A wide variety of diseases are associated with splenomegaly, or enlargement of the spleen, with many of the mechanisms leading to this condition being exaggerated forms of normal spleen function. (See Etiology.)
The spleen is a functionally diverse organ with active roles in immunosurveillance and hematopoiesis. It lies within the left upper quadrant of the peritoneal cavity and abuts ribs 9-12, the stomach, the left kidney, the splenic flexure of the colon, and the tail of the pancreas. A normal spleen weighs 150 g and is approximately 11 cm in craniocaudal length.
The normal spleen is usually not palpable, although it can sometimes be palpated in adolescents and individuals with a slender build. However, an enlarged or palpable spleen is not necessarily of clinical significance. Moreover, certain individuals with broadly splayed costal margins have readily palpable, but small, spleens. (See Presentation.)
Spleens weighing 400-500 g indicate splenomegaly, and some authors consider spleens weighing more than 1000 g to indicate massive splenomegaly. Spleens that are prominent below the costal margin typically weigh 750-1000 g. Poulin et al defined splenomegaly as moderate if the largest dimension is 11-20 cm, and severe if the largest dimension is greater than 20 cm. (See Treatment and Workup.)
In many instances, the spleen enlarges as it performs its normal functions. The 4 most important normal functions of the spleen are as follows:
As previously mentioned, many of the mechanisms leading to an enlarged spleen are exaggerated forms of normal spleen function. Although a wide variety of diseases are associated with enlargement of the spleen, the following 6 etiologies of splenomegaly are considered primary:
Miscellaneous causes of splenomegaly include trauma, cysts, hemangiomas, metastasis, giant abscess (see the images below), and certain drugs (eg, RhoGAM).
This patient has a splenic abscess due to pneumococcal bacteremia. Note that the massively enlarged spleen is readily visible, with minimal retraction....
Resected specimen from the patient in the previous image. Note the discrete abscesses adjacent to normal parenchyma.
This is an acute enlargement of the spleen that develops in association with various infections or inflammatory processes and results from an increase in the defense activities of the organ. The demand for increased antigen clearance from the blood may lead to increased numbers of reticuloendothelial cells in the spleen and stimulate accelerated antibody production, with resultant lymphoid hyperplasia. Examples include splenomegaly from lupus and Felty syndrome, and from viral infections such as Ebstein Barr Virus–induced mononucleosis.
In this setting, splenomegaly is thought to reflect work hypertrophy that results from the removal of abnormal blood cells from the circulation (either cells with intrinsic defects or cells coated with antibody) or, in some cases, that results from extramedullary hematopoiesis (ie, myeloproliferative disease).
This condition develops as a result of cirrhosis with portal hypertension, splenic vein occlusion (thrombosis), or congestive heart failure (CHF) with increased venous pressure.
In this setting, splenomegaly is the result of engorgement of macrophages with indigestible materials (eg, sarcoidosis, Gaucher disease, amyloidosis, metastatic malignancy).
Splenic filtering of blood-borne pathogens, especially encapsulated organisms, may lead to abscess formation. Because many splenic abscesses may be indolent in presentation, splenic size may be increased as the abscess enlarges. This is a relatively uncommon, but important, process to recognize and treat.
In the United States, one large series reported a palpable spleen in 2% of patients, and another, in 5.6% of patients. Tropical splenomegaly syndrome has the highest predilection for indigenous persons of and visitors to the malarial belt of tropical Africa.
No race predilection is recognized for splenomegaly. However, note that blacks may have hemoglobin SC disease, a disorder related to sickle cell disease. Unlike sickle cell disease that results in a small, autoinfarcted spleen, patients with hemoglobin SC disease may have splenomegaly that accompanies their pigment gallstones.
Tropical splenomegaly syndrome (or hyperactive malarial syndrome) has a female-to-male incidence ratio of 2:1. Otherwise, no sex predilection is documented for splenomegaly.
