eMedicine Specialties > Pediatrics: General Medicine > Hematology

Splenomegaly

Mundeep K Kainth, DO, Resident Physician, Department of Pediatrics, The Children's Hospital at Albany Medical Center
Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Associate Professor of Pediatric Hematology-Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute; Richard H Sills, MD, Professor of Pediatrics, Upstate Medical University

Updated: Sep 4, 2008

Introduction

Background

Splenomegaly in childhood is generally first suspected upon physical examination. One third of newborns and 10% of children may normally have a palpable spleen. The tip of the normal, palpable spleen is soft, smooth, nontender and less than 1-2 cm below the left costal margin. A pathologically enlarged spleen is often firm, may have an abnormal surface, and is frequently associated with signs and symptoms of the underlying disease. When any of these features are noted, or if the tip of the spleen is enlarged more than 1-2 cm below the costal margin, further evaluation should be considered.¹

Pathophysiology

Anatomy

The spleen is the largest lymphoid organ in the body. The spleen and the lymph nodes are the major components of the mononuclear-phagocyte system (MPS). They serve as filters that remove damaged cells, microorganisms, and particulate matter and deliver antigens to the immune system. The MPS, originally called the reticuloendothelial system, consists of fixed phagocytic cells in different organs. These phagocytes locally interact with lymphocytes and play an essential role in the recognition of antigens and their interaction with immunocompetent cells.²

The splenic tissue consists of red and white pulp lying in a capsule. Blood enters the spleen through the splenic artery, a branch of the celiac artery. It then travels into the smaller arterioles and approaches the white pulp. The white pulp, rich in T and B lymphocytes, receives plasma for antigen processing. Splenic macrophages efficiently ingest these antigens and deliver them to the immunocompetent cells of the spleen for antibody production and stimulation of T-lymphocyte immune responses. The remaining hemoconcentrated blood continues into the contiguous red pulp, the sinuses and cords of which are also lined with macrophages.

The red pulp forms most of the splenic tissue and consists of splenic cords, the circulation of which is designated as open because no well-defined endothelial lining is present. To exit the cords, blood must pass through 1-µm to 5-µm slits in this fenestrated basement membrane to reach the venous sinusoids. The circulation through the cords is slow and congested. This delay provides prolonged exposure of blood cells, bacteria, and particulate matter to the dense mononuclear-phagocyte elements in the red pulp.

After reaching the sinuses, blood from the red pulp empties into the splenic vein, which joins the superior mesenteric vein to form the hepatic portal vein. Because no valves are present in the splenic venous system, the pressure in the splenic vein reflects the pressure in the portal vein.

Function

One of the primary functions of the spleen is the filtration of defective cells. Erythrocytes slowly pass through the hypoxic and acidotic environment of the splenic cords and then squeeze through narrow slits into the sinusoids. Although healthy erythrocytes readily accomplish this passage, aged and abnormal red cells, such as spherocytes and sickle cells, remain behind to be ingested by the macrophages lining the cords. Fc receptors on splenic macrophages also bind to IgG antibody-coated erythrocytes or platelets, which are mainly cleared by the spleen.

The spleen is also critical for clearing circulating, particularly encapsulated, bacteria. The amorphous polysaccharide coat of encapsulated bacteria greatly impairs their clearance in the absence of antibody, and only the spleen's highly efficient phagocytic cords can effectively clear them. The splenic white pulp processes these intravenous antigens and produces antibody that, during subsequent exposures, allows for efficient clearance by the rest of the MPS.

The splenic cords are uniquely capable of removing erythrocytic inclusions, such as nuclear remnants (ie, Howell-Jolly bodies) or precipitated globin (ie, Heinz bodies), without destroying the cell. The spleen also serves as a reservoir for platelets and produces blood components (extramedullary hematopoiesis) if the bone marrow is unable to meet demands.³

Frequency

United States

A 1-cm to 2-cm splenic tip is palpable in 30% of full-term neonates and in as many as 10% of healthy children. Approximately 3% of healthy college freshmen have palpable spleens. Initial and follow-up studies confirm that these college freshmen are not at high risk for subsequent serious disease.^4,5,1

International

Malaria, schistosomiasis, and other infections in endemic areas are frequent causes of splenomegaly.⁶

In malaria-endemic areas, the prevalence of splenomegaly (ie, spleen rate) is a measure of malaria exposure. In hyperendemic areas (eg, Papua New Guinea), the spleen rate in children exceeds 50%.⁷ Such hyperendemic areas have a prevalence of massive splenomegaly (hyperreactive malarial splenomegaly) of 1-2% in children.⁸

Mortality/Morbidity

Splenic rupture may occur in acute splenomegaly associated with infectious mononucleosis. The incidence is 1:1000, and it usually occurs in the first 3 weeks of illness.⁹

Splenectomy is uncommonly performed in children with splenomegaly. Nevertheless, should it be clinically indicated, the overall risk of postsplenectomy sepsis is approximately 2%, with increased incidence and mortality in young children.^10,11

Hypersplenism is the occurrence of thrombocytopenia, and occasionally leukopenia and anemia, in the context of significant splenomegaly.¹² The cytopenias are usually mild but may contribute to overall morbidity.¹³

Race

Specific causes of splenomegaly are most common in certain racial groups. Examples include splenic sequestration as a complication of sickle cell disease in patients of African or Mediterranean ancestry and noncirrhotic portal fibrosis in patients of Iranian, South Asian, or Japanese ancestry.¹⁴

Age

The etiology of splenomegaly varies with age. For example, splenic sequestration in sickle cell disease occurs early in life, before the splenic involution that ultimately occurs in most patients with sickle cell disease.

