Shelley E. Crary
The spleen is the largest lymphoid organ in the body and plays a vital role in hematologic functions as well as in the defense of the body against invading pathogens.
ANATOMY OF THE SPLEEN
The spleen has two major compartments: the white pulp (which serves the immunologic functions) and the red pulp (the area where blood is filtered). A marginal zone separates the red and white pulp and functions primarily for presentation and processing of antigens.
FUNCTIONS OF THE SPLEEN
About 30% of the circulating platelet mass is sequestered within the spleen. In cases of splenomegaly, a higher volume of blood may become trapped (see “Hypersplenism/Asplenia,” below).
Throughout the second trimester, the spleen plays an active role in hematopoiesis. At birth, little to no splenic hematopoiesis continues.
RED BLOOD CELL CLEARANCE
Due to the unique structure and harsh environment of the spleen’s red pulp, it plays a key role in the removal or culling of aged or damaged red cells from the circulation.
A unique function of the spleen is to selectively remove intraerythrocyte inclusions while allowing the intact red cell to reenter the circulation.
Young reticulocytes generally spend their first few days sequestered in the spleen where they are remodeled as surface area is reduced, unnecessary cytoplasmic organelles and surface adhesion molecules are removed, and the membrane surface becomes more negatively charged.
The spleen is the principal site of phagocytosis of blood-borne antigens and antibody-coated cells. Particulate antigens interact directly with macrophages and other antigen-presenting cells in the periarteriolar lymphoid sheaths. Microorganisms, particularly encapsulated bacteria, are also removed by the splenic macrophages. When antibody-coated cells, including red cells and platelets, pass through the spleen, they may also undergo phagocytosis by macrophages.1
The spleen also produces antibodies after splenic macrophages present blood-borne antigens to the lymphocytes in the white pulp. In the absence of a spleen, an individual will be susceptible to overwhelming sepsis from primarily encapsulated bacteria such as Streptococcus pneumoniae or Haemophilus influenzae type b (see below).
PHYSICAL ASSESSMENT OF SPLENIC SIZE
Although the normal spleen is usually not palpable on physical exam, the splenic tip may be felt in approximately 3% to 5% of normal children and adolescents.2 As the spleen enlarges, it moves downward, and the lower pole may cross the midline toward the right lower quadrant. Palpation of the spleen with the patient in the supine position should begin in the right lower quadrant of the abdomen and should move diagonally to the left upper quadrant. This method will ensure that the examiner does not overlook a massively enlarged spleen.
APPROACH TO SPLENOMEGALY
Mild splenomegaly may occur in many diseases in which there is an abundant immune response (eg, infectious mononucleosis, cytomegalovirus, or subacute bacterial endocarditis). It is also frequently seen in individuals with chronic hemolysis (eg, hereditary spherocytosis, sickle cell disease, thalassemia intermedia or major, or pyruvate kinase deficiency). See Table 440-1 for additional causes of splenomegaly.
In general, the term hypersplenism describes a tetrad of (1) splenomegaly, (2) any combination of cytopenias, (3) compensatory bone marrow hyperplasia, and (4) improvement after splenectomy. Hypersplenism most commonly is associated with congestive splenomegaly resulting from pooling of blood in the enlarged spleen. The degree of cytopenia varies greatly, and in the case of congestive splenomegaly, the blood cells may be released from the spleen in times of need; therefore, these patients are not at an increased risk of bleeding or infection. Occasionally, however, hypersplenism results in marked destruction of the red cells and platelets so that splenectomy may be indicated.
Assessing Splenic Function
Several hematologic changes occur following splenectomy or in patients with congenital or acquired hyposplenism and can be diagnostic. Howell-Jolly bodies (intracellular nuclear remnants) become apparent in peripheral red blood cells and can be visualized under light microscopy on a routine blood smear. Red cell surface “pits” are not cleared following splenectomy or in patients with functional asplenia. Therefore, an elevated pit count, or percentage of red cells with pits, is a sensitive and specific marker of hyposplenia. However, visualization requires specialized optical contrast microscopy not readily available in clinical laboratories. Technetium-99m-sulfur colloid or technetium-99m-labeled heat-damaged red cell spleen scans may also be used to evaluate for the presence or absence of a functioning spleen as well as to document the location of any accessory splenic tissue.
MEDICAL CONDITIONS ASSOCIATED WITH HYPOSPLENISM
The most common medical condition associated with functional hyposplenism is sickle cell disease. Children with sickle cell anemia develop this complication during infancy and early childhood because of alterations in splenic circulation caused by intrasplenic sickling.
