INTRODUCTION — Fever in a patient with impaired splenic function is a warning sign for possible sepsis and should be treated as a medical emergency. Asplenic and functionally hyposplenic patients are at risk for severe and overwhelming infections with encapsulated bacteria (eg, Streptococcus pneumoniae), bloodborne parasites, and other infections that the spleen plays an important role in controlling. Infection with these pathogens can be rapidly fatal, and immediate empiric antibiotic administration is critical to care.
The clinical features, common causes, and management of sepsis in the asplenic patient will be reviewed here. The prevention of sepsis in the asplenic patient is discussed separately. (See "Prevention of infection in patients with impaired splenic function".)
ROLE OF THE SPLEEN IN INFECTION — The spleen plays a central role in clearing pathogens from the bloodstream and controlling infections, particularly with encapsulated bacteria. Within the red pulp of the spleen, sinusoids serve as mechanical filters that remove rigid particles >1 micron in size from circulation, including senescent and/or parasitized red blood cells, and unopsonized bacteria (figure 1) [1,2]. Macrophages, positioned along the sinusoids, eliminate some infected cells or bacteria via phagocytosis and also produce proinflammatory cytokines in response to infection . The white pulp of the spleen houses approximately half of the body's immunoglobulin-producing B lymphocytes, which are critical for producing antibodies that target polysaccharide antigens on the surface of encapsulated bacteria.
DEFINITIONS — Both anatomic and functional asplenia and hyposplenism predispose to infection (table 1).
●Asplenia refers to complete loss of function of the spleen and may be anatomic or functional. Anatomic asplenia is most often due to surgical splenectomy, performed for trauma or therapeutically (eg, for hemolytic anemias or immune thrombocytopenias) . Functional asplenia refers to complete loss of function caused by medical conditions and occurs most frequently with sickle cell anemia . Rarely, the spleen is congenitally absent.
●Hyposplenism refers to partial loss of splenic function and is most often caused by medical disorders that lead to atrophy, infarction, engorgement, or infiltration of the spleen, such as thalassemias, chronic liver disease, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), immune disorders, or malignancies . (See "Splenomegaly and other splenic disorders in adults", section on 'Asplenia or hyposplenia'.)
RISK OF SEVERE INFECTION — The risks of infection, sepsis, and sepsis-related mortality appear to be approximately two to three times higher in asplenic patients when compared with the general population [6,7]. In a cohort study evaluating over 8000 splenectomized patients over a 27-year period, splenectomized patients had increased rates of sepsis (rate ratio [RR] 3.38, 95% CI 3.12-3.67) and sepsis-related mortality (RR 3.02, 95% CI 1.80-5.06) when compared with matched controls . The increased risk for sepsis and sepsis-related mortality were sustained over a 10-year period and are presumed to be lifelong . Because these studies included patients using antibiotic prophylaxis, the actual risk of infection is likely higher.
Among patients with impaired splenic function, higher rates of infection have been observed in children and older adults [9-11]. Patients with asplenia or hyposplenism related to hemoglobinopathies, hematologic malignancies, immunodeficiencies, and inflammatory diseases (eg, systemic lupus erythematosus) have been reported to have higher rates of severe infections when compared with patients who have undergone splenectomy for trauma [9,11-15]. However, these associations have not been consistently observed across studies [7,11].
Asplenic patients with a history of severe infections appear to be predisposed to having subsequent episodes . In a retrospective review of over 1600 splenectomized patients, the incidence of severe infection was sixfold higher among patients with a history of severe infection compared with patients without such history . Among asplenic patients, lack of vaccination against encapsulated organisms, such as S. pneumoniae, also raises the likelihood of severe infection [13,16].
FEVER AND OVERWHELMING SEPSIS
Identifying patients at risk — We generally consider all patients with anatomic asplenia at risk for severe and overwhelming sepsis (table 1).
Determining the risk of severe infection and overwhelming sepsis among patients with functional splenic loss is less straightforward. Because this risk is not equal among patients with functional hyposplenism, we generally individualize our approach to management.
