Patients who are asplenic, either because of physical absence of a spleen or functional splenic compromise, are at an increased risk of contracting a lifethreatening condition known as overwhelming postsplenectomy infection (OPSI). This infection is commonly described as a fulminant bacteremia that develops very quickly and carries a high mortality rate. The incidence of OPSI has been difficult to establish, partially because of the wide variation in occurrence rates among particular groups of patients. In one population-based study, the incidence of OPSI in splenectomy patients was found to be 0.23%.1 However, other studies have demonstrated rates of serious bacterial infection as high as 21% to 22% in patients with specific medical conditions, such as thalassemia major or hematologic malignancy.2,3 The risk of contracting OPSI can vary depending on how long the patient has been asplenic. For most patients, the risk of sepsis is substantially increased in the first 2 to 3 years following splenectomy. However, patients have developed life-threatening infection as many as 10 years after their surgery.4 The lifetime risk of OPSI has been estimated at 5%.5
While the risk of contracting OPSI may be low in some populations, once an infection occurs, the mortality rates are high, ranging from 38% to 69%, and fulminant infections frequently develop in patients who are relatively young and have few other health problems.6 Early diagnosis and intervention are the keys to a good outcome. The purpose of this article is to encourage PAs to identify patients who are at risk of developing sepsis and establish care plans designed to prevent or limit overwhelming infection, thereby reducing the morbidity and mortality associated with OPSI.
SPLENIC FUNCTION AND ASPLENIA
The spleen's primary function is to filter the blood. Through a process known as culling, abnormal or senescent erythrocytes are removed from the bloodstream and phagocytosed during their slowed circulation through the spleen. The spleen is also responsible for eliminating intra-erythrocyte inclusions, such as Heinz bodies, Howell-Jolly bodies (see Figure 1), and Pappenheimer bodies, through a similar process termed pitting.
Bacteria are cleared from the bloodstream in a process that is expedited by opsonization—the coating of microorganisms with complement fragments. These coated bacteria join with circulating antibodies to form immune complexes, which are then trapped and destroyed by both the liver and the spleen. Encapsulated bacteria are more difficult for the body to eradicate because of their resistance to complement binding. Clearance of these bacteria is facilitated by opsonins, such as antigen-specific IgM, an immunoglobulin manufactured and secreted by the B cells present in lymph tissue, such as lymph nodes and the spleen. Patients lacking a functioning spleen have fewer of these opsonins, resulting in a limited ability to filter circulating encapsulated bacteria.7 The bacteria multiply rapidly, culminating in the development of overwhelming sepsis and shock.
CAUSES OF ASPLENIA
Asplenia is most commonly caused by surgical removal of the spleen. Splenectomy is undertaken on an elective basis for a variety of hematologic conditions, such as hereditary spherocytosis, autoimmune thrombocytopenia, primary hypersplenism, and -thalassemia; or for neoplastic diseases, such as Hodgkin's lymphoma.8 Splenectomy is performed emergently for severe bleeding caused by blunt or penetrating injuries. Splenic function may also decline over a period of time because of a specific medical condition. Termed functional hyposplenia or functional asplenia, this phenomenon is associated with sickle cell disease, celiac disease, inflammatory bowel disease, alcoholic liver disease, and systemic lupus erythematosus.9 Significantly reduced splenic function can be diagnosed by the presence of Howell-Jolly bodies, fragments of RBC nuclei remaining after hematopoiesis and seen as pits or craters on the surface of erythrocytes on a peripheral blood smear.10 These bodies increase in number as splenic function declines, and their presence is a strong indicator of risk for bacterial infection.
IMPLICATED BACTERIA
Asplenic patients are susceptible to a host of pathogenic microorganisms. Streptococcus pneumoniae is the most common pathogen implicated in OPSI and may be responsible for up to 90% of these overwhelming infections.6 Other encapsulated bacteria, such as Haemophilus influenzae type b and Neisseria meningitidis, are also known to be causative agents. Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are less commonly involved.1 Occasionally, asplenic patients may develop fulminant sepsis from Capnocytophaga canimorsus (a type of bacteria associated with dog bites). In addition, asplenic patients have an increased risk of developing debilitating infections from the parasites Babesia microti and Plasmodium falciparum.11-13 Coexisting medical conditions, such as malignancy or immunosuppressive disorders, may predispose asplenic patients to infection, further increasing their risk for OPSI.
DIAGNOSING AND TREATING INFECTION
The clinical presentation of OPSI often begins with mild, nonspecific symptoms. Patients usually have a fever and may complain of headache, chills, malaise, and various GI symptoms. However, this prodrome is usually very brief and progresses rapidly to symptoms of septic shock, including hypotension, oliguria, hypoglycemia, and disseminated intravascular coagulopathy. Patients may develop concomitant meningitis or pneumonia, or they may experience convulsions or cardiovascular collapse. Death can occur within 24 to 48 hours of illness onset.14 Mortality is high despite aggressive antibiotic therapy and intensive medical care, and patients who survive often have prolonged and complicated recovery periods with serious long-term sequelae, such as deafness; osteomyelitis; or extensive tissue necrosis, which may potentially require amputation when extremities are involved.15
Diagnosis of a bacterial infection and subsequent identification of the involved pathogen are accomplished through laboratory testing. Blood, urine, and sputum should be cultured on hospital admission. Blood cultures often display positive results within 24 hours and are helpful in directing antibiotic therapy. However, initiation of treatment should never be postponed until the results of these tests are available because bacterial proliferation occurs at an accelerated pace. The number of bacteria observed on the peripheral smear of some asplenic patients has suggested bacterial counts greater than 1 million/mL.14 A CBC and serum chemistries are usually ordered as well. Lumbar puncture is an important tool in diagnosing possible meningitis, especially in small children, and chest radiographs are indicated anytime pneumonia is suspected. The decision on what other studies to order should be based on the patient's presenting symptoms.
Empiric oral antibiotics may be started by the patient at home, or antibiotics can be given IM or IV at the primary care provider's office.16 The antibiotic of choice for treating OPSI has traditionally been IV penicillin. However, with the increasing prevalence of resistant bacterial infections, many providers are choosing broader-spectrum antibiotics.17 One source suggests that patients be given an initial dose of ceftriaxone 100 mg/kg IV or IM, maximum 2 g per dose, before being transported to the nearest emergency department.18 IV vancomycin 60 mg/kg/d in divided doses every 6 hours, maximum 4 g per day, should be added to a ceftriaxone regimen after hospital admission in regions with high levels of penicillin-resistant pneumococci.14 Regimens may be adjusted as the results of sensitivity testing become available.