Clinical

History

Despite the extensive differential diagnoses of splenomegaly, careful history taking and physical examination, along with a CBC count and liver function tests, often help in narrowing the list of possible causes. The history should include attention to the following important areas, as listed below.¹⁵

• Chief symptoms
  • Acute or chronic nature
  • Painful or asymptomatic manifestation
  • Ingestion of hepatotoxic agents resulting in hepatitis or portal hypertension
  • Abdominal trauma that may cause splenic hematoma
  • Acute illness such as hepatitis, mononucleosis, or malaria
  • Diarrhea (eg, salmonellosis, inflammatory bowel disease)
  • Bone pain, fever, malaise, lethargy, or bruising (eg, associated with leukemia)
  • Weight loss, fevers, night sweats (eg, associated with Hodgkin disease)
  • Jaundice
• Medical history
  • Complicated neonatal period (eg, sepsis, hypotension)
  • Umbilical catheter thrombosis
  • Hyperbilirubinemia, anemia (eg, due to hereditary spherocytosis or hemolysis)
  • Heart disease (eg, congestive heart failure)
  • Past surgeries (eg, leading to infection, thrombosis, portal hypertension)
  • Transfusions (eg, resulting in hepatitis)
  • Hepatitis
  • Abdominal trauma (possibly resulting in splenic pseudocyst)
  • Travel (possible presence of malaria, leishmaniasis, schistosomiasis, or trypanosomiasis)
  • Sexual behavior (possible presence of hepatitis, cytomegalovirus [CMV], or human immunodeficiency virus [HIV])
  • Known blood disorder (eg, sickle cell disease, hereditary spherocytosis)
• Family history
  • Anemia, cholecystectomy (eg, due to hemolytic anemia–associated gallstones)
  • Splenectomy (eg, due to hemolytic anemia)
  • Mediterranean ethnicity (increased incidence of thalassemia and glucose-6-phosphate dehydrogenase [G6PD] deficiency)
  • African ethnicity (increased incidence of sickle cell anemia, G6PD deficiency, and hereditary pyropoikilocytosis)
  • Ashkenazi Jewish ethnicity (increased incidence of Gaucher disease and Niemann-Pick disease)
  • Northern European ethnicity (increased incidence of pyruvate kinase deficiency and hereditary spherocytosis)
  • Asian ethnicity (increased incidence of G6PD)
  • South Asian ethnicity (increased incidence of portal hypertension secondary to noncirrhotic portal fibrosis)

Physical

The patient should be examined in the supine or right lateral decubitus position. The spleen is best palpated with the clinician kneeling on the patient's right side and by palpating the left upper quadrant of the abdomen with the right hand.

Palpation should start just above the pubis and move toward the left upper quadrant to find the medial border of the spleen. The examiner usually palpates the spleen by feeling its inferolateral margins. If the enlarged tip of the spleen is below the examiner's hands, he or she often misses it. Likewise, light pressure should be used with small children, because the spleen can easily be pushed out of the way without the clinician feeling its edge. At times, the superior medial edge of the spleen is more readily palpated than the inferior margin.

Percussion over the left lateral areas of the lower ribs may reveal splenomegaly that is not evident upon palpation.^16,17,18 This procedure is particularly helpful in a crying child in whom splenic palpation is difficult. It is similarly helpful in children and adolescents who are obese. A normal-sized liver and spleen may also become palpable if pulmonary pathology is causing hyperinflation of the lungs (pseudosplenomegaly). The spleen is occasionally confused with the left lobe of the liver or with a tumor in the left upper quadrant (eg, Wilms tumor, neuroblastoma). The characteristic downward movement of the spleen with inspiration and its relatively flat surface and shape can help in differentiating it from other masses of the left upper quadrant. Important features on physical examination are as follows:¹⁵

