Splenomegaly

Eichner et al proposed an early taxonomy for the pathophyisiology of splenomegaly as follows[6] :

• Immune response work hypertrophy
• Red blood cell (RBC) work hypertrophy
• Congestive splenomegaly
• Infiltrative splenomegaly
• Neoplastic splenomegaly
• Miscellaneous

Immune response work hypertrophy

Acute enlargement of the spleen due to various infections or inflammatory processes 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 subacute bacterial endocarditis, lupus, and Felty syndrome, and from viral infections such as Epstein-Barr virus–induced mononucleosis.

Red blood cell work hypertrophy

A high rate of removal of abnormal blood cells from the circulation (either cells with intrinsic defects or cells coated with antibody) is the usual source of RBC work hypertrophy. This occurs in thalassemia major, hereditary spherocytosis, and pyruvate kinase deficiency. Thalassemia major has the additional mechanism of leading to splenomegaly due to extramedullary hematopoiesis as a result of intramedullary hemolysis. 

Congestive splenomegaly

Cirrhosis with portal hypertension, splenic vein occlusion (thrombosis), or chronic heart failure (CHF) with increased venous pressure causes congestive splenomegaly. In patients receiving oxaliplatin-based chemotherapy, splenomegaly may result from hepatic sinusoidal obstructive syndrome caused by the chemotherapy; use of bevacizumab may reduce the splenomegaly in these cases.[7]

Infiltrative splenomegaly

Infiltrative splenomegaly is the result of engorgement of macrophages with indigestible materials. It may be seen in conditions such as sarcoidosis, Gaucher disease, and amyloidosis. 

Neoplastic splenomegaly

Hematologic neoplasms make up the bulk of cancer-related causes of splenomegaly. This category includes both lymphoproliferative (eg, lymphomas, leukemias) as well as myeloproliferative (eg, chronic myeloid leukemia, primary myeloid fibrosis, essential thrombocythemia, polycythemia vera) neoplasms. Rarely, sarcoma can occur in the spleen, or primary solid tumors can metastasize to the spleen.  

Miscellaneous

Additional causes of splenomegaly include trauma, splenic cysts, and hemangiomas. 

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 increase as the abscess enlarges. This is a relatively uncommon, but important, process to recognize and treat.

Acute splenic sequestration crisis (ASSC) is a major cause of morbididty and mortality in children with sickle cell disease and other hereditary hemolytic anemias. ASSC is characterized by sudden enlargement of the spleen due to trapping of a significant proportion of the blood volume, rapid drop in the hematocrit with hypovolemia, and thrombocytopenia. ASSC is rare in adults with sickle cel disease or beta thalassemia, despite the frequent presence of spleneomegaly in this population. Infection and high-altitude exposure are known precipitating factors for ASSC.[8]

Many of the mechanisms leading to splenomegaly are exaggerated forms of normal splenic function. Although a wide variety of diseases are associated with enlargement of the spleen, the following six etiologies of splenomegaly are considered primary:

• Immune response work hypertrophy - Such as in subacute bacterial endocarditis or infectious mononucleosis

• RBC destruction work hypertrophy - Such as in hereditary spherocytosis or thalassemia major

• Congestive - Such as in splenic vein thrombosis, portal hypertension, or Banti disease

• Infiltrative - Such as in sarcoidosis and some neoplasms

• Neoplastic - Lymphoproliferative disorders such as chronic lymphocytic leukemia, hairy cell leukemia, and lymphomas, as well as myeloproliferative disorders including chronic myeloid leukemia, primary myeloid fibrosis, essential thrombocythemia, and polycythemia vera

• Miscellaneous - Such as trauma, cysts, hemangiomas, abscesses (see the images below), certain drugs (ie RhoGAM)

This patient has a splenic abscess due to pneumococcal bacteremia. Note that the massively enlarged spleen is readily visible, with minimal retraction in the left upper quadrant.

Resected specimen from the patient in the previous image. Note the discrete abscesses adjacent to normal parenchyma.

In the United States, one large series reported a palpable spleen in 2% of patients and another in 5.6% of patients.[9] Tropical splenomegaly syndrome occurs most often in persons indigenous to the malarial belt of tropical Africa and in visitors to that region.

Race-, Sex-, and Age-related demographics

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, which 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.

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

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 vary widely 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 more likely to be exposed to emergent operative splenectomy and its attendant risks. 

Patients with splenomegaly need education with regard to decreasing their risk of splenic trauma and rupture. 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.

For patient education information, see Enlarged Spleen.

Patients whose splenomegaly has led to splenectomy require education regarding the signs and symptoms of postsplenectomy sepsis. Education represents a mandatory strategy in the prevention of overwhelming postsplenectomy infection. Asplenic patients should be encouraged to wear a medical alert bracelet and carry a wallet card explaining their lack of a spleen. These 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. Prompt antibiotic therapy may be lifesaving.