We favor treating patients with functional asplenia or hyposplenism similarly to patients with anatomic asplenia when they present with severe illnesses (eg, sepsis) or when they have a history of recurrent bacterial infections and/or when testing results suggest loss of splenic function (eg, presence of Howell-Jolly bodies on blood smear (picture 1) or low number of circulating immunoglobulin [Ig]M memory B cells).
The best method for assessing splenic function is not established. When splenic function is in doubt, we typically obtain a peripheral blood smear to assess for Howell-Jolly bodies. Their presence correlates with impaired splenic function (picture 1) and serves as a useful screen for clinically significant dysfunction and risk of sepsis [17,18]. Volumetric assessment of the spleen can be performed with Tc99m sulfur colloid liver-spleen scintigraphy and SPECT imaging , and functional assessment can be achieved using Tc99m labeled heat-treated autologous erythrocytes followed by scintigraphy and multimodality SPECT imaging . Quantitation of erythrocyte pitting, another measure of splenic functional assessment, can be performed using interference contrast microscopy . The latter two assays are not necessarily routinely available and have not been compared in large populations of patients with impaired splenic function to assess test sensitivity and specificity. In some institutions, additional testing options are available, such as quantification of memory B cells by flow cytometry. However, the best method for assessing splenic function has not been determined. (See "Splenomegaly and other splenic disorders in adults", section on 'Asplenia or hyposplenia'.)
Clinical features — Fever in a patient with impaired splenic function should be interpreted as an early sign of sepsis. Without prompt and appropriate treatment, infections in asplenic and hyposplenic patients can become fulminant and fatal within hours of symptom onset [21-24].
The most common foci of infection accompanying sepsis in asplenic and hyposplenic patients are pneumonia, primary bacteremia, and meningitis [10,13]. Signs and symptoms of these infections can be nonspecific in early illness and include chills, malaise, headache, and gastrointestinal complaints (eg, nausea, vomiting, diarrhea, and abdominal pain) .
Fulminant sepsis has been reported to quickly follow even minor complaints and can also develop precipitously without specific antecedent symptoms [22,25]. As illness progresses, high-grade bacteremia, hypotension, endovascular injury, and disseminated intravascular coagulation can ensue, leading to the development of purpura fulminans, extremity gangrene, and even autoamputation [26-28]. Metastatic infection (eg, septic arthritis, meningitis, or pericarditis) may also become evident.
While the dominant characteristic of sepsis in patients with impaired splenic function is its rapid progression, certain clinical and/or epidemiologic features raise suspicion for specific pathogens (table 2). (See 'Important pathogens' below.)
Important pathogens — Fulminant sepsis in patients with impaired splenic function is most often caused by encapsulated bacteria, including S. pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Other bacterial pathogens, including Capnocytophaga canimorsus and more common bacteria such as Klebsiella pneumoniae, can provoke similar syndromes of fulminant sepsis. Infections caused by bloodborne parasites, such as malaria and babesiosis, can also be particularly severe in asplenic patients (table 2).
Streptococcus pneumoniae (pneumococcus) — The single most important pathogen is S. pneumoniae. This organism accounts for approximately 40 to 60 percent of cases of severe infection and overwhelming sepsis in splenectomized patients [10,13,14]. Although the overall incidence of S. pneumoniae infections is declining because of widespread pneumococcal vaccination [29,30], patients with impaired splenic function are still at higher risk for S. pneumoniae infection and poorer outcomes when compared with patients who have normal splenic function [13,16,31]. In a prospective cohort study evaluating over 2400 patients with invasive pneumococcal disease, asplenic patients were more likely to have meningitis (22 versus 5 percent), require intensive care unit admission (51 versus 28 percent), and require mechanical ventilation (41 versus 22 percent) . In-hospital mortality was higher in asplenic patients when compared with patients with spleens (18.9 versus 15.6 percent); however, this difference was not statistically significant.