Table 440-1. Causes of Splenomegaly
Hyposplenism has also been described in a variety of immunologic and autoimmune disorders (see Table 440-2). Some of these diseases have been reported to be accompanied by an increased risk of bacterial sepsis and are associated with circulating Howell-Jolly bodies and pitted erythrocytes.
Table 440-2. Medical Causes of Asplenia or Hyposplenia
Indications for splenectomy can be conveniently divided into medical (hematologic) and surgical categories. Medical indications include congenital hemolytic anemias, such as hereditary spherocytosis or immune thrombocytopenic purpura. Splenectomy is often indicated in these conditions since the intrinsically abnormal or antibody-coated red blood cells or platelets are prematurely destroyed by the spleen. In storage diseases such as Gaucher disease, massive splenomegaly may develop and become a mechanical burden.
Total splenectomy is generally performed via an open laparotomy; however, laparoscopic techniques are gaining popularity and may be suitable when the spleen is not massively enlarged. Partial splenectomy is also a feasible alternative in some patients; however, the benefit of this procedure (control of the primary condition as well as preservation of splenic phagocytic and immunologic functions) remains controversial.1
CONSEQUENCES OF HYPOSPLENIA/ASPLENIA
The most concerning complication of functional hyposplenism or splenectomy is the risk of bacterial sepsis. Bacteremia in an asplenic host may evolve rapidly into fatal sepsis, sometimes referred to as overwhelming postsplenectomy infection (OPSI) syndrome. Encapsulated organisms including S pneumoniae, H influenza type b, and Neisseria meningitidis are the primary organisms responsible for OPSI. Asplenic patients also appear to be at increased risk of serious infections with Bartonella bacilliformis. The incidence of OPSI varies according to the underlying condition associated with the hyposplenism or for which splenectomy was performed, with patients with sickle cell disease or malignancy at greatest apparent risk. Children younger than 5 years of age appear at highest risk, and the risk is thought to decrease as the interval following splenectomy increases.1 Nonetheless, reports of postsplenectomy sepsis have occurred in individuals many decades following splenectomy, so asplenic individuals likely remain at risk of bacterial infections for life. No studies, however, have evaluated the risk of OPSI in the present era of routine vaccination with heptavalent pneumococcal conjugate vaccine.
Splenectomy or functional asplenia may also be associated with an increased risk of thrombotic events and pulmonary arterial hypertension.
MANAGEMENT OF CHILDREN WITH ASPLENIA/HYPOSPLENISM
Prophylactic therapy with oral penicillin twice daily or an equivalent antibiotic is strongly recommended for infants or young children who have hyposplenia or asplenia.11 In a prospective double-blind trial of sickle cell disease patients less than 3 years old with functional hyposplenia, oral penicillin prophylaxis was shown to reduce the incidence of bacteremia by 84%.12 A second controlled study showed no significant benefit of penicillin prophylaxis after 5 years of age.13 The emergence of penicillin-resistant pneumococci may reduce the effectiveness of penicillin prophylaxis.
Children with asplenia or splenic dysfunction should be immunized with vaccines against S pneumoniae, H influenzae type b, and N meningitidis. The 23-valent pneumococcal polysaccha-ride vaccine is currently recommended for all children with anatomic or functional asplenia at 24 months of age, with a second dose given 3 to 5 years later. The heptavalent pneumococcal conjugate vaccine is immunogenic in infants and should be given according to recommended vaccination schedules. The conjugate H influenzae type b vaccine has virtually eliminated infections caused by this pathogen. Current recommendations also include vaccinating children with anatomic or functional asplenia who are older than age 2 years with the tetravalent meningococcal polysaccharide or conjugate vaccine, depending on age. If a child requires an elective splenectomy, these immunizations should be given at least 2 weeks in advance of surgery if feasible, but are also effective when given after splenectomy.14,15
Parents of children with splenic dysfunction must be educated to regard significant febrile illnesses (≥ 101.5°F) as signaling a potentially life-threatening situation that mandates prompt evaluation by a physician. After a blood culture has been obtained, a parenteral broad-spectrum antibiotic, currently a third-generation cephalosporin, should be administered.
Special Precautions in Children with Enlarged Spleens
Acutely enlarged spleens that are not protected by the rib cage (eg, as in infectious mononucleosis) are at increased risk of rupture following splenic trauma. Children with massive or acute splenomegaly should avoid contact sports and other physical activities associated with significant risk of abdominal injury.16 The risk of splenic rupture following trauma in patients with chronic, moderately enlarged spleens (eg, hereditary spherocytosis) is not well-established.