REVIEW Complications of Splenectomy Ali Cadili, aMD, Chris de Gara, MD, FRCS(c)b aUniversity of Alberta;bRoyal Alexandra Hospital, Alberta, Canada ABSTRACT Surgical removal of the spleen, splenectomy, is a procedure that has significantly decreased in frequency as our understanding of the infectious complications of the asplenic state increased. The full spectrum and details of splenic function, however, have yet to be fully outlined. As a result, our comprehension of the long-term consequences of splenectomy remains incomplete. We review the evidence relating to the effects of splenectomy on infection, malignancy, thrombosis, and transplantation. Perhaps the best-defined and most widely understood complication of splenectomy is the asplenic patient’s susceptibility to infection. In response to this concern, novel techniques have emerged to attempt functionto preserve in those splenic patients for whom surgical therapy of the spleen is necessary. The efficacy of these techniques in preserving splenic function and staving off the complications associated with splenectomy is also reviewed in this article. © 2008 Elsevier Inc. All rights • reserved.The American Journal of Medicine (2008) 121, 371-375 KEYWORDS: Asplenia; Complications; Postsplenectomy; Spleen; Splenectomy; Surgery The spleen is well known to be the largest lymphoidSplenectomy organ is frequently preformed for a multitude of in the body. Unlike the lymph nodes, however, thereasons, spleen including trauma and various pathologic processes. does not receive drainage from the lymphatic systemBlunt but abdominalis trauma remains the most common indica- rather connected to the systemic circulation. The spleen’stion for splenectomy, but patients with a variety of hema- functions are many, but they are generally in 1 tologicof 4 disorderscate- also benefit from this procedure. In addi- gories: filtration, immunologic, reservoir, and hematopoi-tion, splenectomy also is performed in cases of iatrogenic etic functions. In terms of immunologic function, theinjury spleen and involvement by adjacent pathologic processes, is only one of many organs, such as lymph nodesfor anddiagnostic liver, purposes, and for relief of hypersplenism or that provide immune protection to the body. Manysplenomegaly. of the Although some of the infectious complica- spleen’s immunologic functions, therefore, are in commontions are well known, efforts have mounted in clarifying with these other immunologic organs. On the otherother hand, consequences of asplenia. Such consequences may several immunologic roles are uniquely exercised by the include effects on malignancy, transplantation, and throm- spleen. For example, the spleen is more efficient at remov- bosis. Awareness of the infectious sequelae of splenectomy ing non-opsonized bacteria, mostly encapsulated organisms, has increased the emphasis on nonoperative management of than is the 1liver. It is the main site of immunoglobulin-M antibody synthesis. Serum immunoglobulin-M havelevels splenic injuries. In addition, a multitude of techniques to been shown to decrease significantly after splenectomy.2 preserve splenic function, especially in children, have sur- The spleen is also the main site of the opsoninsfaced tuftsin in andcases in which splenic trauma/pathology cannot properdin synthesis.3 Serum tuftsin levels beenhave shown be safely observed. Examples of such techniques include to decrease after splenectomy,4 and tuftsin deficiency maysplenic repair, partial splenectomy, partial splenic angioem- precede overt hyposplenism in conditions leading to functionalbolization, and splenic autotransplantation. The exact effi- asplenia.5 It is this specificity in splenic function, alongcacy ofwith such efforts in staving off the complications asso- the lack of ability of other organs to compensate, ciatedthat withrenders total splenectomy has generated controversy. In the asplenic state ripe with immunologic sequelae. this review, we examine the consequences of splenectomy as they relate to 4 key areas: infection, cancer, thrombosis, and transplantation. We also examine the evidence concern- Requests for reprints should be addressed to Ali Cadili, MD, University of Alberta Hospital, Edmonton T6G 2B7, Alberta, Canada. ing the role of spleen-preserving procedures in mitigating E-mail address: [email protected] those complications. 