Overwhelming Post-Splenectomy Infection: Narrative Review of the Literature

Abstract

Background:

Almost 100 years have passed since the first evidence appeared of the immunologic function of the spleen against infections. The spleen now is recognized as the host for immune cells essential for antibody production and elimination of blood-borne pathogens, particularly encapsulated bacteria. Since the early 1900s, splenectomy has been a frequently performed surgical procedure with multiple indications. Unfortunately, removal of the spleen is associated with increased susceptibility to infection, which may be life-long, and death.

Methods:

Review of the pertinent English-language literature.

Results:

Splenectomized patients are predisposed to overwhelming fulminant infections caused by encapsulated bacteria that are refractory to the usual treatment, with a case-fatality rate of 40% to 54%. Recent studies demonstrate high morbidity.

Conclusions:

Because of this high mortality rate and the challenging treatment, prevention of infection by vaccination is a key feature of the management of splenectomized adult patients.

In 1919, Morris and Bullock opined that removal of the spleen may increase susceptibility to infection and cautioned against indiscriminate removal of this organ [1]. Many years later, King and Shumacker reported a series of cases of severe sepsis in children less than one year of age who had undergone splenectomy. They suggested that when splenectomy was performed, increased vulnerability to infection followed [2]. It is now clear that splenectomized patients are at risk for infectious complications. When fulminant sepsis occurs, the term found commonly in the literature is “overwhelming post-splenectomy infection” (OPSI) [3,4]. These episodes of sepsis have a case-fatality rate of 40% to 54% in some reports and may be associated with substantial morbidity [5,6]. The literature was reviewed in terms of the immune function of the spleen, the risk for sepsis after splenectomy, the microbiology of OPSI, and some therapy- and prevention-related aspects of this pathology.

Immunologic Importance of the Spleen in the Control of Encapsulated Bacteria

The spleen is a unique organ that accommodates the capture and destruction of blood-borne pathogens and the induction of adaptive immune responses. Both innate and adaptive immune functions are combined in a single organ because of its compartmentalization into different specialized regions: The red pulp, the white pulp, and the marginal zone (reviewed recently by Mebius and Kraal [7]). As a blood filter, the spleen removes senescent and damaged erythrocytes from the circulation and phagocytizes microorganisms. Opsonized bacteria are cleared promptly by macrophages in the spleen and liver, but poorly opsonized (encapsulated) bacteria (e.g., Streptococcus pneumoniae) are cleared only by the spleen [8].

The importance of the spleen in controlling invasive pneumococcal infection has been demonstrated in animal models, all of which have confirmed the capability of S. pneumoniae to cause severe infection in splenectomized mice [9 –11]. This specific vulnerability after splenectomy may be related to depletion of marginal-zone macrophages, which are able to phagocytize encapsulated bacteria, and marginal-zone immunoglobulin M memory B cells, which need the spleen for survival/generation and to produce natural antibodies required for protection against pneumococci [12,13]. Immunoglobulin M memory B cells are characterized by few somatic mutations compared with switched-class memory B cells, which have highly mutated V_H sequences and are considered to be the “true memory pool” [13,14]. They also produce antibodies necessary for T-cell-independent immune responses to infection or vaccination with capsular polysaccharide antigens [15]. Conversely, IgM concentrations decrease after splenectomy [16 –18]. Finally, the spleen synthesizes two opsonin proteins: Tuftsin and properdin. Serum concentrations of tuftsin are sub-normal after splenectomy, and this may be correlated with suboptimal phagocytosis and greater susceptibility to infection [19 –21]. In conclusion, removal of the spleen affects the immune system in such a way as to predispose to infection by encapsulated bacteria.

Asplenism and Hyposplenism: Causes

Asplenism means absence of the spleen. It is rarely congenital; the most common cause is surgical intervention. A recent Danish study identified 3,812 splenectomized persons, and the most common indication for surgery was trauma (20.1%) followed by abdominal cancer (19.3%) [22]. A Scottish study evaluated 1,648 patients, and again, most cases of splenectomy in living patients were related to cancer (38.5%) and trauma (24.6%) [23]. Interestingly, the association between splenectomy and an increased long-term risk of infection and death seems to be related to the co-morbidities and indication for surgery, as described below.

