Y, Mori S, Hong G, Lee HW, Yi NJ, Lee KW. Partial splenic artery embolization for thrombocytopenia and uncontrolled massive ascites after liver transplantation. Transplant Proc. 2012;44:755–756. doi: 10.1016/j.transproceed.2012.01.066.
    1. Lv Y, Gong X, Xie X, Wang B, Yang Y, Li Y. Clinical study on the relationship between hematocytopenia and splenomegaly caused by cirrhotic portal hypertension. Cell Biochem Biophys. 2014;70:355–360. doi: 10.1007/s12013-014-9920-9.
    1. Yoshida D, Nagao Y, Tomikawa M, Kawanaka H, Akahoshi T, Kinjo N, Uehara H, Hashimoto N, Hashizume M, Maehara Y. Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic patients. Hepatol Int. 2012;6:657–661. doi: 10.1007/s12072-011-9315-6.
    1. Ushitora Y, Tashiro H, Takahashi S, Amano H, Oshita A, Kobayashi T, Chayama K, Ohdan H. Splenectomy in chronic hepatic disorders: portal vein thrombosis and improvement of liver function. Dig Surg. 2011;28:9–14. doi: 10.1159/000321886.
    1. Zhan XL, Ji Y, Wang YD. Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. World J Gastroenterol. 2014;20:5794–5800. doi: 10.3748/wjg.v20.i19.5794.
    1. Tomikawa M, Akahoshi T, Sugimachi K, Ikeda Y, Yoshida K, Tanabe Y, Kawanaka H, Takenaka K, Hashizume M, Maehara Y. Laparoscopic splenectomy may be a superior supportive intervention for cirrhotic patients with hypersplenism. J Gastroenterol Hepatol. 2010;25:397–402. doi: 10.1111/j.1440-1746.2009.06031.x.
    1. Inagaki Y, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, Ogura S, Yamamoto N, Takei Y, Ito M, et al. The long-term effects of splenectomy and subsequent interferon therapy in patients with HCV-related liver cirrhosis. Mol Med Rep. 2014;9:487–492.
    1. Ishigami M, Ishizu Y, Onishi Y, Kamei H, Kiuchi T, Itoh A, Hirooka Y, Katano Y, Goto H. Long-term dynamics of hematological data and spleen volume in cirrhotic patients after liver transplantation-various dynamics depending on etiology. Springerplus. 2013;2:374. doi: 10.1186/2193-1801-2-374.
    1. Chu HC, Hsieh CB, Hsu KF, Fan HL, Hsieh TY, Chen TW. Simultaneous splenectomy during liver transplantation augments anti-viral therapy in patients infected with hepatitis C virus. Am J Surg. 2015;209:180–186. doi: 10.1016/j.amjsurg.2014.03.004.

Source: PubMed

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