• General findings - Failure to thrive, ill-appearing (eg, in the presence of malignancy, chronic hemolysis, chronic infection, metabolic disease, liver disease, or inflammatory disease)
• Dermal findings
  • Pallor (eg, due to anemia, which may indicate hemolysis, bone marrow infiltration, or hypersplenism)
  • Petechiae, purpura (eg, due to thrombocytopenia, which may indicate bone marrow failure, autoimmune disorder, or hypersplenism)
  • Jaundice (eg, due to hemolytic anemia or liver disease)
  • Itching, pruritus (eg, due to liver dysfunction, Hodgkin lymphoma)
  • Rashes (eg, due to acute and chronic infections, systemic lupus erythematosus, rheumatoid arthritis, infective endocarditis, histiocytoses, or hemangiomata)
  • Eczematous rash (eg, due to Langerhans cell histiocytosis or immunodeficiency)
• Head, eyes, ears, nose, and throat findings
  • Icterus (eg, due to hemolytic anemia or liver dysfunction)
  • Cherry red retinal spots, cloudy corneas (eg, due to lipid storage diseases)
• Respiratory and cardiovascular findings
  • Dyspnea, fatigue (eg, due to anemia or congestive heart failure)
  • New murmur (eg, due to infective endocarditis)
• GI findings
  • Abdominal tenderness (eg, due to gallstones, hepatitis, trauma, or acute splenomegaly)
  • Distention, prominent abdominal veins, ascites (eg, due to liver disease)
  • Enlarged liver with a firm, knobby texture
• Musculoskeletal findings
  • Joint pain (eg, due to systemic lupus erythematosus, rheumatoid arthritis, or autoimmune inflammatory diseases)
  • Poor bone growth (eg, due to storage diseases or osteopetrosis)
  • Bone pain (eg, due to leukemia or Gaucher disease)
• Neurologic findings
  • Poor vision (eg, due to osteopetrosis)
  • Uveitis, iritis (eg, due to sarcoidosis or rheumatoid arthritis)
  • Loss of developmental milestones (eg, due to storage diseases, chronic infection, or immunodeficiency)

Causes

Despite the numerous causes of splenomegaly (see Differentials), the spleen is rarely the primary site of disease.

• The most common mechanism of splenomegaly in children is hyperplasia of the MPS, which can be categorized as excessive antigenic stimulation (ie, infection), disorders of immunoregulation (ie, autoimmune disorders), or excessive destruction of abnormal blood cells (ie, hemolysis).^2,19
  • Excessive antigenic stimulation due to infection is the cause of most cases of splenomegaly in children. Viral infections are the most frequent culprits, and the associated splenomegaly is usually transient and only mild to moderate in severity. Although Epstein-Barr virus (EBV) and CMV are well known causes of splenomegaly, the most typical viral illnesses of childhood are the most frequent causes.
  • Other common infectious etiologies include bacterial, protozoal, and fungal infections. In endemic areas, malaria and schistosomiasis are routine causes of splenomegaly. Concomitant generalized lymphadenopathy is common in many of these infectious etiologies.
  • Inflammation due to collagen vascular diseases, such as juvenile rheumatoid arthritis, and increased destruction of blood cells from hemolytic anemias are relatively uncommon, but clinically significant, causes of splenomegaly.
  • Splenomegaly can be a presenting sign of neoplasia. One half of children with acute lymphoblastic leukemia have splenomegaly. Splenomegaly is also a frequent finding in non-Hodgkin lymphoma, Hodgkin disease, and acute or chronic myeloblastic leukemia. Metastatic involvement of the spleen, which is uncommon in children, is most often caused by neuroblastoma. Histiocytes can infiltrate the spleen; Langerhans cell histiocytosis and other rare histiocytic disorders are usually the cause of this condition.
  • Obstructed venous blood flow of intrahepatic or extrahepatic etiology can cause splenomegaly. The most common causes include portal vein thrombosis, hepatic cirrhosis, and congestive heart failure. Children with extrahepatic portal venous obstruction, such as cavernous transformation, often present with splenomegaly as the primary manifestation of their disease.
  • Many storage diseases result in splenomegaly. In Gaucher or Niemann-Pick disease, splenomegaly is often the first clinical manifestation. Splenomegaly is the result of the accumulation of abnormal lipids in splenic macrophages.
  • After trauma, palpable subcapsular hematomas may develop in the spleen, which may eventually develop into clinically palpable pseudocysts. Patients with congenital splenic cysts usually present with asymptomatic splenomegaly.
  • Although normally found only during the first 6 months of life, extramedullary hematopoiesis may occur in diseases associated with intense demand on the bone marrow for cell production. Thalassemia major, osteopetrosis, and idiopathic myelofibrosis are examples of this rare cause of splenomegaly.
• Hypersplenism is a clinical syndrome in which cytopenias result from excessive splenic function, which occurs as the spleen and its MPS tissues hypertrophy. The pathologic action of the spleen, ie, the reduction of circulating blood elements, has been attributed to 4 possible mechanisms: excessive splenic phagocytic activity, splenic production of an antibody that results in the destruction of hematopoietic cells, overactivity of splenic function, and sequestration.²⁰ In patients with cirrhosis, abnormalities of cytokine production may contribute to the cytopenias noted.¹³
  • As the spleen enlarges, it can sequester erythrocytes, leukocytes, and platelets, resulting in mild-to-moderate decreases in some or all of these cell lines. Severe reductions in cell counts are unusual and should prompt a search for alternative etiologies.
  • Venous obstruction is the most common cause of hypersplenism. Any increase in portal pressure is reflected in the splenic venous sinuses. This impairs blood flow out of the cords and results in the sequestration of blood cells and hypersplenism. Hypersplenism in children is most frequently caused by portal hypertension. Extrahepatic venous obstruction from portal vein thrombosis is the most common cause of increased portal pressures. In extrahepatic venous obstruction, hepatic function is normal. Intrahepatic venous obstruction is usually due to cirrhosis.
  • Portal hypertension usually increases flow through minor collateral vessels between the portal circulation and the systemic circulation. Portal hypertension can result in recognizable dilatation of the superficial abdominal veins and esophageal varices. Patients with these varices may present with sudden and catastrophic GI hemorrhage.
• Splenic sequestration crisis is a specific form of acute hypersplenism in young children with sickle cell anemia.²⁰
  • Children less than 6 years old can develop rapid splenic sequestration and splenomegaly with the consumption of large volumes of erythrocytes. They present with sudden weakness, dyspnea, and left-sided abdominal pain in addition to splenomegaly.
  • Splenic sequestration is an emergency. Rapid death from hypovolemic shock can result.
  • Treatment consists of fluids and erythrocyte transfusions. To prevent recurrences, splenectomy may be indicated. In most patients with sickle cell disease, the spleen eventually involutes, and sequestration is no longer possible.