A growing number of diseases, including congenital, hematologic, immunologic, infectious, gastrointestinal, and iatrogenic, are associated with hyposplenism (Table 1) [3,16]. In Brazil, sickle cell anemia is the most common monogenic hereditary disease, affecting one of every 1,000 newborn infants [24]. Autosplenectomy as the result of multiple infarctions in patients with sickle cell anemia is the most prominent cause of severe hyposplenism worldwide [4]. Williams et al. stated that children with sickle cell anemia have an odds ratio of 26.3 for developing bacteremia; children older than two years have an odds ratio of 82 compared with control subjects [25]. Some of the reasons for this higher risk might be loss of the spleen secondary to recurrent episodes of infarction during childhood. Pearson et al. proposed that functional asplenism in sickle cell anemia might be related to some degree of reticuloendothelial derangement caused by constant removal of sickled erythrocytes by splenic macrophages [26]. Finally, Spier et al. [27] stated that patients with sickle cell anemia have serum tuftsin concentrations reduced to almost the same degree as those in splenectomized patients, which may predispose to sub-optimal opsonization and facilitate infections [21].

Table 1.

Causes of Hyposplenism

Congenital disorders
• Stormorken syndrome
• Ivemark syndrome
• Congenital asplenia (isolated)
• Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) syndrome
Hematologic diseases
• Hemoglobin S diseases
• Acute leukemia
• Graft-versus-host disease
• Lymphoma
• Systemic mastocytosis
Gastrointestinal diseases
• Celiac disease
• Whipple disease
• Intestinal lymphangiectasia
• Dermatitis herpetiformis
• Inflammatory bowel disease
Hepatic disorders
• Alcoholism
• Chronic hepatitis
• Hepatic cirrhosis
• Portal hypertension
• Primary biliary cirrhosis

Autoimmune disorders
• Systemic lupus erythematosus
• Sjogren syndrome
• Wegener granulomatosis
• Thyroiditis
• Sarcoidosis
• Glomerulonephritis
• Rheumatoid arthritis
Infectious diseases
• Malaria
• Human immunodeficiency virus/acquired immune deficiency syndrome
Iatrogenic forms
• Methyldopa
• High-dose steroids
• Total parenteral nutrition
• Splenic irradiation
• Thorotrast exposure
Miscellaneous
• Amyloidosis
• Hypopituitarism
• Old age
• Primary pulmonary hypertension

Adapted from Di Sabatino et al. [3] with permission from Elsevier, and from William et al. [16] with permission from Maney Publishing.

Evaluation of Splenic Function

The ^99mTc sulfur-colloid liver–spleen scan is the gold standard for evaluation of splenic function because the uptake rate correlates well with splenic function [28,29]. Unfortunately, its use in clinical practice is limited by its high cost, qualitative results, and radiation exposure. At the bedside, methods based on evaluation of the presence of erythrocyte membrane abnormalities, denoting less “reticuloendothelial surveillance,” are more suitable [3,29]. These methods include detection of Howell-Jolly bodies (red blood cells with nuclear remnants) and counting “pitted erythrocytes.”

Howell-Jolly bodies can be identified easily in peripheral blood smears. They represent the basophilic DNA remains from the nucleus of erythrocyte precursor cells [30]. Because these nuclear remnants usually are removed by the spleen, their presence suggests poor splenic function [26]. However, the correlation between Howell-Jolly bodies and scintigraphy is poor [31], suggesting that the sensitivity of this test is inadequate in patients with mild splenic hypofunction [32]. Improved Howell-Jolly body quantification has been provided by flow cytometry. This method allows evaluation of a larger number of erythrocytes and has a good correlation with splenic dysfunction in infants with sickle cell anemia. A Howell-Jolly body count of ≥665/10⁶ erythrocytes predicts absent splenic function [28].

Hyposplenism also induces characteristic erythrocyte membrane “pits,” which are visible by interference phase microscopy. The presence and number of these pits correlate well with splenic hypofunction [28,33]. Nevertheless, pitted erythrocyte counts require specific equipment (Nomarski optics). A pitted cell count of ≥4.5% correlates with poor splenic function [28]. At present, some authors suggest using the number of pitted cells as a rapid and accessible method for bedside investigation, and refer patients with abnormal values to scintigraphy [30].

Sepsis after Splenectomy: Risk Factors and Mortality Rate

The overall risk of OPSI has been estimated to be from 2.9% to 7% [5,6,23,34,35]. Many of the discrepancies among studies that have evaluated the incidence of OPSI are related to differences in case definitions of severe infection, type of study, population enrolled, follow-up period, and quality of the information obtained from the database analyzed (Table 2). Some of the older studies included case series [5,34]. Recently, some epidemiologic studies from Denmark, Scotland, and Australia demonstrated the population impact of post-splenectomy infections [22,23,35,36]. Of note, these studies considered as “serious infections” some well-known diseases; e.g., meningitis or bacteremia, but also episodes of infection that required hospitalization. This latter definition is vague, as it may include uncomplicated as well as life-threatening conditions.