No age predilection is recognized for splenomegaly. Nonetheless, the capsules of older spleens are much thinner than their younger counterparts. The combination of capsular thinning with increased spleen weight and size makes splenic injury more common in elderly persons. These factors account for the increased likelihood of splenectomy for trauma in this subgroup.
The prognosis for patients with splenomegaly is usually excellent and not substantially different from age-matched controls, but it is impacted by the underlying disease state rather than the presence of splenomegaly or the postsplenectomy state.
Morbidity and mortality in cases of splenomegaly principally stem from associated disease states or surgical procedures, rather than from the splenomegaly itself. The rates for morbidity and mortality are highly variable and relate to the presence or absence of comorbidities, hemorrhage, and organ failure.
Patients with enlarged spleens are more likely to have splenic rupture from blunt abdominal or low thoracic trauma. These patients are unlikely to undergo nonoperative management of their splenic injury or splenic salvage maneuvers, because their spleen is abnormal with regard to architecture, capsule tensile strength, and, commonly, hemostatic function.
Patients with splenomegaly need education with regard to decreasing their risk of splenic hemorrhage. These patients must be cautioned about contact sports and other activities that may acutely increase intra-abdominal pressure or place excessive forces on the left upper quadrant, left flank, or lateral back. This decreases the likelihood of splenic rupture in a patient with an abnormal splenic mass and capsule. The routine use of seat belts is essential while driving or riding in a motor vehicle.
Additional education regarding the signs and symptoms of postsplenectomy sepsis cannot be overstressed. Prompt antibiotic therapy may be lifesaving.
Education represents a mandatory strategy in the prevention of overwhelming postsplenectomy infection (OPSI). Asplenic patients should be encouraged to wear a Medi-Alert (Pinellas Park, Fla/Henderson, Nev) bracelet and carry a wallet card explaining their lack of a spleen. Patients should also be aware of the need to notify their physician in the event of an acute febrile illness, especially if it is associated with rigors or systemic symptoms.
For patient education information, see the Infections Center, as well as Mononucleosis (Mono).
The most common history in patients with splenomegaly is mild, but vague, abdominal pain. Pain may be referred to the left shoulder. Increased abdominal girth is less common. Early satiety from gastric displacement occurs with massive splenomegaly. Associated symptoms or signs are typically related to the underlying disorder and may include the following:
Splenic size is not a reliable guide to splenic function, and palpable spleens are not always abnormal. Patients with chronic obstructive pulmonary disease (COPD) and low diaphragms commonly have palpable spleens. In one study, 3% of college freshmen had palpable spleens; an additional study showed that 5% of hospitalized patients with normal spleens based on scan results were thought to have palpable spleens by their physicians.
The physical examination should include palpation with the patient in the supine and right lateral decubitus position, with knees up and hips flexed. Apply light fingertip pressure as the patient slowly inspires. The use of the reverse Trendelenburg position may aid in bringing the spleen into contact with the examiner's fingers. This is especially helpful in patients with morbid obesity. The spleen moves with respiratory patterns and may be palpable only at the end of inspiration.
In extreme splenomegaly, shown in the image below, the lower splenic pole may extend into the pelvis or cross the abdominal midline. In these circumstances, palpation at the pelvic brim or the right upper quadrant may be necessary to delineate splenic size and location.
The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18 kg (7 lb) spleen crosses the midline. Inferiorly, it extend....
Percussion of the abdomen may disclose caudal displacement of the gastric bubble in massive splenomegaly. Additional signs that identify possible etiologies of splenomegaly include the following:
Perform a complete blood count (CBC) with differential, platelet count, and peripheral blood smear in cases of splenomegaly.
In imaging studies, a craniocaudal measurement of 11-13 cm is frequently used as the upper limit of normal splenic size. However, because of wide variations in shape, no consistent correlation has been recognized between the spleen's length and its overall volume, as has been determined for other organs (eg, kidney).
Angiographic findings are used to differentiate splenic cysts from other splenic tumors. Splenoportography is used to evaluate portal vein patency and the distribution of collateral vessels before shunt operations for cirrhosis. Splenoportographic findings can help to identify the cause of idiopathic splenomegaly, especially in children.