Differential Diagnoses

Other Problems to Be Considered

Hepatitic cirrhosis
Portal hypertension
Cavernous transformation of the portal vein
Chronic myelocytic leukemia
Hereditary spherocytosis
Autoimmune hemolytic anemia
Chediak-Higashi syndrome
Immunodeficiency disorders
Niemann-Pick disease
Lipid storage diseases
Langerhans cell histiocytosis
Hematomas
Pseudocysts

Workup

Laboratory Studies

• Splenomegaly is usually the result of systemic disease and not the result of primary splenic disease. Therefore, diagnostic studies are not directed at the spleen itself. Instead, they are oriented at diagnosing disease states that result in splenomegaly. The most useful initial laboratory tests include the CBC count with differential, peripheral blood smears, and liver function tests.¹⁹
• The CBC count may be revealing.
  • Pancytopenia may be present because of bone marrow infiltration and hypersplenism.
  • The WBC count may reveal atypical lymphocytes (eg, neutropenia, or neutrophilia (eg, due to infection or leukemia).
  • Hemoglobin concentrations, RBC smears, and reticulocyte counts may reveal anemia, abnormal erythrocyte morphology, reticulocytosis (eg, due to hemolysis), or malarial parasites.
  • The platelet count may indicate thrombocytopenia due to decreased production (eg, due to bone marrow infiltration), increased destruction (eg, due to immunologic causes, drug reactions, or viral infections), or sequestration or hypersplenism.
• Liver function tests may demonstrate the following abnormal values:
  • Hypoalbuminemia, prolonged prothrombin time, indirect and direct hyperbilirubinemia (eg, due to liver dysfunction)
  • Isolated indirect hyperbilirubinemia (eg, due to hemolysis)
  • Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (eg, due to liver damage)
  • Elevated gamma glutamyltransferase (GGT) and alkaline phosphatase levels (eg, due to biliary obstruction)
• Obtain an antinuclear antibody titer to screen for systemic lupus erythematosus.
• Measure immunoglobulin levels, neutrophil function, and T-cell subclasses (e.g., due to immunodeficiency).
• Obtain viral-antibody titers to detect EBV, CMV, Toxoplasma gondii, and HIV.
• Cultures may reveal bacterial, fungal, or other infections.
• Examine the bone marrow to screen for leukemia, lymphoma, storage diseases, and disseminated fungal or mycobacteria infections.

Imaging Studies

• Ultrasonography can confirm the presence of the enlarged spleen or space-occupying lesions (eg, cyst, abscess), provide accurate dimensions, and help in distinguishing between splenic enlargement and other causes of a left subchondral mass (eg, kidney). Confirming or excluding splenomegaly in patients with obesity, in whom palpation can be very challenging, is useful. Often, a single craniocaudal measurement is used to report spleen size; awareness of the normal values for age is important.²¹ Collateral blood vessels develop secondary to portal hypertension, and reversal of portal vein blood flow direction may be visualized with Doppler ultrasonography.
• CT scanning and MRI of the left upper quadrant can help in further clarifying abnormalities in size and shape and in defining parenchymal pathology. The "splenic index" is the product of the length, width, and thickness of the spleen and has limited value.²²
• Radioisotopic scanning with a technetium-99m sulfur colloid (spleen scan) can provide functional information about the spleen that other radiologic studies do not provide.⁶

Histologic Findings

• Biopsy of the spleen may be performed. The results are of limited value in common diagnoses, and the procedure is associated with a notable risk, particularly bleeding.
• The diagnosis is occasionally recognized after splenectomy.
• Examples of disease that might be examined with biopsy include infiltrative diseases, such as Gaucher disease, Niemann-Pick disease, amyloidosis, Tangier disease, and glycogen-storage diseases. Other diseases that may be diagnosed with splenic tissue include Langerhans cell histiocytosis, sarcoidosis, systemic lupus erythematosus, and Hodgkin disease. In Hodgkin disease, biopsy samples were often obtained in the past with staging laparotomy, but this is no longer performed because of improved imaging and systemic therapy.