The most common complaint in patients with splenomegaly is mild, vague, abdominal discomfort. Patients may also experience pain,which may be referred to the left shoulder. Increased abdominal girth is possible but less common. Early satiety from gastric displacement occurs with massive splenomegaly. Patients may complain of discomfort when lying supine or on their right side. Associated symptoms or signs are typically related to the underlying disorder and may include the following:

• Febrile illness (infectious)
• Pallor, dyspnea, bruising, and/or petechiae (hemolytic process)
• History of liver disease (congestive)
• Weight loss, constitutional symptoms (neoplastic)
• Pancreatitis (splenic vein thrombosis) ^[10]
• Alcoholism, hepatitis (cirrhosis) ^{[11, 12]}

Family history should be reviewed to disclose relevant hereditary diseases, such as hemolytic anemias.

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 healthy 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.[9]

The physical examination includes both percussion and palpation techniques. Percussion is performed with the patient in the supine position. If the spleen is not enlarged, tympany to percussion will be present in the area known as Traube's space (defined by the left sternal border, the costal margin, and the lower border of the 9th ribs), due to the normal presence of the air-filled gastrum. Dullness to percussion in that area indicates displacement with non-hollow viscus, typically the spleen.

For palpation, the examiner applies light pressure with the fingertips in the space below the costal margin, with the patient first in the supine position and then in the right lateral decubitus position with the hips flexed. Gentle pressure to the right posterior rib cage can also help bring the spleen into contact with the examiner's fingers, as can the use of the reverse Trendelenburg position; the latter is especially helpful in patients with morbid obesity. Perform palpation during both inspiration and expiration. 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, left lower quadrant, or 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 extends into the pelvis.

Additional physical exam findings to note include:

• Signs of cirrhosis - Eg, asterixis, jaundice, telangiectasias, gynecomastia, caput medusa, ascites
• Heart murmur - Endocarditis or congestive failure
• Jaundice
• Lymphadenopathy
• Scleral icterus - Spherocytosis or cirrhosis
• Evidence of skeletal hypertrophy
• Petechiae - Any other bleeding manifestation secondary to thrombocytopenia

Initial evaluation of the patient with splenomegaly should include the following:

• Complete blood cell count (CBC) with differential
• Evaluation of peripheral blood smear for red blood cell (RBC) morphology and signs of myeloproliferative disorders or underlying bone marrow disorder
• Liver function testing, including coagulation studies
• Hepatitis B and C testing
• Lactate dehydrogenase (LDH)
• Urinalysis
• Chest x-ray

Those studies can help identify various causes of splenomegaly, such as sickle cell disease, spherocytosis, and other hereditary hemolytic anemias. If the differential count reveals a lymphocyte predominance, flow cytometry should be performed. Results consistent with neoplasm may prompt fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) testing for BCR-ABL or Jak 2. Depending on the apparent etiology, bone marrow biopsy may be needed.

If this initial workup does not yield a diagnosis, then the clinician can evaluate for an underlying disease state with the following, based on clinical appropriateness:

• Biopsy of suspicious lymph nodes
• Bone marrow aspirate and biopsy to evaluate for myeloproliferative and lymphoproliferative disease as well as disseminated infection
• Liver biopsy
• Flow cytometry of the peripheral blood, to assess for an indolent lymphocytic leukemia (eg, hairy cell leukemia, chronic lymphocytic leukemia) that may be causing splenic enlargement
• Erythrocyte sedimentation rate (ESR) to screen for subacute/non-fulminant infectious syndromes

Clinically detected splenomegaly is confirmed and quantified using imaging studies. Ultrasonography is a noninvasive, highly sensitive, and specific imaging technique for the evaluation of splenic size. Point-of-care ultrasonography significantly improved the sensitivity of physical examination alone in diagnosing splenomegaly in a prospective study of 39 adult hospitalized patients.[14]

On imaging studies, the upper limit of normal splenic size is frequently defined as a craniocaudal measurement of 11-13 cm. However, because of wide variations in splenic 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.

The term hypersplenism describes some of the sequelae that are often observed with splenomegaly. Criteria for a diagnosis of hypersplenism include the following:

• Splenomegaly
• Anemia, leukopenia, thrombocytopenia, or combinations thereof
• Cellular bone marrow
• Improvement after splenectomy

The mechanisms for those blood count abnormalities are as follows:

• Anemia - The anemia observed in splenomegaly results from sequestration and hemodilution.
• Leukopenia - Increased destruction or sequestration of leukocytes causes the leukopenia observed in splenomegaly. Leukopenia is closely related to neutropenia. Neutropenia (absolute neutrophil count [ANC] < 1800/μL) is the result of an increase in the marginated granulocyte pool, a portion of which is located in the spleen (see the Absolute Neutrophil Count calculator). Sequestration may also play a role in the genesis of neutropenia.
• Thrombocytopenia -  Increased splenic platelet pooling is the primary cause of the thrombocytopenia of hypersplenism. Normally, approximately 30% of the total platelet mass exists as an exchangeable pool in the spleen; 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.