The clinical syndromes associated with S. pneumoniae infection in patients with impaired splenic functions are similar to those seen in other patients and include pneumonia, bacteremia, and meningitis. Initial symptoms can be nonspecific (eg, fever, rigors, malaise, nausea, vomiting, and diarrhea) but progress to severe sepsis within hours . In keeping with the increased severity of illness observed in asplenic patients, purpura fulminans appears to be more common in asplenic patients with pneumococcal infections when compared with patients who have normal splenic function . Clinical features of S. pneumoniae infections are discussed in detail separately. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults" and "Pneumococcal pneumonia in patients requiring hospitalization".)
Haemophilus influenzae type b — H. influenzae type b was previously among the more common causes of sepsis in patients with impaired splenic function, but its incidence has declined sharply with widespread use of the conjugate H. influenzae type b vaccine [10,11,13]. Clinical syndromes associated with severe H. influenzae type b infections include pneumonia, bacteremia, and meningitis. (See "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Clinical manifestations'.)
Neisseria meningitidis (meningococcus) — N. meningitidis is a less common cause of severe and overwhelming infections in patients with impaired splenic function, accounting for <3 percent of reported cases . Whether it is more prevalent in patients with impaired splenic function than in the general population is not clear . The primary clinical syndromes associated with N. meningitidis infection are meningitis and meningococcemia. Even among patients with normal splenic function, early symptoms of meningococcal disease can be nonspecific and "flu-like" followed by rapid progression to septic shock, which is frequently accompanied by disseminated intravascular coagulation and purpura fulminans. (See "Clinical manifestations of meningococcal infection".)
Other encapsulated bacteria — Other encapsulated bacteria that have been reported to cause severe and overwhelming sepsis in asplenic patients include Capnocytophaga species, Bordetella holmesii (which is putatively encapsulated), and K. pneumoniae [33-36].
●Capnocytophaga spp – C. canimorsus and, less commonly, C. cynodegmi are transmitted to humans primarily via dog bites [36-39]. Approximately 12 percent of reported cases of infection with these organisms occur in asplenic patients . The primary clinical syndromes associated with Capnocytophaga infections include sepsis, meningitis, cellulitis, purpura fulminans, and gangrene. The associated mortality among asplenic patients is approximately 30 percent . (See "Capnocytophaga" and "Capnocytophaga", section on 'Clinical manifestations'.)
●Bordetella holmesii – B. holmesii is a respiratory pathogen that primarily causes pertussis-like symptoms in immunocompetent persons; however, knowledge of this organism is limited [34,40-42]. Among immunocompromised patients, extrapulmonary and invasive infections have been reported largely in patients with impaired splenic function and include cellulitis, septic arthritis, sepsis, pericarditis, and endocarditis [35,42-44]. While these infections can be severe among asplenic patients, fatal cases have not been reported . The incidence of severe B. holmesii infections appears to correlate with pertussis outbreaks.
Infections with K. pneumoniae do not appear to be more common in patients with impaired splenic function when compared with patients with normal splenic function but can be rapidly progressive and fatal [13,33,45].
Bloodborne parasites — Babesia and Plasmodium parasites invade red blood cells, and clearance of infection with these organisms is reduced in patients with impaired splenic function.
●Babesia spp – Babesiosis is a tickborne illness characterized by fever, malaise, myalgias, arthralgias, and hemolytic anemia. Patients with impaired splenic function are at risk for high-grade parasitemia and severe infection, which can progress to acute respiratory distress syndrome, multiorgan failure, and disseminated intravascular coagulation [46,47]. Persistent and relapsing babesiosis appears to be more common among patients with impaired splenic function . Fatal cases are uncommon but have been reported [49,50]. (See "Babesiosis: Clinical manifestations and diagnosis".)
Most cases occur in coastal New England during the warmer months when tick activity is high. However, babesiosis occurs sporadically in other regions of the United States as well as in Europe, Asia, and Australia. Babesiosis can also be transfusion transmitted and has been confused with hemolytic transfusion reactions leading to delayed diagnosis among asplenic patients with hemoglobinopathies [51-53]. (See "Babesiosis: Microbiology, epidemiology, and pathogenesis", section on 'Epidemiology'.)