Treatment

Medical Care

Because splenomegaly is usually the result of a systemic disease, the primary goal is treatment of the underlying process. In certain circumstances, splenectomy may be the therapy of choice for symptoms or complications caused by the enlarged organ. However, because of the risk of overwhelming sepsis in children who are asplenic, the risks and benefits must be carefully weighed when splenectomy is being considered.^10,11

• The new PCV7 conjugated pneumococcal vaccine and the older PPV23 polyvalent pneumococcal vaccines and the Haemophilus influenzae vaccine should be administered to all children who are asplenic and to those about to undergo splenectomy. The polyvalent pneumococcal vaccine is effective only if the patient is aged 2 years or older. Meningococcal vaccine, MCV4, is often administered to these patients in this age group as well. To maximize antibody formation, vaccines should be administered at least 10 days before splenectomy.²³
• Daily penicillin is recommended to prevent pneumococcal septicemia in asplenic children younger than 5 years. Antibiotic prophylaxis is often administered for several years after splenectomy in patients older than 5 years, but the role of prophylaxis in these children is less well documented than it is in others.
• In patients with homozygous sickle cell anemia or sickle beta-zero thalassemia, oral penicillin prophylaxis should be started when the diagnosis is established. This therapy should be administered until at least age 5 years. The role of penicillin prophylaxis in patients with hemoglobin sickle cell disease is controversial. Patients with sickle beta+ thalassemia do not appear to need penicillin prophylaxis.
• Febrile illnesses in asplenic children should be approached as potentially life-threatening events and evaluated thoroughly, with a low threshold for treatment with intravenous antibiotics that cover Streptococcus pneumoniae and H influenzae. The increasing prevalence of drug-resistant S pneumoniae and the decreasing incidence of H influenzae infections are complicating factors in determining the optimal choice of antibiotics.

Surgical Care

Splenic trauma is the most common indication for splenectomy, although attempts at splenic preservation are increasingly important. Nonsurgical management for splenic trauma has success rates of 52-98%, with failure usually occurring in the first 96 hours. Splenic cysts, tumors, and vascular lesions may also require surgical removal. Whenever possible, splenic tissue is preserved to decrease the risk of septicemia, but total splenectomy is occasionally necessary.^24,25

• Splenectomy can cure hypersplenism but is not usually indicated because the secondary cytopenias rarely cause serious problems. However, in patients with portal hypertension, vascular shunts may be necessary to prevent esophageal variceal bleeding.
• Splenectomy may be helpful in improving cytopenias in several medical conditions, including congenital anemias (eg, hereditary spherocytosis, elliptocytosis) and autoimmune disorders (eg, immune thrombocytopenic purpura, autoimmune hemolytic anemia, hypersplenism). In thalassemia major, splenectomy may initially decrease the transfusion requirements caused by hypersplenism. However, the benefit must be carefully weighed against the risk of sepsis.
• In Gaucher disease, splenectomy may be necessary when the mechanical strain of the enlarged spleen requires intervention.
• Splenectomy may be indicated in children with sickle cell anemia and a history of splenic sequestration crisis in order to prevent recurrences of the crisis.
• As part of exploratory laparotomy, splenectomy was once an important component of staging of Hodgkin disease. This procedure is rarely used because of improvements in imaging modalities, the high risk of postsplenectomy sepsis, and the increased use of chemotherapy in patients, which allows treatment decisions to be made on the basis of radiologic evaluation alone. Furthermore, data suggest that splenectomy increases the risk of second malignancy in patients treated for Hodgkin disease.

Consultations

A pediatric hematologist and/or oncologist is the usual consultant when the cause of splenomegaly is not obvious or when a primary hematologic or oncologic disorder is suspected.

Activity

• According to the American Academy of Pediatrics and the Council of Sports Medicine and Fitness, children with acutely enlarged spleens should avoid contact, collision, or limited-contact sports.²³  Viral-related splenomegaly rarely lasts longer than 2 months.
• The duration for which contact restriction should persist after acute infectious mononucleosis remains uncertain. In the absence of trauma the incidence of splenic rupture is approximately 1:1000, usually occurring in the first 3 weeks of illness. No evidence-based guidelines are available. More conservative suggestions recommend that children with infectious mononucleosis and resolution of splenomegaly noted on examination have 3 weeks of rest with a 4-week graded return to activity. However, it has also been suggested that contact sports can resume as soon as 4 weeks after onset of illness.²⁶
• Even with large spleens, disorders associated with chronic splenomegaly have reduced splenic friability with minimal risk of rupture. In children with chronically enlarged spleens, decision to restrict activity should be made on a case-by-case basis.²⁷

Medication

The choice of therapy depends on the specific etiology of the splenomegaly.

Vaccines

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

With the increased problem of penicillin resistance in S pneumoniae, prevention by using the conjugated pneumococcal vaccine in children or by using the unconjugated 23-valent pneumococcal vaccine in adults is mandatory. Likewise, immunizations with the conjugated H influenzae type B and meningococcal A and C vaccines are essential. Vaccines are administered at least 10 days before splenectomy.