0002-9343/$ -see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2008.02.014 372 The American Journal of Medicine, Vol 121, No 5, May 2008 INFECTION have demonstrated accelerated tumor growth when splenec- Asplenia has been known to predispose one to infection.6 A tomy is performed late after tumor transplantation and re- particularly significant and specific infectious complication tarded growth when it is performed before or early after 11 of splenectomy is overwhelming postsplenectomy infec- tumor transplantation. One study found that splenectomy tion.7 This is caused by encapsulated organisms such as Strep- performed early after the development of melanoma in mice tococcus pneumoniae, Neisseria reduced tumor growth and in- meningitidis, and Hemophilus in- creased mouse survival, but when fluenzae type B. This condition, performed long before melanoma CLINICAL SIGNIFICANCE 12 which occurs at an annual fre- development it had no effect. quency rate of 0.5% in patients ● The major impact of splenectomy/asple- Another study found that a small postsplenectomy,8 is associated nia relates to issues in 1 of 4 categories: amount of tumor cells relative with a 50% mortality rate.7 The infection, malignancy, thrombosis, and to spleen cells stimulated tumor risk of overwhelming postsple- transplantation. growth, whereas a large amount of nectomy infection increases with tumor cells relative to spleen cells 13 younger age at the time of sple- ● Infectious and thrombotic complications inhibited tumor growth. Other nectomy and reduced time inter- of the postsplenectomy state are well studies performed on rats with val from splenectomy.8 Although documented and deserve special periop- mammary tumors revealed that the risk is highest in the first 2 erative management and discussion with splenectomy inhibits malignant de- years after splenectomy, patients the patient. generation of benign tumors but are thought to harbor a lifelong, does not retard established car- ● 14 albeit undefined, risk of develop- The ideal perioperative management of cinogenesis. Firm conclusions ing the condition. Several methods infectious and thrombotic complications based on these animal studies re- have been shown to be effective of splenectomy needs further clarifica- main elusive given the different in preventing overwhelming post- tion with ongoing and future studies. methodologies, animal subjects, and tumors studied. In addition, splenectomy infection in patients ● Evidence regarding the effects of sple- the extrapolation of these find- postsplenectomy. Such methods nectomy on malignancy and transplan- include patient education, pro- ings to human subjects remains tation remains inconclusive and not well phylactic antibiotics, and vaccina- problematic. tion against encapsulated bacteria. studied. Few clinical studies on humans Multiple reviews, however, have have examined the effect of sple- documented that the implementa- nectomy on carcinogenesis. A tion of such methods has been widely variable and generally study from Denmark followed a suboptimal.9 Also, the optimal duration of antibiotic pro- cohort of 6315 patients who had undergone splenectomy for 15 phylaxis in patients postsplenectomy has yet to be deter- a variety of reasons. With a mean follow-up of 6.8 years, mined. Thus, overwhelming postsplenectomy infection re- no increase in cancer risk was detected among the patients mains a menacing problem in the asplenic patient. who had a splenectomy performed for trauma. Among pa- In addition to encapsulated organisms, the asplenic pa- tients who had a splenectomy performed for nontraumatic tient is at an increased risk for the development of other causes, however, a 2-fold increase in cancer risk was noted. types of infections. Gram-negative organisms, Capnocyto- This striking result should be interpreted with caution be- phaga canimorsus, and intraerythrocytic parasites, such as cause it may be confounded by the carcinogenicity of the Babesia microti and Plasmodia falciparum, have all been underlying condition, prior chemotherapy or radiotherapy, implicated as presenting a higher risk than average in sple- and patient factors such as age and smoking. A Swedish nectomized patients.10 The risk of infectious complications study that followed 2280 patients for an average of 11.8 is the most widely understood among the features defining years revealed no increased risk of cancer among patients 16 the unique postsplenectomy state. splenectomized for trauma. This study did show a non- significant increase in cancer risk for patients who had an incidental splenectomy performed for nonmalignant condi- MALIGNANCY tions. As in the case of postsplenectomy infection, the risk The question of whether asplenia predisposes one to in- of cancer was found to be higher in younger patients. An creased cancer growth or recurrence has been the subject of older study of 740 American veterans who underwent sple- considerable investigation. Numerous experimental studies nectomy after trauma also showed no increased risk of in animals have examined the role of splenectomy on tumor cancer.17 On the other hand, splenectomy performed as part growth and progression.