●Plasmodium spp – Plasmodium parasites are the causative agents of malaria. The presence of fever should raise suspicion for malaria in patients who have recently traveled to or live in areas where malaria is endemic (ie, most tropical regions of the world, especially sub-Saharan Africa). Additional clinical features vary based on the infecting Plasmodium species and immune status of the patient. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)
The degree to which asplenia or hyposplenism alters the course of malaria is unclear. Patients with impaired splenic function who have not been previously exposed to malaria may have prolonged fever, persistent parasitemia, and delayed responses to therapy due to the loss of splenic filtration [54,55]. Severe and fatal infections have also been reported [54,56]. In contrast, immune individuals who are reinfected following splenectomy appear to have a typical mild course of infection, suggesting that the spleen is not required for the immune sequestration of infected erythrocytes .
Other pathogens — Staphylococcus aureus, Escherichia coli, and other pathogens that commonly cause bacteremia have been reported to cause overwhelming infections in patients with impaired splenic function [10,11,13]. Cytomegalovirus [58,59], Mycoplasma pneumoniae , Mycobacterium tuberculosis , and Ehrlichia species  have also been reported to cause unusually severe or fatal infections among asplenic patients. However, whether splenic impairment is truly a risk factor for infection with these pathogens is not established.
EVALUATION AND MANAGEMENT
Initial triage and management — Immediate empiric antibiotic administration and aggressive supportive care are crucial for the management of sepsis in patients with impaired splenic function [5,63,64].
●We advise all asplenic and hyposplenic patients who develop fever to take an oral antibiotic (if on hand) AND present to the nearest emergency department immediately (table 3 and table 4). (See "Prevention of infection in patients with impaired splenic function", section on 'Emergency antibiotic supply'.)
●Upon arrival to the emergency department, we recommend starting empiric intravenous broad-spectrum antibiotics immediately (table 5). Administration of antibiotics should not be delayed in order to perform diagnostic studies, including lumbar puncture. (See 'Empiric antibiotic selection' below.)
Because progression to septic shock and respiratory distress can occur rapidly, preparations for fluid resuscitation, vasopressor support, and airway management should be made. (See "Evaluation and management of suspected sepsis and septic shock in adults" and "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)".)
Generally, we admit asplenic and hyposplenic patients with fever and/or sepsis to the hospital for at least 72 hours for close monitoring, supportive care, and empiric antibiotic treatment while the diagnostic evaluation is pending.
Initial diagnostic evaluation — As with other patients with sepsis, the initial evaluation should be directed at assessing the severity of infection and identifying its source. In addition to a thorough history (including past immunizations) and physical examination, we generally include or consider the following tests or procedures in our evaluation (table 6):
●Routine laboratory tests – Laboratory testing is similar to other patients with sepsis (eg, complete blood count with differential, comprehensive metabolic panel, coagulation studies, and lactate). We also send an arterial or venous blood gas for patients with signs of hemodynamic instability.
Like other septic patients, the white blood cell count may be elevated or markedly depressed. An elevated creatinine and hepatic transaminases may signify the onset of multiorgan dysfunction. In asplenic patients, progression to disseminated intravascular coagulation (DIC) often occurs early in the course of illness.
●Peripheral blood smear – The peripheral smear usually demonstrates a marked left shift with bands and early myeloid forms. Blood smears also demonstrate Howell-Jolly bodies (picture 1), reflecting the loss of splenic function. Intracellular or extracellular bacteria can occasionally be visualized directly on the peripheral blood smear or via Gram or Wright stain on the white cell buffy coat, reflecting high-grade bacteremia (picture 2) .
●Quantitative immune globulins – In addition to the laboratory tests outlined above, some UpToDate authors and editors send a quantitative immunoglobulin G level because adjunctive therapy with intravenous immune globulin (IVIG) may be warranted in patients with low levels and other selected patients. (See 'Intravenous immune globulin' below.)