Ultrasonography is a noninvasive, highly sensitive, and specific imaging technique for the evaluation of splenic size.
The term hypersplenism describes some of the sequelae that are often observed with splenomegaly. Criteria for a diagnosis of hypersplenism include anemia, leukopenia, thrombocytopenia, or combinations thereof, plus cellular bone marrow, splenomegaly, and improvement after splenectomy.
The anemia observed in splenomegaly results from sequestration and hemodilution.
Increased destruction or sequestration of leukocytes causes the leukopenia observed in splenomegaly. Leukopenia is closely related to neutropenia. Neutropenia (absolute neutrophil count [ANC] < 2000 × 106/L) is the result of an increase in the marginated granulocyte pool, a portion of which is located in the spleen. Sequestration may also play a role in the genesis of neutropenia.
Approximately 30% of the total platelet mass exists as an exchangeable pool in the spleen. Increased splenic platelet pooling is the primary cause of the thrombocytopenia of hypersplenism. In patients with hypersplenism, as much as 90% of the total platelet mass can be found in the spleen. In hypersplenism, the platelet count is usually 50,000-150,000/µL.
The underlying histologic anatomy of the spleen largely determines its characteristic appearance on abdominal computed tomography (CT) scans. On unenhanced CT scans, the spleen has an attenuation similar to that of the liver, approximately 40 henry (H). Normally, the liver and spleen densities are within 25H on dynamic contrast-enhanced CT scans.
In general, the spleen can be considered enlarged if its craniocaudal length is more than 10cm on conventional CT scans. A spleen that extends below the lower third pole of the kidney is also indicative of splenomegaly.
A CT scan remains the most useful preoperative investigation to measure splenic volume; to exclude lymph nodes at the splenic hilum; and to detect accessory spleens, splenic abscesses, and perisplenitis.
Findings that indicate radiologic distinction between benign and malignant lesions are inconsistent and cannot be relied on to establish or refute a diagnosis of malignancy.
CT scanning is the imaging study of choice for identification of inflammatory changes. In addition, CT scanning is sensitive for detecting mass lesions, calcifications, infarcts, and cysts.
Erythrocytes are labeled with chromium-51 (51 Cr) , mercury-197 (197 Hg), rubidium-81 (81 Rb), or technetium-99m (99m Tc), and the cells are altered by treatment with heat, antibody, chemicals, or metal ions so that the spleen sequesters them after infusion. A splenic length of greater than 14cm is consider enlarged on liver-spleen scan
A spleen scan is a good noninvasive technique for evaluating splenic size; a close correlation exists between splenic length on the scan images and splenic weight after splenectomy.
A spleen scan is also useful for detecting space-occupying lesions in the splenic substance, evaluating loss of splenic functions, assessing for the absence of a spleen, or determining the presence of an accessory spleen.
History and physical examination, laboratory studies, and CT scanning can help clinicians to determine the etiology of splenomegaly in greater than 90% of cases. Occasionally, however, it is necessary to obtain splenic tissue for pathologic evaluation.
Splenectomy may be considered in certain individuals to determine the etiology of splenomegaly.[7, 8, 9, 10, 11] However, the need for a diagnosis must be carefully weighed against the confounding morbidity associated with the asplenic state. Splenectomy is typically performed laparoscopically; even supramassive spleens can be removed by laparoscopic surgery with minimal morbidity.[11, 12] Splenectomy is therapeutic in individuals with severe pancytopenia due to splenomegaly.
Splenic biopsy may be performed in specialized institutions. Severe bleeding is a frequent complication that limits the usefulness of this procedure.
When referring to an enlarged spleen as hypertrophied, the underlying cause may be hypertrophy or hyperplasia of individual cells. In specific diseases, the splenic architecture is remodeled. For example, in Niemann-Pick disease, sphingomyelin and cholesterol accumulate within large foamy cells, which is characteristic of this disease.
