Pediatric Asplenia 

Absent or defective splenic function is associated with a high risk of fulminant bacterial infections, especially with encapsulated bacteria. Asplenia and splenic hypoplasia are terms used to indicate complete or partial lack of splenic tissue. Loss of splenic tissue usually occurs as a result of surgical removal or autosplenectomy (ie, infarction in patients with sickle hemoglobinopathies). In certain conditions, patients may lack normal splenic function despite having spleens that are normal in size or even enlarged; this is called functional asplenia and is also associated with risk of fulminant bacterial sepsis. Congenital splenic anomalies are usually accompanied by abnormalities in other organ systems, especially cardiac abnormalities, but they may occur in isolation.

Patients with polysplenia have multiple spleens, and their splenic function is usually normal, but polysplenia is also frequently associated with congenital cardiac anomalies. Isolated asplenia or hyposplenia is often diagnosed only after the patient has had a serious, fulminant, and often fatal infection. These conditions are extremely difficult to diagnose in the absence of other indicators, and morphologic anomalies of peripheral blood erythrocytes, such as Howell-Jolly (HJ) bodies, may be the only evidence of the presence of a nonfunctional spleen (see the image below and Workup).

Although considered a nonvital organ, and once thought to serve no practical purpose, the spleen is now recognized as an important secondary lymphoid organ in immune defense and as a filter for the bloodstream. In embryonic development, the spleen begins to form as early as 12 days' gestation, along with the splanchnic mesodermal plate; this is one of the processes involved with formation of the asymmetrical left-right axis. In mice that lack critical transcription factors (eg, BAPX1, HOX11), development of the normal left-right axis is disrupted, and no spleen is formed. In humans, the spleen is the site for early hematopoietic development, particularly the development of erythrocytes during the first 4 months' gestation. After birth, the spleen has several important functions as a secondary lymphoid organ and as a reservoir and filter for cells and platelets.

The white pulp of the spleen contains germinal centers, with lymphocytes, plasma cells, and macrophages that help coordinate the immune response and play roles in both innate and adaptive immunity. The spleen has an active role in the production of immunoglobulin M (IgM) antibodies and complement, both of which can be used to opsonize bacteria. In this way, the spleen serves both to "tag bacteria for destruction" and plays a role in the actual destruction of the bacteria through phagocytosis. The spleen also plays a role in the functional maturation of antibodies and is a significant reservoir for both B and T lymphocytes. The percentages of total T cells (CD3) and T helper cells (CD4) and the lymphoproliferative responses to mitogens (concanavalin A, phytohemagglutinin, pokeweed mitogen) may decrease in patients with asplenia; however, these T-cell changes reflect the loss of the spleen as a reservoir rather than a direct T-cell abnormality.

The impaired clearance of opsonized particles, decreased IgM levels, and poor antibody production (especially in response to polysaccharide antigens) contribute to the increased susceptibility of patients with asplenia to serious and often fatal bacterial infections. In infants younger than 6 months, gram-negative enteric organisms such as Klebsiella species and Escherichia coli are the most common pathogens. After age 6 months, Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis may cause fulminant sepsis.

Malaria, babesiosis, and certain viral infections may also be more severe in individuals with asplenia. The younger the patient at the time of splenic function loss, the higher the risk for serious infection.

The red pulp of the spleen is designed as an efficient filtering system that serves as an important scavenger. For example, the spleen participates in the destruction of all 3 blood elements (ie, erythrocytes, leukocytes, and platelets) when they reach senescence. In the process of removing senescent erythrocytes, the splenic macrophages play a critical role in the body’s ability to recycle iron. The spleen also plays an important role in the selective removal of abnormal cells (spherocytes, poikilocytes) and intracellular inclusions (Heinz bodies, HJ bodies). These functions are known as culling and pitting, respectively, and are the basis of the hematologic abnormalities observed in patients with absent splenic function.

Congenital anomalies of the spleen may be isolated, but most cases of asplenia or polysplenia result from interference in the establishment of normal right-left symmetry during embryogenesis (laterality sequences). Congenital asplenia may be viewed as bilateral right-sidedness and is associated with dextrocardia in approximately one third of the cases. Polysplenia may be regarded as bilateral left-sidedness and may be associated with left atrial isomerism.

Congenital cardiac anomalies are more common and are often more severe in asplenia than in polysplenia. The cardiac abnormalities are generally complex and include endocardial cushion defects, pulmonary atresia or pulmonary stenosis, transposition of the great vessels, total anomalous pulmonary venous return, and a double-outlet right ventricle. Similar cardiac defects may be present in both polysplenia and asplenia, but cyanotic heart diseases, including severe atrioventricular canal defects, tend to be more common in asplenia, whereas acyanotic defects, which usually occur with increased pulmonary blood flow, are more common in polysplenia.