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

Splenectomy may be considered in certain individuals to determine the etiology of splenomegaly, though early diagnostic splenectomy is rarely indicated.[15, 16, 17, 18, 19, 20]  The need for a diagnosis must be carefully weighed against the morbidity associated with the asplenic state and should be pursued only after other means of diagnosis have been exhausted. Splenectomy is typically performed laparoscopically; even supramassive spleens can be removed by laparoscopic surgery with minimal morbidity.[19, 21] Splenectomy is therapeutic in individuals with severe pancytopenia due to splenomegaly.

Splenic biopsy

Splenic biopsy may be performed in specialized institutions, though is rarely indicated. Severe bleeding is a frequent complication that limits the usefulness of this procedure. Mosquera-Klinger et al reported that endoscopic ultrasound (EUS)–guided fine needle aspiration proved a safe and effective technique for obtaining splenic biopsy samples. In their review of EUS-guided splenic punctures in 15 patients, no patient experienced immediate or delayed complications related to the procedure.[22]

Histologic evaluation

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.

Computed tomography

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 Hounsfield units (H). Normally, the liver and spleen densities are within 25 H on dynamic contrast-enhanced CT scans.[23]

In general, the spleen can be considered enlarged if its craniocaudal length is more than 10 cm 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.

Liver-spleen colloid scan

For spleen scanning, erythrocytes are labeled with chromium-51 (51Cr) , mercury-197 (197Hg), rubidium-81 (81Rb), or technetium-99m (99mTc), and the cells are altered by treatment with heat, antibody, chemicals, or metal ions so that the spleen will sequester them after infusion. A splenic length of greater than 14 cm is considered 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.

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 occasionally indicated to help control or stage the underlying disease in cases of splenomegaly. The most common indications for  therapeutic splenectomy include hereditary spherocytosis, immune thrombocytopenia (ITP), or autoimmune hemolysis where the splenomegaly is refractory to front line therapy and causing significant discomfort due to massive splenomegaly or complicated hypersplenism.

In addition, splenectomy enables pathologic diagnosis in lymphoproliferative disorders such as splenic marginal zone lymphoma or hairy cell leukemia. A review by Naples et al of splenectomy for idiopathic splenomegaly in 68 patients found that final surgical pathology of the removed spleen provided a definitive diagnosis for 44 patients (64.7%). Of those, 34 patients (50%) had an underlying malignancy, of which more than half were splenic marginal zone lymphoma.[20]  Of note, splenic marginal zone lymphoma secondary to hepatitis C can often resolve with treatment of the viral hepatitis, and cases not associated with hepatitis C can be treated with rituximab monotherapy thereby sparing the complications of splenectomy. 

Splenectomy is also indicated for the treatment of chronic, severe hypersplenism refractory to upfront medical therapy.[24] This can occur in conditions such as the following:

• Hairy cell leukemia
• Felty syndrome
• Primary myelofibrosis (agnogenic myeloid metaplasia)
• Thalassemia major
• Gaucher disease
• Hemodialysis splenomegaly
• Splenic vein thrombosis ^[10]

Treatment of splenic sequestration involves conservative management with blood transfusions/exchange transfusions to reduce the number of sickled red blood cells, or splenectomy. Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in sickle cell disease.[25]

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 in these patients

Low-dose radiotherapy has been used as palliative care for splenomegaly in patients with hematologic disorders such as primary myelofibrosis.[26] Bruns et al reported that low-dose splenic irradiation produced hematologic response and long-term relief of splenic pain in four of five patients with symptomatic congestive splenomegaly.[27]

In a review by Zaorsky et al that included 766 courses of splenic irradiation for 486 patients from 1960 to 2016, the most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders. Splenic irradiation produced a partial or complete response in 85-90% of patients; 30% were retreated within 6-12months.[28]

Although the most common splenic irradiation regimen was 10Gy in 1Gy fractions over 2 weeks, these authors concluded that lower doses (eg, 5Gy in 5 fractions) might be as effective as higher doses, as they found no correlation between the biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement.[28]

Inpatient care

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

Outpatient care of patients with splenomegaly consists of three 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

Patients undergoing elective splenectomy for splenomegaly may develop significant hemorrhaging during their operation if controlling the splenic hilum proves difficult. Such patients may require abdominal packing and transfer to a tertiary center with personnel who have expertise in angioembolization and splenic resection for splenomegaly.[3]

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.