With amyloidosis involving the spleen and resulting in splenomegaly, large hyaline masses are seen as lesions occupying the white pulp space. Two forms exist, including the "sago spleen," in which amyloid deposits are limited to follicles, and the "lardaceous spleen," in which amyloid is deposited in the walls of the splenic sinusoids. In a rare complication of typhoid fever, reactive splenic vasculitis may develop.
Successful medical treatment of the primary disorder in cases of splenomegaly can lead to regression of the hypersplenism without the need for surgery.
Splenectomy is indicated to help control or stage the basic disease in cases of splenomegaly. These diseases can include hereditary spherocytosis, autoimmune thrombocytopenia (ITP) or autoimmune hemolysis, or Hodgkin disease (as part of a staging celiotomy).
Splenectomy is also indicated for the treatment of chronic, severe hypersplenism. This can occur in conditions such as the following:
In rare cases, splenectomy may be used to treat thrombotic thrombocytopenic purpura (TTP); however, therapeutic plasma exchange transfusion (plasmapheresis) has largely supplanted the need for splenectomy.
Inpatient care for patients with splenomegaly depends on the modality used to treat the underlying cause of the condition and on the complications of that care. These therapies are not unique to splenomegaly treatment and, therefore, are not discussed here.
Outpatient care of patients with splenomegaly consists of 3 main focus areas: (1) primary etiologic disease; (2) blood count monitoring, especially when associated with a myeloproliferative disease as the cause; and (3) monitoring for overwhelming postsplenectomy infection (OPSI).
Thrombocytosis may require treatment when the platelet count exceeds 1 million/μL. Multiple modalities have been used to reduce the platelet count or inhibit their thrombotic effects, including hydroxyurea, aspirin, or plateletpheresis (collection and removal of platelets from the circulation). No randomized, placebo-controlled studies have demonstrated a better survival benefit with one therapy over the other. Whether any discrete benefit is gained by also controlling the platelet count remains unclear.
Transfer of patients with splenomegaly is not generally required except for complications of surgery or OPSI. Patients undergoing elective splenectomy for splenomegaly may develop significant hemorrhaging during their operation if difficulty occurs controlling the splenic hilum. Such patients may require abdominal packing and transfer to a tertiary center with personnel who have expertise in angioembolization and splenic resection for splenomegaly.
Such centers usually have the additional resources (eg, a well-stocked blood bank, a tertiary level intensive care unit) to support the organ systems in these patients. Multisystem organ failure is not uncommon following severe hemorrhage, and these patients are no exception.
Consultation with a hematologist is ideal before surgery for enlarged spleens in order to secure necessary blood products. Postoperative management does not usually require intervention from a hematologist.
Chemotherapy is used for hematologic malignancies. Antibiotics are used for infection, with the exception of infection associated with a splenic abscess; this requires surgical intervention.
Immunosuppression is used for autoimmune or inflammatory disorders, treatment of cirrhosis, and CHF. All patients scheduled for elective splenectomy (either diagnostic or therapeutic) should receive a pneumococcal vaccine. Also consider administering prophylaxis against Haemophilus influenzae and Neisseria meningitidis.
The vast majority of splenectomies are performed using laparoscopic techniques. Laparoscopic splenectomy is safe and is associated with reduced hospital stays. Furthermore, this procedure has a postoperative survival advantage when compared with open procedures. Laparoscopic surgery can be performed even on individuals with massive splenomegaly. (See the images below.)[15, 16]
Intraoperative photograph of a laparoscopic splenectomy being taken down using the hanging-pedicle technique. The tip of the spleen is visualized in t....
Massive splenomegaly does not preclude splenectomy through a minimally invasive approach. This photograph depicts a fragmented 3.2 kg (7.05 lb) spleen....
A portion of a massive spleen is extracted via hand-assisted laparoscopy.
Occasionally, a reactive thrombocytosis occurs following splenectomy. Thrombocytosis in the face of splenectomy rarely requires treatment. It is most common in patients with massive splenomegaly from myeloproliferative disorders.