Pneumococcal 7-valent conjugate vaccine (Prevnar)

Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. These 7 serotypes responsible for >80% of invasive pneumococcal disease in children <6 y in the United States and account for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance.
Customary age for first dose is 2 mo, but can be administered as young as 6 wk. Preferred sites for IM injection are anterolateral aspect of thigh in infants or deltoid muscle of upper arm in toddlers and young children. Do not inject in gluteal area or areas with a major nerve trunk or blood vessel.
Number of 0.5-mL doses is 3 for infants aged 7-11 mo (4 wk apart; third dose after first birthday), 2 for those aged 12-23 mo (2 mo apart), and 1 for those aged 2-5 y.
Minor illnesses (eg, mild upper respiratory tract infection with or without low-grade fever) are not generally contraindications.

Dosing

Adult

Not established

Pediatric

0.5 mL IM; 3 doses q2mo; fourth dose of 0.5 mL at 12-15 mo of age, or at 2 mo or later after third dose; recommended dosing interval is 4-8 wk

Interactions

Immunosuppressive agents (immunosuppressive doses of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may decrease effects; may increase effects of anticoagulant therapy; globulin preparations may interfere with immune response and reduce efficacy (do not administer within 3 mo of vaccination)

Contraindications

Documented hypersensitivity to any component or diphtheria toxoid; severe or moderate febrile illness; thrombocytopenia or coagulation disorder contraindicating IM injection (unless benefits outweigh risks)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

For IM use only, do not administer IV under any circumstances; take special care to prevent injection into or near blood vessel or nerve; caution in patients with possible history of latex sensitivity (packaging contains dry natural rubber); does not replace 23-valent pneumococcal polysaccharide vaccination in children >24 mo of age with sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised; caution in coagulation disorders

Pneumococcal vaccine (Pneumovax-23)

Polyvalent vaccine used for prophylaxis against infection from S pneumoniae. Used in populations at increased risk of pneumococcal pneumonia (ie, >55 y, chronic infection, asplenia, immunocompromise).

Dosing

Adult

0.5 mL IM/SC once

Pediatric

<2 years: Contraindicated (antibody response poor in this age group)
>2 years: 0.5 mL IM/SC; repeat dose after 3-5 y in high-risk children (eg, those with functional or anatomic asplenia or conditions associated with rapid antibody decline after initial vaccination)

Interactions

Immunosuppressive agents (eg, large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may reduce effectiveness; therapy with immunoglobulin preparations likely to block active immunity induced; withhold for 3 mo after discontinuation of immunoglobulin therapy

Contraindications

Documented hypersensitivity to any component or thimerosal; severe or even moderate febrile illness; age <2 y; thrombocytopenia or any coagulation disorder that contraindicates IM injection unless potential benefit clearly outweighs risk

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Arthralgia, fever, urticaria, and Guillain-Barré syndrome (rare)

Meningococcal vaccine (Menomune A/C/Y/W-135, Menactra)

Capsular polysaccharide antigens (groups A, C, Y, and W-135) of Neisseria meningitidis. For active immunization against invasive meningococcal disease caused by inclusive serogroups. May be used to prevent and control outbreaks of serogroup C meningococcal disease according to Centers for Disease Control and Prevention (CDC) guidelines.
Routine vaccination recommended for high-risk groups (eg, patients with deficiencies in late complement components [C3, C5-C-9], functional or actual asplenia, or laboratory or industrial exposure to N meningitidis aerosols; travelers or residents of hyperendemic areas).
Vaccine induces antibody response for serogroup A in individuals as young as 3 mo, but poorly immunogenic for serogroup C in recipients <18-24 mo.

Dosing

Adult

0.5 mL SC

Pediatric

<2 years: Not established
>2 years: Administer as in adults

Interactions

Coadministration with whole-cell pertussis or whole-cell typhoid vaccines may increase endotoxin content; immunosuppressive drugs may interfere with immune response

Contraindications

Documented hypersensitivity; acute illness (avoid); IV/IM/ID administration

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Asplenic patients with lymphoid tumors who receive chemotherapy or irradiation respond poorly; for information concerning geographic areas where vaccination is recommended, see the Meningococcal Conjugate Vaccine: ACIP Recommendation page from the CDC Advisory Committee on Immunization Practices (ACIP); spontaneous reports of Guillain-Barré syndrome recently (2005) reported with Menactra

H influenzae B vaccine (PedvaxHIB, HibTITER, ActHIB)

For routine immunization of children against invasive diseases caused by H influenzae type B by decreasing nasopharyngeal colonization. The CDC ACIP recommends that all children receive one of the conjugate vaccines licensed for use in infants beginning routinely at age 2 mo.