Table 2.

Studies that Evaluated the Incidence of Severe Infections after Splenectomy

Series	Incidence (%)	Definition	Study type	Population	Follow-up
Holdsworth et al., 1991 [34]	3.6	“Septicemia,” meningitis, and severe pneumonia	Review of case series from the literature (1952–1987)	Children and adults	>20 y
Bisharat et al., 2001 [5]	3.2	“Septicemia” and meningitis	Review of case series from the literature (1966–1996)	Children and adults	Median of 6.9 y
Ejstrud et al., 2000 [35]	7.0	Bacteremia	Epidemiologic retrospective study (1984–1993)	Danish county (North Jutland) population	Up to 11 yrs (1,731 person-years at risk)
Kyaw et al., 2006 [23]	3.0	“Septicemia” and meningitis	Epidemiologic retrospective study (1988–1997)	Scottish population	Mean of 4.45 y
Thomsen et al., 2009 [22]	25.1	Infection episode requiring hospitalization	Epidemiologic retrospective study (1996–2005)	Danish population	Median of 2.2 y
Dendle et al., 2012 [36]	26.0	Infection episode requiring hospitalization	Epidemiologic retrospective study (1998 to 2006)	Victoria (Australian city) population	Mean of 3 y

Note the wide ranges of incidences of severe infections, probably as a result of different definitions.

The risk for serious infections post-splenectomy is highest from three to 12 months after surgery. In the study of Ejstrud et al., 45% of cases of bacteremia occurred within 30 d after surgery [35], and more than one-half of all severe infections in the study of Kyaw et al. occurred in the first year after splenectomy [23]. Thomsen et al. documented that splenectomized patients have an increased risk for bacteremia within 90 d of surgery (large relative risk of 138 compared with the general population). Even after adjustment for underlying illness, the risk was 3.2-fold higher [22]. Much of this augmented susceptibility soon after splenectomy might be related to the loss of IgM memory B cells, which decrease exponentially within the first 100–150 d but stabilize beyond that time [37], and the immediate removal by splenic clearance of poorly opsonized bacteria and particulate matter [8,38,39]. The risk later decreases but remains elevated [22,35].

There are some notable risk factors for the occurrence of severe infections after splenectomy (Table 3). Age is associated with increased susceptibility to infection in both elderly persons and children [23,34]. In patients older than 50 years of age, Kyaw et al. showed a rate of severe infection from 9–14 per 100 person-years, which is higher than that in the overall population [23]. Holdsworth et al. demonstrated that more than one-half of cases in children occurred before the age of 15 years [34]. This might be related to their limited immunologic experience as a result of youth [8] and the lack of vaccination at the time of the study. Pneumococcal vaccination is now a standard of care in many countries. The incidence of infection in vaccinated splenectomized pediatric patients is unknown.

Table 3.

Risk Factors for Severe Infections after Splenectomy ^a

• Age

Children and elderly are more susceptible

• Co-morbidities

Thalassemia

Sickle cell anemia

Hematologic malignant disease

Trauma (compared to nonsplenectomized trauma patients)

• Previous episodes of infections after splenectomy

See text for more details.

Co-morbidities are another relevant risk factor for infectious complications after splenectomy. The epidemiologic studies mentioned previously [5,34] found that the most important diseases associated with a higher risk of infection are thalassemia (incidence of 7%–8.2%), sickle cell anemia (7.3%), and Hodgkin lymphoma (4.1%–7.1%). Although trauma patients have an incidence of 1.5%–2.3% [5,34], one prospective multi-center study involving 269 trauma patients identified splenectomy as an independent risk factor for infectious complications (adjusted odds ratio 9.62; 95% confidence interval 3.04–30.30; p<0.001). Even among those with the most severe splenic lesions (grades III–V), splenectomy remained the most significant independent risk factor for infection (adjusted odds ratio 16.67; 95% confidence interval 3.76–71.43; p<0.001) [40]. Thus, splenectomized trauma patients have a higher risk of serious infection than do non-splenectomized trauma patients.

As in some other types of infection, episodes of severe infection after splenectomy increase the risk for another. In the retrospective evaluation of Kyaw et al., the overall rate for the first episode was 7 per 100 person-years. This rate increased to 44.9 for the second episode and 109.3 for the third episode [23].