An onset of fever several days following splenectomy can be due to a recrudescence of malaria. This should be considered as a cause of fever in patients who have lived in areas commonly associated with malaria and in persons who abuse intravenous (IV) drugs who share needles.
With Plasmodium malariae infection, this may occur decades after the initial infection. Malaria from P vivax (3-7 y) and P falciparum (about 1 y) remain active for shorter intervals after the initial infection.
Fulminant, life-threatening infection represents a major long-term sequela after splenectomy in patients with splenomegaly. Splenic macrophages play a major role in filtering and phagocytizing bacteria and parasitized blood cells from the circulation. In addition, the spleen is a significant source of antibody production.
Overwhelming postsplenectomy infection (OPSI), also known as postsplenectomy sepsis syndrome, begins as a nonspecific, flulike prodrome that is followed by a rapid evolution to full-blown bacteremic septic shock—accompanied by hypotension, anuria, and clinical evidence of disseminated intravascular coagulation—thus making this syndrome a true medical emergency. The subsequent clinical course often mirrors that of the Waterhouse-Friderichsen syndrome, with bilateral adrenal hemorrhages noted at autopsy.
Despite appropriate antibiotics and intensive therapeutic intervention, the overall mortality rate in older published studies of established cases of OPSI varied from 50-70%. Information now suggests, however, that if patients seek medical attention promptly, the mortality rate may be reduced to approximately 10%. Of those patients who die, more than 50% do so within the first 48 hours of hospital admission.
Most instances of serious infection are due to encapsulated bacteria, such as pneumococci (eg, Streptococcus pneumoniae). Because these organisms are encapsulated and the spleen is integral in the removal of opsonized bacteria, affected patients are at increased risk for unimpeded sepsis. Pneumococcal infections account for 50-90% of cases reported in the literature and may be associated with a mortality rate of up to 60%. H influenza type B, meningococci, and group A streptococci account for an additional 25% of infections.
Possible OPSI involving an asplenic individual constitutes a medical emergency. The critical point in management remains early recognition of the patient at risk, followed by subsequent aggressive intervention. The diagnostic workup should never delay the use of empiric therapy. Possible choices of empiric antimicrobial agents include cefotaxime (adult dose of 2 g IV q8h; pediatric dose of 25-50 mg/kg IV q6h) or ceftriaxone (adult dose of 2 g q12-24h; pediatric dose of 50 mg/kg IV q12h). Unfortunately, some penicillin-resistant pneumococcal isolates are also resistant to cephalosporins. If such resistance is suggested, consider using vancomycin.
The precise incidence of OPSI remains controversial. Overall, the most reliable data related to incidence estimate approximately 1 case occurring per 500 person-years of observation. Asplenic children younger than 5 years, especially infants splenectomized for trauma, may have an infection rate of greater than 10%.
Splenectomy performed for a hematologic disorder, such as thalassemia, hereditary spherocytosis, or lymphoma, appears to carry a higher risk than splenectomy performed as a result of trauma. A major contributing factor is the frequent existence of splenic implants or accessory spleens in traumatized patients, although accessory spleens can also be seen as a developmental anomaly.
Preventative strategies for OPSI fall into 3 major categories: education, immunoprophylaxis, and chemoprophylaxis.
As previously mentioned, education represents a mandatory strategy in the prevention of OPSI. Asplenic patients should be encouraged to wear a Medi-Alert (Pinellas Park, Fla/Henderson, Nev) bracelet and carry a wallet card explaining their lack of a spleen. Patients should also be aware of the need to notify their physician in the event of an acute febrile illness, especially if it is associated with rigors or systemic symptoms.
Vaccination is also appropriate in the prevention of OPSI. This has best been defined for S pneumoniae. Unfortunately, the most virulent pneumococcal serotypes tend to be the least immunogenic, and evidence indicates that the efficacy of the vaccine is poorest in younger patients, who would be at higher risk. However, under ideal conditions in a healthy, immunocompetent host, the vaccine offers a 70% protection rate.