●Blood cultures – Blood cultures should be obtained before the start of antibiotics, when feasible. Cultures can be obtained when intravenous (IV) access is established to avoid further delay in the administration of parenteral antibiotic therapy. Because of the high bacterial loads in asplenic and hyposplenic patients, cultures may turn positive within hours of inoculation.
●Coronavirus disease 2019 (COVID-19) testing – During the pandemic, we test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in all patients with fever. (See "COVID-19: Diagnosis".)
●Other microbiologic testing – Because of the high rates of pneumococcal infection in asplenic and hyposplenic patients, we obtain urine S. pneumoniae antigen testing in adults in addition to blood cultures. Additional microbiologic testing (eg, sputum, urine, throat, and/or cerebrospinal fluid [CSF] culture) should be obtained based on the suspected site of infection and individual patient risk or epidemiologic risk factors (eg, testing for seasonal influenza). Cutaneous lesions can also be aspirated for Gram stain and culture. Blood pneumococcal and/or meningococcal polymerase chain reaction may be available at some institutions.
●Imaging – Chest radiographs are warranted in nearly all patients due to increased likelihood of pneumonia. Other imaging tests should be obtained based on the suspected sites of infection (eg, sinus or abdominal computed tomography scan).
●Lumbar puncture – Our threshold for obtaining a lumbar puncture is low in patients with impaired splenic function because of their increased risk for bacterial meningitis. We usually perform a lumbar puncture in patients with nonlocalizing neurologic dysfunction who have normal platelets and coagulation studies. However, it is common for lumbar puncture to be deferred because of the development of DIC. For patients who do undergo lumbar puncture, a normal or only slightly abnormal CSF profile does not necessarily rule out bacterial meningitis. Patients may become ill so quickly that characteristic changes (eg, marked neutrophilic pleocytosis) may not be observed early in the course of meningitis.
Empiric antibiotic selection
Standard regimen — For most asplenic and hyposplenic adults and children who present with fever and/or other signs of sepsis, we select an empiric antibiotic regimen that includes coverage for S. pneumoniae, H. influenzae type b, and N. meningitidis (table 5). Because of the increased prevalence of meningitis among these patients, we dose these antibiotics for CSF penetration.
●For asplenic and hyposplenic adults in whom meningitis is strongly suspected based on clinical features (eg, fever, headache, altered mental status, and neck stiffness), we typically give adjunctive dexamethasone at the time of antibiotic administration. For children with suspected bacterial meningitis, we decide when to use adjunctive dexamethasone on a case-by-case basis. (See 'Dexamethasone for meningitis' below.)
●For selected asplenic and hyposplenic patients with severe sepsis, disseminated intravascular coagulation, or for those with additional immunocompromising conditions, we often give intravenous immune globulin in addition to antibiotics. (See 'Intravenous immune globulin' below.)
Modifications to this regimen may be needed for patients with risk factors for other infections that may be particularly severe in patients with impaired splenic function, such as animal bites or travel to regions where malaria is endemic. (See 'Unusual exposures' below.)
As with any septic patient, additional adjustments to the empiric antibiotic regimen may be needed based on the suspected source of infection, relevant exposures, risk of infection with antibiotic-resistant pathogens, patient comorbidities, and other factors. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Empiric antibiotic therapy (first hour)' and "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)", section on 'Empiric antibiotic therapy'.)
Our antibiotic recommendations are based on knowledge of the pathogens that are most likely to cause sepsis in patients with impaired splenic function and their antimicrobial resistance patterns. Ceftriaxone and cefotaxime are both active against most S. pneumoniae, H. influenzae type b, and N. meningitidis isolates. Vancomycin is added to the regimen to treat potential beta-lactam-resistant S. pneumoniae. Controlled trials evaluating treatment regimens in this patient population have not been performed.
Penicillin and cephalosporin allergy — The main alternatives to cephalosporins include an extended-spectrum fluoroquinolone (eg, moxifloxacin or levofloxacin) and meropenem (table 5). Selection among these agents depends on the type of drug reaction (table 7), patient age, and severity of illness.