Mortality rates after each infectious episode are extremely high (40%–54%) [2,5,6,23,34,35]. A similar risk is observed for mortality. Splenectomized children have a higher mortality rate after infection [5,34], as do patients older than 70 years (the mean survival time after splenectomy in elderly patients is 2.86 years) [23]. The indication for splenectomy also is related to the mortality rate: Thalassemia, sickle cell anemia, and hematologic malignant tumors are associated with higher death rates [5,6,23,34]. Finally, the early period (<90 d after surgery) is associated with an elevated relative risk of death compared with the general population (relative risk 33.6; 95% confidence interval 6.9–35.0). When compared with a matched-indication cohort, patients with hematopoietic cancer had a higher short- (<90 d) and long- (>90 d) term mortality risk [41].

Microbiology of OPSI

For reasons described above, S. pneumoniae is the most common pathogen reported in case series of OPSI. Reports from the 1990s and early 2000s show that the pneumococcus was responsible for the majority of infections (57%–87%) [5,6,34]. More recently, Williams et al. detected S. pneumoniae in 41% of Kenyan children with sickle cell anemia, making it the most common bacterial isolate from this population [25]. Nevertheless, other reports contradict this role of the pneumococcus. Both reports are from Denmark and suggest that gram-negative bacilli, especially Escherichia coli, are the most prevalent bacteria isolated during bacteremia in splenectomized patients [22,35]. This may be a regional phenomenon because the same group documented that E. coli is the bacterium isolated most frequently during community-acquired bacteremia in their country [42]. The reasons for this finding are unknown; they might be related to recommendations for pneumococcal vaccination after splenectomy and to treatment with penicillin during the same period [35]. Other causative organisms implicated less frequently are Pseudomonas aeruginosa, Neisseria meningiditis, Capnocytophaga canimorsus, Bartonella spp., and Babesia spp. [3,43]. In the context of the study by Williams et al. in Africa, delayed clearance of malaria parasites from red blood cells is observed in splenectomized patients [44].

Clinical Features and Treatment of OPSI

Overwhelming post-splenectomy infection is an aggressive disease and a medical emergency because of its fulminant evolution. Early reports described rapid cardiovascular collapse and death within 12 h [45 –47], with most of the deaths occurring within 24 h of the onset of symptoms [34]. The prodrome, if present, is vague and short, with malaise, fever, shivering, myalgia, headache, vomiting, and abdominal pain progressing rapidly to coma, refractory septic shock, hypoglycemia, anuria, and disseminated intravascular coagulation (DIC) [45], the latter being an unusual finding in pneumococcal infection in patients with normal splenic function [48]. This frequent complication of OPSI might be related to the high burden of pneumococcus in the circulation (the pneumococci may be seen in blood smears) [46], which presents large amounts of pneumococcal capsular polysaccharide antigens to body fluids [49]. Activation of the complement pathway by polysaccharide-specific antibodies promotes deposition of complement fragments directly onto the pneumococcal capsule. This is associated with thrombotic complications and vessel occlusion [50], which might be an explanation for the association of OPSI and disseminated intravascular coagulation (DIC). One last important clinical feature is the frequent pathologic finding of bilateral adrenal hemorrhage, mimicking Waterhouse-Friderichsen syndrome [45]. Thus, administration of corticosteroids may be indicated.

The most important aspect in the approach to asplenic patients with fever is to suspect OPSI until proved otherwise. Patients with severe sepsis or septic shock should be evaluated according to international guidelines [51], even in the absence of clear signs of hypoperfusion. As in patients with severe sepsis, the diagnostic investigation should never postpone administration of broad-spectrum antibiotics. Standard laboratory tests should include serum lactate concentration, hematologic profile, serum electrolytes, renal function tests, and blood glucose concentration. Radiologic studies should be performed as indicated, although in most cases, no obvious focus of infection will be identified [29]. A peripheral blood smear and buffy-coat preparation should be examined for the presence of bacteria using Gram or Wright staining while awaiting the results of blood cultures [46,52]. Samples for other cultures (e.g., urine) should be collected as appropriate.