In polysplenia, the stomach may be on the right side, and multiple spleens are found along the greater curvature. Absence of the hepatic portion of the inferior vena cava with an azygous venous connection is characteristic. Data regarding splenic competency in polysplenia is scarce, and reports vary from suboptimal to normal function. Accessory spleens should be distinguished from polysplenia. In polysplenia, a normal spleen is absent. Accessory spleens are usually located in the hilus of the normal spleen or in the tail of the pancreas. The accessory splenules are typically small and clinically insignificant but may become hypertrophied in certain situations.

Splenosis is an unusual condition in which trauma or surgery to the spleen can result in transplantation of splenic tissue into other organs or cavities such as the thorax, kidney, or liver. Although it is generally a benign condition, it can radiographically mimic malignancy and result in extensive workup and invasive procedures.^[1]

Asplenia is most often found in association with other anomalies. The most common of these anomalies is the Ivemark syndrome, also referred to as asplenia syndrome, in which visceral heterotaxy is present with bilateral right-sidedness. The right-sided organs are duplicated, and organs that are normally present on the left side are absent. Infants with Ivemark syndrome usually present during the neonatal period with cyanosis and respiratory distress resulting from complex cardiac anomalies. Transposition of the great arteries with pulmonary stenosis (72%) or atresia (88%) and total anomalous venous drainage (72%) are common.

Accompanying malformations may involve the GI system secondary to aberrant mesenteric attachments and renal anomalies. The liver tends to be symmetrical and transverse, and the stomach may be in the midline and hypoplastic. This condition is more common in males than in females, and most patients (79%) die in their first year of life due to cardiovascular complications. A clue to the underlying problems may be obtained by carefully examining radiographs, which may reveal abnormal placement of the cardiac apex, stomach bubble, and liver.

Other associated conditions include Pearson syndrome (pancreatic insufficiency, sideroblastic anemia), which is a mitochondrial disorder associated with splenic atrophy. Asplenia is also present in Stormorken syndrome (thrombocytopenia and miosis). Occasionally, asplenia may be present in Smith-Fineman-Myers syndrome (mental retardation, short stature, cryptorchidism) and ATR-X syndrome (α thalassemia and mental retardation).^[2] Asplenia may be associated with caudal deficiency or cystic disease of the liver, kidney, and pancreas. It has also been reported in association with Fanconi aplastic anemia. Recently, asplenia was identified in 4 family members with autoimmune polyendocrine syndrome type-1.^[3]

Vascular disturbances, including failure of the splenic artery to reach the developing spleen, may be a possible explanation for isolated asplenia. Familial situs abnormalities may be related to chromosome band Xq24-q27.1.^[4] Splenic hypoplasia is a poorly defined and infrequently recognized condition that is usually not associated with other anomalies and may be familial.

Functional asplenia is associated with conditions such as homozygous sickle cell disease, hemoglobin sickle cell disease, and sickle cell hemoglobin (Hb S) β thalassemia. Most children with these hemoglobinopathies are functionally hyposplenic starting in the first year of life and become anatomically asplenic (due to splenic infarction and splenic atrophy) by the second decade of life. The infection risks in these individuals parallel those of patients with asplenia.

Patients who undergo splenectomy because of thalassemia or Hodgkin disease have a higher risk of overwhelming infection than those patients with functional hyposplenia secondary to sickle cell disease. Additional conditions associated with splenic hypofunction include neonatal age, rheumatologic diseases (systemic lupus erythematous [SLE], rheumatoid arthritis), inflammatory bowel disease, graft versus host disease, and nephrotic syndrome.

Patients may also require surgical splenectomy because of traumatic injuries to the spleen or conditions that cause splenic enlargement, such as hereditary spherocytosis or autoimmune lymphoproliferative syndrome (ALPS).

Frequency

United States

The exact incidence of these conditions is not known. Asplenia or polysplenia is present in approximately 3% of neonates with structural heart disease and in 30% of patients who die from cardiac malposition. Isolated asplenia or hyposplenia is probably an underdiagnosed condition that is most often recognized at autopsy.

Mortality/Morbidity

Compared with mortality rates in healthy children, the rate in children with a splenectomy caused by trauma is increased 50-fold, and the rate in patients with sickle cell disease is increased 350-fold.

Neonates with congenital asplenia have high morbidity and mortality rates usually caused by related cardiovascular insufficiency.

Infants who survive past the age of 1 month have a higher risk of dying from sepsis than from associated cardiac disease. Therefore, the early identification of asplenia in infants with congenital heart disease is of paramount importance. To prevent fatal bacterial sepsis, which may be the first manifestation of asplenia in infants with sickle cell disease, routine newborn diagnosis is essential and needs to be followed by preventive measures such as prophylactic antibiotics and vaccinations (see Treatment).^[5]

Sex

The male-to-female predominance in asplenia syndrome (ie, Ivemark syndrome) is 2:1. Polysplenia syndrome is more predominant in females, whereas asplenia is more common in males.

Age

The risk of bacteremia is higher in younger children compared with older children.