●For most asplenic and hyposplenic adults who have a history of an IgE-mediated reaction or a serious delayed reaction to penicillins and/or cephalosporins, we treat empirically with vancomycin plus moxifloxacin.
●For most asplenic and hyposplenic children who have a history of an IgE-mediated reaction or a serious delayed reaction to penicillins and/or cephalosporins (table 7), we treat empirically with vancomycin plus levofloxacin. While moxifloxacin has greater activity against many of the pathogens that commonly cause meningitis in asplenic patients and has been tolerated among children treated for drug-resistant tuberculosis, experience in treating bacterial meningitis in children with moxifloxacin is limited. A dose of 5 mg/kg IV every 24 hours was used in a case report in a neonate with meningitis , and a subsequent study suggests that moxifloxacin may be well tolerated in children .
Following the first dose of antibiotics, we generally consult an allergist to determine whether the patient can be transitioned to a cephalosporin or carbapenem following a test dose procedure or if skin testing and/or desensitization is needed and/or recommended. (See "Choice of antibiotics in penicillin-allergic hospitalized patients" and "Cephalosporin hypersensitivity: Clinical manifestations and diagnosis".)
An alternate approach for adults and children who have a history of IgE-mediated reactions to penicillin or cephalosporins or mild delayed reactions to cephalosporins is to treat with meropenem. This approach is preferred by some experts, particularly for patients with meningitis and/or severe sepsis because the likelihood of cross-reactivity is low and meropenem has greater activity against the pathogens that commonly cause severe infections in patients with impaired splenic function.
Adults and children with a history of a mild, non-IgE-mediated reaction to penicillins can generally tolerate cephalosporins, and we treat these patients with the standard regimen outlined above. (See 'Standard regimen' above.)
Unusual exposures — Impaired splenic function is an important risk factor for overwhelming infection with Capnocytophaga species, which is typically transmitted by dog bites, but scratches and animals other than dogs can also be a source. Infections with bloodborne parasites, such as babesiosis and malaria, can also be particularly severe in patients with impaired splenic function. While infections with these pathogens are overall uncommon in asplenic patients, early diagnosis and appropriate treatment can improve outcomes.
●Animal bites - For asplenic and hyposplenic patients with an antecedent dog bite (or other animal bite), we treat with vancomycin plus a beta-lactam-beta-lactamase inhibitor combination antibiotic, such as piperacillin-tazobactam (4.5 g every six hours), or meropenem (2 g every eight hours) to target Capnocytophaga species. If meningitis is suspected, we select meropenem over piperacillin-tazobactam because of its higher CSF penetrance. (See 'Other encapsulated bacteria' above and "Capnocytophaga", section on 'Treatment'.)
●Bloodborne parasites - For asplenic and hyposplenic patients with concern for babesiosis based on risk factors (eg, tick bite or transfusion in an endemic area) and compatible clinical features (eg, fever, myalgias, arthralgias, hemolytic anemia), we include treatment for this parasite in our initial antibiotic regimen. The diagnostic evaluation and treatment recommendations are the same as for patients with normal splenic function. However, severe and relapsing infections are more likely in patients with impaired splenic function, and, in some cases, exchange transfusion and longer treatment courses may be warranted. (See "Babesiosis: Treatment and prevention" and 'Bloodborne parasites' above.)
The treatment of malaria in patients with impaired splenic function is the same as for patients with normal splenic function. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children" and "Treatment of severe malaria".)
Dexamethasone for meningitis — Dexamethasone may reduce neurologic complications and mortality in selected patients with bacterial meningitis. The benefits appear to be greatest in adults with S. pneumoniae meningitis, followed by children with H. influenzae meningitis.