Prompt administration of empiric broad-spectrum antibiotics is essential [53,54]. There is compelling evidence that effective antimicrobial therapy within the first hour of severe sepsis is associated with a better survival rate [55]. Initial antibiotics are focused on coverage of the most likely pathogens, especially pneumococcus. Previous reviews have suggested regimens such as third-generation cephalosporins (cefotaxime 2 g q 8 h or ceftriaxone 2 g q 12 h) with vancomycin (1–1.5 g q 12 h) in cases of suspected resistance to benzylpenicillin or possible infections caused by Staphylococcus (chemotherapy-induced mucositis, catheter-related sepsis). However, the latest guideline from the British Committee for Standards in Haematology suggests that the choice of antibiotics should be made with consideration of local protocols and typical microorganisms and susceptibilities. Attention should be given to pediatric patients receiving antibiotic prophylaxis because there must not be cross-resistance between the antibiotic class chosen for treatment and that used in prophylaxis [56].

Prevention of OPSI

Because OPSI is associated with high mortality rates even with adequate treatment, its prevention is a key feature in the management of patients with an absent or dysfunctional spleen. In 1996, the British Committee for Standards in Haematology published the first guidelines regarding prevention and treatment of infections in asplenic or hyposplenic patients [57]. These guidelines were reviewed and updated in 2002 [58] and again in 2011 [56]. Their recommendations can be divided broadly into three categories: Patient education, vaccination, and antibiotic prophylaxis [52,56,59,60]. Unfortunately, the recommendations are not followed. For example, some recent studies demonstrated that 15% to 25% of splenectomized patients did not receive pneumococcal vaccination, and the majority (70%–75%) did not receive meningococcal group C vaccination [61,62]. Clearly, many improvements in prophylaxis are needed.

Education

The majority (as many as 84%) of splenectomized patients are unaware of their increased susceptibility to infection and the health precautions needed in case of procedures or febrile illness [63]. Unfortunately, much of this unawareness might be attributable to incomplete information and lack of adequate education provided to patients and their relatives. Brigden et al. demonstrated that only 6% of discharge summaries after splenectomy procedures mentioned the need for future re-vaccination, and just a few (5%) raised the possibility of future infection risk [64]. Other studies confirmed that the majority of patients had not been advised adequately [6], and that in most of the cases, the recommendations were not transmitted to their primary care practitioners [61]. Thus, efforts are needed to ensure adequate education and adherence to vaccination because this may reduce the incidence of OPSI [65].

Patients and their families should be educated regarding the risk of bacterial infection, tactics to prevent infection, and the importance of prompt recognition and treatment of infection. This information should be given in both written and electronic form [56]. Patients also should be encouraged to wear an alert bracelet or equivalent or carry an alert card with information about their conditions and other clinical details. This is intended to increase the awareness of patients and their physicians, serve as a constant reminder of their condition, and improve the speed and appropriateness of treatment for OPSI [52,56,59]. Patients should seek medical advice before travel, especially to areas where malaria or babesiosis is endemic. Early medical attention also is recommended in cases of animal bites. Registration in a “spleen registry system,” where available, may be helpful [66].

Vaccination

All asplenic or hyposplenic patients should receive pneumococcal, Haemophilus influenzae type b, meningococcal, and annual influenza vaccinations [56]. These vaccines have clinical effectiveness and thus are a major recommendation for infection prophylaxis. Even in splenectomized patients, immunization seems to be partially responsible for a reduction in sepsis incidence [64,67].

Because S. pneumoniae is a prominent etiologic agent in OPSI, immunization against pneumococcus is indicated in asplenic or hyposplenic patients [56]. There are two types of pneumococcal vaccines: Capsular polysaccharide and protein–polysaccharide conjugate (PCV). The PPV-23 vaccine contains purified capsular polysaccharide from 23 serotypes (1–5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F) that account collectively for most cases (85%–90%) of invasive pneumococcal disease among adults in the United States [68]. The antibody response to PPV-23 is primarily T-cell-independent and offers protection by enhancing phagocytosis [29]. It also may reduce the occurrence of OPSI [67]. When indicated, it should be given at least 2 wks before splenectomy or initiation of immunosuppressive treatments [56]. If this is not possible (e.g., unexpected or emergency splenectomy), vaccination should be given 14 d after surgery because functional antibody activity is significantly better after that time [68]. Close attention is necessary to ensure that patients are not lost to follow-up before the first vaccination. If there is any doubt about patient compliance, one dose of pneumococcal vaccine might be offered before discharge.