Consultations

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.

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.

As the majority of cases of splenomegaly are secondary to some underlying disorder, it is incumbent on clinicians to first attempt mitigation of the splenomegaly via treatment of those primary disorders. Broad examples of treatment include the following:

• Chemotherapy for hematologic malignancies
• Antibiotics for infection (with the exception of infection associated with a splenic abscess, which requires surgical intervention)
• Immunosuppression for autoimmune disorders such as rheumatoid arthritis
• Disease-modifying therapy for severe heart failure
• Genetic interventions for congenital abnormalities

Important recent developments in mitigating splenomegaly include the use of the JAK2 inhibitor ruxolitinib in primary myelofibrosis, which results in rapid and pronounced reduction in spleen size.[29] Eliglustat, an oral substrate reduction therapy, significantly improved spleen volume, hemoglobin level, liver volume, and platelet count in 40 previously untreated adults with Gaucher disease type 1 in a randomized, double-blind, placebo-controlled study.[30]

All patients scheduled for elective splenectomy (either diagnostic or therapeutic) should receive the 23-valent polysaccharide pneumococcal vaccine, menigococcal vaccine, and ​H. influenzae vaccine. Ideally vaccination should occur weeks prior to surgery if it is elective. Antibiotic prophylaxis wtih a penicillin is also indicated particularly in younger children less than 5 years old as they are at higher risk for severe sepsis after splenectomy.

The vast majority of splenectomies are performed using laparoscopic techniques. It is important to remember that splenectomy should largely be reserved for only after non-surgical approaches to mitigating the primary disorder causing the splenomegaly have been utilized and in the event of  emergent traumatic situations where splenic sparing/salvage techniques cannot be safely employed. 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.)[31, 32]

Intraoperative photograph of a laparoscopic splenectomy being taken down using the hanging-pedicle technique. The tip of the spleen is visualized in the background, whereas the stapler is detailed in the foreground across a segment of the pedicle.

Massive splenomegaly does not preclude splenectomy through a minimally invasive approach. This photograph depicts a fragmented 3.2 kg (7.05 lb) spleen after removal via a hand-assisted laparoscopic technique.

A portion of a massive spleen is extracted via hand-assisted laparoscopy.

A reactive thrombocytosis following splenectomy is common though is not clearly associated with an increased risk of VTE. One cohort calculated the incidence of postsplenectomy secondary thrombocytosis at ~30%.[33]  This reactive thrombocytosis typically peaks in 2-3 weeks but can persist for months to years. [34] One prospective cohort study evaluating thrombosis risk after abdominal surgery found splenectomized patients to be at a higher rate of postoperative VTE than other abdominal surgeries however there was no statistical correlation between presence of reactive thrombocytosis and VTE. [35]

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.

Prevention

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.

Preprocedure prophylaxis

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 goals of pharmacotherapy in cases of splenomegaly are to reduce mortality and prevent complications. 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 overwhelming postsplenectomy infection (OPSI) due to infection with encapsulated organisms such as Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.[36]  Appropriate vaccination is indicated.[37]

Patients with clinical evidence of OPSI require empirical antibiotics. Please see separate guidelines for treatment of infections in the splenectomized patient.[38, 39]

Class Summary

Patients should ideally undergo the following prophylactic vaccinations against encapsulated organisms prior to splenectomy.

Vaccines should be administered at least 14 days prior to scheduled splenectomy. If indicated, multiple vaccines can be given during the same visit at different anatomic sites usually. If it is not possible to vaccinate patients preoperatively, immunizations can be given after the 14th postoperative day. Vaccinations should be delayed for at least 3 months in patients undergoing immunosuppressive chemotherapy or radiotherapy.

Pneumococcal vaccine (Pneumovax 23)

This vaccine contains capsular polysaccharides of 23 pneumococcal types that together account for 98% of pneumococcal disease isolates.

Meningitis group A C Y and W-135 vaccine (Menomune-A/C/Y/W-135)

This vaccine contains capsular polysaccharide antigens (groups A, C, Y, and W-135) of Neisseria 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 quadrivalent meningococcal polysaccharide vaccine (Menomune, MPSV4) has been approved by the US Food and Drug Administration for individuals  over 56 years of age; however, this vaccine was discontinued in 2017. A quadrivalent meningococcal conjugate vaccine (Menactra or Menveo) is preferred by the United States Advisory Committee on Immunization Practices (ACIP) for individuals in this age group who are expected to require revaccination .

Meningococcal serogroup B vaccine is also recommended.

Haemophilus influenza type b conjugate vaccine (ActHIB, Hiberix, PedvaxHIB)

This vaccine is also used for the routine immunization of children against invasive diseases caused by Haemophilus influenzae type B. 

Class Summary

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.

Ceftriaxone (Rocephin)

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.