●For asplenic and hyposplenic adults with known or suspected bacterial meningitis, we generally give adjunctive dexamethasone (0.15 mg/kg every six hours) when it can be administered immediately prior to the first dose of antibiotics because of the high rates of S. pneumoniae infection in these patients. Delaying the administration beyond one hour following the first dose of antibiotics does not appear to provide benefit. For patients with microbiologically confirmed S. pneumoniae meningitis, we continue dexamethasone for a total of six days. For all others, we discontinue dexamethasone when S. pneumoniae meningitis has been excluded or is determined to be unlikely. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
●For asplenic and hyposplenic children with suspected bacterial meningitis, we generally individualize the decision to give dexamethasone because rates of H. influenzae meningitis are low and the benefits of adjunctive dexamethasone in children are less certain. For children with impaired splenic function with suspected bacterial meningitis, administering dexamethasone is also logistically difficult. Because antibiotics are often given immediately at the onset of fever and because dexamethasone should be given before or at the same time as antibiotics in order to be beneficial, it is infrequently used. (See "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications".)
Intravenous immune globulin — Use of IVIG in patients with sepsis is controversial and not routinely recommended for the general population. However, patients with splenic dysfunction have specific deficits in antibody production, opsonization and phagocytosis of intravascular pathogens, and impaired antibody responses to vaccination. Because IVIG has the potential to offset these immune deficits [67-69], it is reasonable to give IVIG to selected patients with sepsis who have impaired splenic function.
Although practice varies, some UpToDate authors and editors favor the use of IVIG (1 g/kg on day 1, followed by 0.5 g/kg on days 2 and 3) in the following patients with known or suspected impaired splenic function:
●Sepsis complicated by hemodynamic instability that is nonresponsive to fluid resuscitation and/or DIC
●Sepsis with an additional immunocompromising condition (eg, patients with primary immunodeficiencies)
●Sepsis in patients who have not been vaccinated against S. pneumoniae or H. influenzae
●Sepsis in patients who have low immune globulin levels (eg, IgG <400 mg/dL)
Our IVIG dosing recommendations are derived from the treatment of streptococcal toxic shock syndrome. (See "Overview of intravenous immune globulin (IVIG) therapy" and "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'Intravenous immune globulin'.)
Response to treatment — We generally monitor patients in a hospitalized setting, continue broad-spectrum antibiotics, and provide supportive care (as needed) for at least 72 hours while awaiting results of our diagnostic evaluation.
●For patients in whom the source of infection is identified, we tailor our antibiotic regimen and treatment plan to target the source.
●For patients who are well-appearing in whom no bacterial source is identified or suspected, we typically discontinue antibiotics after 72 hours of empiric therapy and provide close follow-up. Some experts continue empiric antibiotics (eg, intramuscular ceftriaxone or an oral fluoroquinolone) for a total of 7 to 10 days, particularly for patients who received antibiotics prior to blood cultures whose initial laboratory findings are consistent with early sepsis and/or for patients with known or suspected viral respiratory tract infections because of the risk for bacterial superinfection.
●For patients who fail to improve with empiric therapy, we broaden our differential diagnosis to include the possibility of infection with an antibiotic-resistant organism (eg, highly penicillin-resistant or fluoroquinolone-resistant S. pneumoniae), infections with less common pathogens (eg, Bordetella holmesii or babesiosis), and complications of infection (eg, empyema or abscess) and adjust our treatment approach as needed. Unfortunately, some patients will progress to shock, multiorgan failure, and DIC despite appropriate treatment.
COVID-19 considerations — The evaluation and management of COVID-19 in patients with impaired splenic function is generally similar to patients with normal splenic function, however, the thresholds for treating COVID-19 infections in this population with monoclonal antibodies such as sotrovimab or direct-acting antiviral agents such as nirmatrelvir-ritonavir and providing pre- and postexposure prophylaxis are lower. (See "COVID-19: Management in hospitalized adults", section on 'COVID-19-specific therapy' and "COVID-19: Epidemiology, virology, and prevention", section on 'Monoclonal antibodies ineffective for pre-exposure prophylaxis' and "COVID-19: Epidemiology, virology, and prevention", section on 'Post-exposure management'.)