Dosing

Adult

Not indicated

Pediatric

Regimens vary depending on product.
Example:
HibTITER:
2-6 months: 0.5 mL IM q2mo for 3 doses
7-11 months: 0.5 mL IM q2mo for 2 doses in previously unvaccinated children
12-14 months: 0.5 mL IM once in previously unvaccinated children
15-71 months: 0.5 mL IM once in previously unvaccinated children
Booster dose: 0.5 mL at age 15 mo or at least 2 mo after last dose of immunization series; booster dose unnecessary in children vaccinated for the first time at age 15-71 mo

Interactions

Immunoglobulins given within 1 mo or concurrently with immunosuppressants may inhibit full immunologic response

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Delay immunization if febrile illness evident; may cause erythema, swelling, or tenderness; cause-and-effect relationship with Guillain-Barré syndrome after vaccination not established

Antibiotics

Daily antibiotic prophylaxis with penicillin is recommended to prevent pneumococcal septicemia.

Penicillin VK (V-Cillin K, Veetids, Pen-Vee K)

Inhibits biosynthesis of cell-wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations reached. Most effective during stage of active multiplication. Low concentrations produce bacteriostatic effects.

Dosing

Adult

Pediatric

<5 years: 125 mg PO bid
>5 years: 250 mg PO bid

Interactions

Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, decreasing in effectiveness of penicillins when administered concurrently

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal impairment

Follow-up

Further Inpatient Care

• Further care depends on the specific etiology of the splenomegaly and, rarely, on the splenomegaly itself.
• The development of hypersplenism with resulting anemia, leukopenia, and/or thrombocytopenia can be severe enough to cause serious problems, although this is not usually the case.

Complications

• Splenic rupture may occur in acute splenomegaly associated with infectious mononucleosis. The incidence is 1:1000, and it usually occurs in the first 3 weeks of illness.⁹ Therefore, the American Academy of Pediatrics Council on Sports Medicine and Fitness has recommended that children with acute splenomegaly restrict their participation in sport.²⁷  Disorders associated with chronic splenomegaly do not have the same splenic friability and risk of rupture.^28,27  
• Splenectomy is uncommonly performed in children with splenomegaly. Nevertheless, should it be clinically indicated, the overall risk of postsplenectomy sepsis is approximately 2%, with increased incidence and mortality in young children.^10,11
• Hypersplenism is the occurrence of thrombocytopenia, and occasionally leukopenia and anemia, in the context of significant splenomegaly.¹² The thrombocytopenia is usually mild, and, in liver cirrhosis, the underlying mechanism may involve mechanical pooling and cytokine changes.^29,13

Prognosis

• The prognosis depends on the specific etiology of the splenomegaly.

Patient Education

• Risks of traumatic rupture of a large and/or fragile spleen must be discussed.
• Other education depends on identifying the specific etiology of the splenomegaly.

Miscellaneous

Medicolegal Pitfalls

• Recommended restrictions on physical activity for children with acute splenomegaly need to be enforced, even for those with relatively modest splenomegaly, because patients with mononucleosis have friable spleens that may rupture, with catastrophic effect.
• When patients have chronic splenomegaly, follow the American Academy of Pediatrics guidelines and assess the degree of splenomegaly, its underlying cause, and the involvement of the patient's family and others who provide supervision, before approving the patient's participation in contact or collision sports.
• If splenectomy is medically indicated, ensure that appropriate immunizations are given prior to the procedure, and the family is appropriately counseled on care of the asplenic child.

References

1. Arkles LB, Gill GD, Molan MP. A palpable spleen is not necessarily enlarged or pathological. Med J Aust. Jul 7 1986;145(1):15-7. [Medline].

2. Sills RH. Splenic function: physiology and splenic hypofunction. Crit Rev Oncol Hematol. 1987;7(1):1-36. [Medline].

3. Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. Aug 2005;5(8):606-16. [Medline].

4. McIntyre OR, Ebaugh FG. Palpable spleens in college freshmen. Ann Intern Med. Feb 1967;66(2):301-6. [Medline].

5. Ebaugh FG, McIntyre OR. Palpable spleens: ten-year follow-up. Ann Intern Med. Jan 1979;90(1):130-1. [Medline].

6. Ancliff P, Hann I. Splenomegaly. In: Sills RH, ed. Practical Algorithms in Pediatric Hematology and Oncology. Basel, Switzerland: Karger; 2003:50-1.

7. Genton B, al-Yaman F, Beck HP, et al. The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity. Ann Trop Med Parasitol. Aug 1995;89(4):359-76. [Medline].

8. Pitney WR. The tropical splenomegaly syndrome. Trans R Soc Trop Med Hyg. 1968;62(5):717-28. [Medline].

9. Farley DR, Zietlow SP, Bannon MP, Farnell MB. Spontaneous rupture of the spleen due to infectious mononucleosis. Mayo Clin Proc. Sep 1992;67(9):846-53. [Medline].

10. Castagnola E, Fioredda F. Prevention of life-threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes. Eur J Haematol. Nov 2003;71(5):319-26. [Medline].

11. Price VE, Dutta S, Blanchette VS, Butchart S, Kirby M, Langer JC, et al. The prevention and treatment of bacterial infections in children with asplenia or hyposplenia: practice considerations at the Hospital for Sick Children, Toronto. Pediatr Blood Cancer. May 1 2006;46(5):597-603. [Medline].