The pneumococcal vaccine should be administered at least 2 weeks before an elective splenectomy. If the time frame is not practical, the patient should be immunized as soon as possible after recovery and before discharge from the hospital or, at the latest, 24 hours following the procedure.
Most authorities recommend antibiotic prophylaxis for asplenic children, especially for the first 2 years after splenectomy. Some investigators advocate continuing chemoprophylaxis in children for at least 5 years or until age 21 years. However, the value of this approach in older children or adults has never been adequately evaluated in a clinical trial.
A major concern is antibiotic use in splenectomized patients. Those who have undergone splenectomy should receive antibiotic prophylaxis prior to undergoing procedures associated with a risk of transient or sustained bacteremia. Antibiotics should cover encapsulated organisms and organisms likely to be found at the operative site.
The usual postoperative activity restrictions imposed on a patient who has undergone a laparotomy or laparoscopy also apply to patients after a laparoscopic splenectomy.
Patients with uncorrected splenomegaly should be counseled to refrain from contact sports or activities that would predispose them to blunt abdominal trauma. Examples include skydiving, horseback riding, soccer, football, and ice hockey. These restrictions reduce the likelihood that blunt injury will lead to splenic rupture and uncontrolled hemorrhage.
The goals of pharmacotherapy in cases of splenomegaly are to reduce mortality and prevent complications. Recall that in the absence of a functional spleen, patients have a defect in bacterial clearance due to impaired opsonization. In particular, these patients are at risk for OPSI due to infection with encapsulated organisms such as H influenzae, N meningitidis, and S pneumoniae.
As previously mentioned, all patients scheduled for elective splenectomy (either diagnostic or therapeutic) should receive a pneumococcal vaccine.
Clinical Context: This vaccine contains capsular polysaccharides of 23 pneumococcal types that together account for 98% of pneumococcal disease isolates.
Clinical Context: This vaccine contains capsular polysaccharide antigens (groups A, C, Y, and W-135) of N meningitidis. It may be used to prevent and control outbreaks of serogroup C meningococcal disease, according to guidelines from the US Centers for Disease Control and Prevention (CDC). The vaccine induces the formation of bactericidal antibodies to meningococcal antigens. It is used for active immunization against invasive meningococcal disease caused by inclusive serogroups. The vaccine induces antibody response for serogroup A in individuals as young as 3 months, but it is poorly immunogenic for serogroup C in recipients younger than 18-24 months.
Clinical Context: This vaccine is used for the routine immunization of children against invasive diseases caused by H influenzae type B. It decreases nasopharyngeal colonization. The CDC Advisory Committee on Immunization Practices has recommended that all children receive a conjugate vaccine licensed for infant use at age 2 months.
Vaccines aid in the generation of an anamnestic response to invasion with the target organism.
Clinical Context: Cefotaxime (adult dose of 2 g IV q8h; pediatric dose of 25-50 mg/kg IV q6h) is a third-generation cephalosporin with excellent in vitro activity against GBS and E coli and other gram-negative enteric bacilli. It attains good concentrations in serum and cerebrospinal fluid (CSF). Concern exists that emergence of drug-resistant gram-negative bacteria may occur at a more rapid rate with cefotaxime than with traditional penicillin and aminoglycoside coverage. Cefotaxime is ineffective against Listeria and enterococci; use it in combination with ampicillin.
Clinical Context: Ceftriaxone (adult dose of 2 g IV q12-24h; pediatric dose of 50 mg/kg IV q12h) is a third-generation cephalosporin with broad-spectrum gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Clinical Context: Vancomycin is a bactericidal agent effective against most aerobic and anaerobic gram-positive cocci and bacilli. It is especially important in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) and is recommended when coagulase-negative staphylococcal sepsis is suspected.
The diagnostic workup should never delay the use of empiric therapy. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Possible choices of empiric antimicrobial agents include cefotaxime and ceftriaxone. Unfortunately, some penicillin-resistant pneumococcal isolates are also resistant to cephalosporins. If such resistance is suggested, consider using vancomycin.