Pediatric Asplenia

Updated: Oct 19, 2016
  • Author: Mudra Kumar, MD, MRCP, FAAP; Chief Editor: Harumi Jyonouchi, MD  more...
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Overview

Background

Asplenia is the absence of spleen and/or its functions. Abnormalities of the spleen may be classified on a pattern-oriented approach, based on splenic imaging. [1] These include anomalies of the following:

  • Shape (clefts, notches, lobules)
  • Location (wandering spleen)
  • Number (asplenia, polysplenia)
  • Size (splenomegaly, atrophy)
  • Solitary lesions (cysts, lymphangiomas, hemangiomas, hamartomas)
  • Multiple lesions (trauma, infections, neoplasms, storage disorders)
  • Diffuse disease (infarction, heavy metal deposition, peliosis)

Absence of splenic tissue can be total (congenital asplenia) or partial (hypoplastic) from birth.

Loss of splenic tissue due to surgical removal may occur later in life as a result of trauma that causes rupture of the organ. The spleen may be removed in other conditions (eg, hemoglobinopathies) to improve the red cell life expectancy. Removal of the spleen may be undertaken as a result of being involved in a neoplastic processor as a staging procedure in some cancers. Occasionally, the spleen may be removed to address the sheer mass effect of a massive enlargement (such as in storage disorders), which can cause mass effects.

Autosplenectomy is the process where the spleen loses its function due to multiple and repeated infarctive episodes, as in sickle hemoglobinopathies. See the image below.

Peripheral blood smear shows Howell-Jolly (HJ) bod Peripheral blood smear shows Howell-Jolly (HJ) bodies in RBCs.
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Pathophysiology

Absent or defective splenic function is associated with a high risk of fulminant bacterial infections, especially with encapsulated bacteria. 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 opsonize bacteria. Thus the spleen serves both to "tag bacteria for destruction" and plays a role in the actual destruction of the bacteria through phagocytosis. The spleen is also involved in the functional maturation of antibodies and is a significant reservoir for both B and T lymphocytes. The number 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 may reflect the loss of the spleen as a reservoir rather than a direct T-cell abnormality.

The spleen plays an important role in granulocyte homeostasis also by influencing the elimination of senescent cells and regulatory effects on granulocyte renewal in the bone marrow. A potentially elevated proinflammatory status of granulocytes is noted, as suggested by intensity pf CD11b,c and TREM-1 in congenital asplenia. [2, 3] Another study indicates that the T lymphocyte subset in congenital aplasia may be associated with presence of CD4(+) T cells that express the "naïve" phenotype, possible failure in CD8(+) cytotoxic effectors differentiation and tendency to the proinflammatory status of cells, low interleukin (IL) 10 expression, and suboptimal lymphocyte responses to mitogenic stimulation. [4]

The red pulp of the spleen is designed as an efficient filtering system that serves as an important scavenger. The spleen participates in the destruction of all 3 blood elements (erythrocytes, leukocytes, and platelets) when they reach senescence. In the process of removing 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 red cells (spherocytes, poikilocytes) and intracellular inclusions (Heinz bodies, Howell Jolly bodies). These functions are known as culling and pitting, respectively, and loss of these functions results in the persistence of abnormal red cells and inclusions in the peripheral smear in patients with absent splenic function.

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.

The most common and serious are rapidly progressive, overwhelming, and often fatal infections due to gram positive encapsulated organisms. Streptococcus pneumonia is most commonly reported but Haemophilus influenzae type b, and Neisseria meningitides are also common. [5, 6, 7] Other organisms include Staphylococcus aureus, Salmonella species, and Pseudomonas aeruginosa.

In infants younger than 6 months, gram-negative enteric organisms such as Klebsiella species and Escherichia coli are the most common pathogens. Multiple bacterial infections have been reported in the same patient. [6]

Unusual complications of infections may be seen in asplenic patients, especially those with congenital heart disease. Endocarditis due to Bordetella holmesii was reported in a patient with asplenia and prosthetic mitral valve. Bacteremia due to Bordetella holmesii was reported in 4 cases with asplenia.

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.

Persistent and significant thrombocytosis associated with asplenia. This may contribute to the development of thromboembolic complications, especially in those with significant congenital cardiac abnormalities.

Isolated (congenital) absence of spleen is thought to be extremely rare, although a French report suggests that it may be more common than previously thought. An autosomal dominant mode of inheritance has been suggested. Recently the discovery of genes responsible for isolated congenital asplenia was reported.

Most cases of congenital asplenia (or polysplenia) are associated with abnormalities of other organ systems and result from interference in the establishment of normal right-left symmetry during embryogenesis (heterotaxy syndrome, 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.

Both asplenia and polysplenia are associated with congenital cardiac anomalies. These anomalies are more common, severe, and generally complex in asplenia. These include endocardial cushion defects, atrioventricular canal defects pulmonary atresia or pulmonary stenosis, transposition of the great vessels, total anomalous pulmonary venous return, and a double-outlet right ventricle. Cyanotic heart diseases, 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, multiple spleens are found along the greater curvature of the stomach is on the right side. 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.

Congenital asplenia is most often found in association with other developmental anomalies. The most common is 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.

Pearson syndrome (pancreatic insufficiency, sideroblastic anemia) 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). 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.

Asplenia was identified in 4 family members with autoimmune polyendocrine syndrome type-1. Horseshoe adrenal glands have also been associated with Asplenia syndrome. A patient was reported with Cat eye syndrome with anatomical asplenia.

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. 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 start losing the splenic function in the first year of life and become anatomically asplenic (secondary 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.

Neonates may have suboptimal splenic function.

Additional conditions associated with splenic hypofunction include rheumatologic diseases (systemic lupus erythematous [SLE], rheumatoid arthritis), inflammatory bowel disease, graft versus host disease, and nephrotic syndrome.

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Epidemiology

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 or when relatives of an index case are investigated.

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 have asplenia as part of heterotaxy syndromes, often have increased mortality and morbidity related to extrasplenic abnormalities in neonatal period. However, if they survive past age 1 month, they 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).

Sex

There is male predominance in asplenia syndrome (ie, Ivemark syndrome) is 2:1. Polysplenia syndrome is more predominant in females, whereas asplenia may be more common in males.

Age

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

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