12. Wilson DB. Acquired platelet defects. In: Nathan DG, Orkin SH, Ginsburg D, Look AT. Nathan and Oski's hematology of infancy and childhood. Vol 2. 6^th ed. Philadelphia, PA: WB Saunders; 2003:1599.

13. Peck-Radosavljevic M. Hypersplenism. Eur J Gastroenterol Hepatol. Apr 2001;13(4):317-23. [Medline].

14. Sarin SK, Kapoor D. Non-cirrhotic portal fibrosis: current concepts and management. J Gastroenterol Hepatol. May 2002;17(5):526-34. [Medline].

15. Tunnessen WW Jr. Splenomegaly. In: Roberts K, Tunnessen W, eds. Signs and Symptoms in Pediatrics. 3^rd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 1999:475-83.

16. Nixon RK Jr. The detection of splenomegaly by percussion. N Engl J Med. Jan 28 1954;250(4):166-7. [Medline].

17. Castell DO. The spleen percussion sign. A useful diagnostic technique. Ann Intern Med. Dec 1967;67(6):1265-7. [Medline].

18. Grover SA, Barkun AN, Sackett DL. The rational clinical examination. Does this patient have splenomegaly?. JAMA. Nov 10 1993;270(18):2218-21. [Medline].

19. Pochedly C, Sills RH, Schwartz AD, eds. Disorders of the Spleen: Pathophysiology and Management. New York, NY: Marcel Dekker; 1989.

20. Kinney TR, Ware RE, Schultz WH, Filston HC. Long-term management of splenic sequestration in children with sickle cell disease. J Pediatr. Aug 1990;117(2 Pt 1):194-9. [Medline].

21. Robertson F, Leander P, Ekberg O. Radiology of the spleen. Eur Radiol. 2001;11(1):80-95. [Medline].

22. Schlesinger AE, Hildebolt CF, Siegel MJ, Pilgrim TK. Splenic volume in children: simplified estimation at CT. Radiology. Nov 1994;193(2):578-80. [Medline].

23. AAP. Immunocompromised children. In: Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26^th ed. Elk Grove, IL: American Academy of Pediatrics; 2003:69-81.

24. Lane PA. The spleen in children. Curr Opin Pediatr. Feb 1995;7(1):36-41. [Medline].

25. Rice HE, Oldham KT, Hillery CA, Skinner MA, O'Hara SM, Ware RE. Clinical and hematologic benefits of partial splenectomy for congenital hemolytic anemias in children. Ann Surg. Feb 2003;237(2):281-8. [Medline].

26. Eichner ER. Sports medicine pearls and pitfalls--defending the spleen: return to play after infectious mononucleosis. Curr Sports Med Rep. Apr 2007;6(2):68-9. [Medline].

27. Rice SG; American Academy of Pediatrics Council on Sports Medicine and Fitness. Medical conditions affecting sports participation. Pediatrics. Apr 2008;121(4):841-8. [Medline].

28. Goddard SL, Chesney AE, Reis MD, et al. Pathological splenic rupture: a rare complication of chronic myelomonocytic leukemia. Am J Hematol. May 2007;82(5):405-8. [Medline].

29. Jandl JH, Aster RH. Increased splenic pooling and the pathogenesis of hypersplenism. Am J Med Sci. Apr 1967;253(4):383-98. [Medline].

30. Goodman J, Newman MI, Chapman WC. Disorders of the spleen. In: Greer JP, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. 11^th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2004:1893-909.

31. Shurin SB. Splenomegaly. In: Kliegman R, Nieder M, Super D, et al, eds. Practical Strategies in Pediatric Diagnosis and Therapy. Philadelphia, PA: WB Saunders; 1996:352-9.

Keywords

splenomegaly, splenic enlargement, enlarged spleen, palpable spleen, hypersplenism, splenic enlargement, splenectomy, mononuclear-phagocyte system, MPS, malaria, schistosomiasis, hyperreactive malarial splenomegaly, splenic rupture, noncirrhotic portal fibrosis, sickle cell disease, hepatitis, portal hypertension, abdominal trauma, splenic hematoma, diarrhea, salmonellosis, leukemia, Hodgkin disease, jaundice, sepsis, hypotension, umbilical catheter thrombosis, anemia, leishmaniasis, trypanosomiasis, splenic pseudocyst, cytomegalovirus, human immunodeficiency virus, HIV, hemolytic anemia–associated gallstones, hemolytic anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency, G6PD deficiency, hereditary pyropoikilocytosis, pyruvate kinase deficiency, hereditary spherocytosis

Contributor Information and Disclosures

Author

Mundeep K Kainth, DO, Resident Physician, Department of Pediatrics, The Children's Hospital at Albany Medical Center
Mundeep K Kainth, DO is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Associate Professor of Pediatric Hematology-Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute
Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Royal College of Physicians of the United Kingdom
Disclosure: Nothing to disclose.

Richard H Sills, MD, Professor of Pediatrics, Upstate Medical University
Richard H Sills, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology and Idaho Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Wayne Hioe, MD, to the development and writing of this article.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)