While patients with impaired splenic function do not appear to be at increased risk for SARS-CoV-2 infection, the risk of developing severe disease may be higher. In one case-control study, evaluating >165,000 patients with COVID-19 and 493,300 matched controls, the risk acquiring COVID-19 was similar; the risk of hospitalization and death was higher, though did not reach statistical significance (adjusted odds ratio for combined endpoint 1.44, 95% CI 0.79-2.61) . There are no data to clarify whether specific SARS-CoV-2 variants have selective virulence against individuals with impaired splenic function.
PROGNOSIS — Reported mortality rates range widely from approximately 10 to 70 percent in patients with impaired splenic function and likely vary with the infecting pathogen, patient comorbidities, duration of illness prior to presentation, and compliance with the immediate administration of oral antibiotic therapy at the onset of symptoms, other factors [13,22]. With early recognition of sepsis, aggressive supportive care, and immediate administration of appropriate antibiotics, mortality can be substantially reduced and approach that observed in the general population .
PREVENTION — Key preventive measures include patient education on the risk of sepsis and strategies to decrease that risk; vaccination against S. pneumoniae, H. influenzae type b, N. meningitidis, influenza, and SARS-CoV-2; and prophylactic antibiotics. (See "Prevention of infection in patients with impaired splenic function".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Infections in asplenic patients".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Splenectomy (The Basics)")
●Beyond the Basics topic (see "Patient education: Preventing infection in people with impaired spleen function (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Risk of overwhelming infection − Patients with impaired splenic function are at risk for severe and overwhelming infection with encapsulated bacteria, bloodborne parasites, and other infections that the spleen plays a critical role in controlling. (See 'Introduction' above and 'Role of the spleen in infection' above.)
●Important pathogens − Streptococcus pneumoniae is the most common cause of fulminant sepsis in patients with impaired splenic function, followed by Haemophilus influenzae and Neisseria meningitidis. Less common causes of severe infections and sepsis include other encapsulated bacteria such as Capnocytophaga spp, Bordetella holmesii, and bloodborne parasites, such as Babesia spp and Plasmodium spp (table 2). (See 'Important pathogens' above.)
●Fever as an early sign of sepsis − Fever in a patient with impaired splenic function should be interpreted as an early sign of sepsis. Without prompt and appropriate treatment, infections in asplenic and hyposplenic patients can become fulminant and fatal within hours of symptom onset. (See 'Clinical features' above and 'Identifying patients at risk' above.)
●Initial management of fever
•Because of this risk, we advise asplenic and hyposplenic patients who develop fever to take an oral antibiotic (if on hand) AND present to the nearest emergency department immediately (table 3 and table 4). (See 'Initial triage and management' above and "Prevention of infection in patients with impaired splenic function" and "Prevention of infection in patients with impaired splenic function", section on 'Emergency antibiotic supply'.)
•Upon arrival to the emergency department, we start empiric intravenous broad-spectrum antibiotics immediately (table 5). For most asplenic and hyposplenic patients, we give vancomycin plus either ceftriaxone or cefotaxime. Administration of antibiotics should not be delayed in order to perform diagnostic studies, including lumbar puncture. (See 'Initial triage and management' above and 'Empiric antibiotic selection' above.)
•Modifications to these regimens may be needed based on suspected source of infection, exposure history, risk for multidrug-resistant pathogens, renal dysfunction, and other patient-specific factors including antibiotic allergy. (See 'Empiric antibiotic selection' above and 'Penicillin and cephalosporin allergy' above and 'Unusual exposures' above.)
•As with other patients with sepsis, the initial evaluation should be directed at assessing the severity of infection and identifying its source (table 6). (See 'Initial diagnostic evaluation' above.)
●Close monitoring − We generally admit asplenic and hyposplenic patients with fever and/or sepsis to hospital for at least 72 hours for close monitoring, supportive care, and empiric antibiotic treatment while the diagnostic evaluation is pending. (See 'Response to treatment' above.)
●Preventive measures − Key measures for preventing infection in patients with impaired splenic function include patient education; vaccination against S. pneumoniae, H. influenzae type b, N. meningitidis, SARS-CoV-2, and influenza; and antibiotic prophylaxis. (See "Prevention of infection in patients with impaired splenic function".)
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