Re-vaccination at 5-yr intervals is indicated [56]. However, protective antibody concentrations decline more rapidly in some subgroups (e.g., patients with sickle cell anemia or lymphoproliferative diseases) [3]. Thus, measurement of antibody titers might be appropriate to assess when re-vaccination is needed. The World Health Organization has recommended a serotype-specific IgG concentration of ≥0.35 mcg/mL as a protective threshold, although this cutoff is considered a benchmark for conjugate vaccine comparison and not a formal clinical mean to be achieved [70,71]. Nevertheless, most splenectomized patients become immune after PPV-23 vaccination [72].

Regrettably, some patients mount an impaired immune response to PPV-23, especially splenectomized patients with hematologic malignancies [73,74]. These non-responders are at high risk for invasive pneumococcal infections, and other prophylactic measures must be offered [74,75]. Re-vaccination with PPV-23 usually is not effective [74].

The pneumococcal PCV is made by coupling selected capsular polysaccharides to protein molecule carriers such as diphtheria toxoid or tetanus toxoid. In contrast to PPV-23, the conjugated vaccines induce T-cell-dependent immunity, are more immunogenic (even in infants under 2 yrs of age), and elicit immune memory [70]. The PCV-7 vaccine includes serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The novel PCV-13 vaccine includes serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, and 23F and is expected to replace the other pneumococcal conjugate vaccines. In asplenic adult patients who are good serologic responders to PPV-23, PCV does not seem to have additional benefits [72]. However, in patients who respond poorly to PPV-23, PCV immunization may be beneficial [75,76]. In this situation, two doses four weeks apart are suggested to achieve a good serologic response [76].

Vaccination for H. influenzae type b and N. meningiditis is recommended for asplenic or hyposplenic patients [56]. One dose of H. influenzae type b conjugate vaccine is indicated for adults irrespective of their immunization status. The timing of the first dose is the same as that for pneumococcal vaccination. For meningococcal vaccination, it is suggested to give one dose of group C conjugate vaccine followed by a single dose of the quadrivalent ACWY conjugate vaccine 1 mo later, irrespective of immunization status [56]. This is especially important for those who will travel to countries with an increased prevalence of serogroup A, W135, or Y. There is no recommendation to re-vaccinate for H. influenzae type b or meningococcus [77]. These recommendations are in concordance with the most recent Surgical Infection Society Guidelines for vaccination after splenectomy [77].

Antibiotic prophylaxis

Although antibiotic prophylaxis is recommended for some high-risk patients according to the latest guidelines [56], there are only two controlled trials from the 1980s evaluating the efficacy of prophylactic penicillin in children with sickle cell anemia [78,79]. In one of these trials, the patients also received pneumococcal vaccine, which makes evaluation of the sole contribution of antibiotics difficult [78]. Life-long penicillin prophylaxis also has many drawbacks, including reduced efficacy because of poor adherence, side effects from the antibiotics (e.g., allergy, Clostridium difficile infection [80]), and selection of resistant bacterial strains. Nevertheless, in high-risk patients, the British guidelines suggest counseling on its use and follow-up for adherence [56].

As described above, the high-risk population comprises the following individuals [56]: Children younger than 16 yrs and adults older than 50 yrs of age [23,34]; those with a previous episode of invasive pneumococcal infection [23]; those who have undergone splenectomy because of hematologic malignant diseases, other malignant neoplasms, and thalassemia [5,34]; and those in the first year after splenectomy, irrespective of cause [22,23,35]. Patients with sickle cell anemia [5,34] and who respond poorly to PPV-23 also are at continued high risk [74,75]. Other, low-risk patients might not benefit from any protection from antibiotic prophylaxis and may stop using it.

Oral penicillins still are the prophylactic drugs of choice [76], but they are becoming less effective with the development of resistant pneumococcal strains in many countries. Some authors have suggested antibiotics with a broader spectrum of activity, such as amoxicillin–clavulanic acid, trimethoprim–sulfamethoxazole, or cefuroxime [52]; however, resistance to these agents has been detected. All hyposplenic patients should carry a supply of appropriate antibiotic to be administered should symptoms or signs of systemic infection develop (e.g., high fever), but this measure should not delay presentation to the hospital.

Conclusions

Almost 100 years have passed since the first description by Morris and Bullock of the relation between splenectomy and higher life-long susceptibility to infection. Since that time, much progress has been made in splenic physiology and immunology, the microbiologic and clinical features of OPSI, and the importance of immediate treatment. Although these episodes are aggressive and have a high fatality rate, they remain largely preventable. Continuous patient education, vaccination, and prompt and careful assessment of febrile episodes are indicated and may reduce the incidence of OPSI and its mortality rate.

Footnotes

Author Disclosure Statement

The authors declare that they have no competing interests.

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