eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Asplenia

Joseph C Turbyville, MD, Fellow, Department of Allergy and Immunology, Walter Reed Army Medical Center
Cecilia P Mikita, MD, MPH, Associate Program Director, Allergy-Immunology Fellowship, Chief, Clinical Services, Allergy-Immunology Clinic, Walter Reed Army Medical Center; Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine

Updated: Aug 13, 2008

Introduction

Background

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 fulminant bacterial sepsis risk. 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 Workup).

Pathophysiology

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 with multisystem involvement 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.
 
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-q27.1.³ 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).⁴

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.

Clinical

History

All patients with congenital or acquired asplenia or splenic dysfunction are at significant risk of fulminant bacteremia, especially from encapsulated bacteria. S pneumoniae is the most common pathogen implicated in bacteremia in these patients. Other encapsulated organisms include H influenzae type b, N meningitidis, E coli, Staphylococcus aureus, and other streptococci. Gram-negative bacilli including Salmonella species, Klebsiella species, and Pseudomonas aeruginosa are less common causes of bacteremia in patients with asplenia. These patients are also at risk for malaria and babesiosis.

• Worldwide, most patients with asplenia or hyposplenia have an underlying hemoglobinopathy such as sickle cell disease.
  • Isolated asplenia and polysplenia are commonly associated with significant abnormalities involving other organ systems.
  • An awareness of these associations and syndromes may help in screening the patient for splenic dysfunction.
• The most important clinical indication for the evaluation of splenic function is the presence of complex congenital heart disease. Patients should be evaluated for splenic dysfunction if any of the following are present:
  • Recurrent infection or sepsis, especially with encapsulated organisms
  • Family history of asplenia or polysplenia
  • Cyanotic congenital heart disease or complex cardiac malformations
  • Evidence of visceral heterotaxy or other associated malformations
  • Bilateral trilobed or bilobed lungs on chest radiographs
• In contrast, the presentation of patients with isolated congenital absence or hypoplasia of the spleen may be less dramatic.
  • Children with these conditions may present to the primary caretaker with fever or overwhelming sepsis, or they may even be moribund.
  • Associated cardiovascular, pulmonary, GI, or genitourinary abnormalities may not be present to alert the physician to their underlying immunocompromised state.
• Features such as thrombocytosis, HJ bodies in red cells, and recurrent episodes of invasive infections with encapsulated organisms may be helpful in identifying individuals with isolated absence or hypoplasia of the spleen. However, the absence of these features does not exclude splenic malfunction, although it may make the diagnosis more difficult.

Physical

• The spleen is not usually palpable during the physical examination, except in individuals with thin abdominal musculature.
• Patients with sickle cell disease, particularly children, may have enlarged nonfunctional spleens (functional asplenia). 
• In visceral heterotaxy, a right-sided liver may be mistaken for splenic enlargement.
• The physical findings depend on the associated anomalies.

Causes

• Asplenia and polysplenia may be sporadic or familial.
• Because congenital asplenia has been documented in multiple members of the same family and because it is a component of several well-defined syndromes, genetic factors may play an important role in its pathogenesis. However, no specific genetic defect has been identified.
• Both asplenia and polysplenia have been described in the same family; this finding suggests that these defects may define a spectrum of related conditions.
• Surgical splenectomy may occur after significant splenic trauma or other clinical disorders, such as idiopathic (autoimmune) thrombocytopenic purpura.

Differential Diagnoses

Other Problems to Be Considered

Immune deficiency
Aberrant (wandering) spleen

Workup

Laboratory Studies

• Often the first clues to functional asplenia in an asymptomatic patient are abnormalities in the peripheral blood smear.
  • The initial evaluation should begin with a review to identify HJ bodies (see Media file 1).
  • The nuclear remnants are small, round, densely stained inclusions in RBCs. They can be seen as a normal variant in the newborn period and are occasionally seen in leukemia, steatorrhea, and a variety of anemias (megaloblastic anemia, dyserythropoietic anemia, thalassemia).
  • The presence of HJ bodies in the peripheral smear of an individual older than 7 days should suggest splenic dysfunction.
  • Other red cell abnormalities include an increased presence of target cells, Heinz bodies, Pappenheimer bodies (small basophilic inclusions that contain nonheme iron), reticulocytes, and spherocytes.
  • In addition, thrombocytosis and leukocytosis are observed because the spleen functions as a reservoir for these blood cells.
• Another helpful means of screening the splenic function is by determining the pit (autophagic vacuoles) count (ie, counting the number of pocked erythrocytes).
  • Normally, less than 2% of red cells have these pocks or pits. A pocked erythrocyte count of more than 3.5% suggests functional hyposplenia, and a count of more than 12% is indicative of asplenia.
  • This technique involves the use of special equipment (Nomarski optics) that is not always readily accessible.
• An assessment of the argyrophilic granules in the peripheral smear may be a helpful and easy method to detect splenic dysfunction, but the procedure needs further evaluation.
• HJ body quantitation by flow cytometry has also been described as a way to assay for splenic function but is not currently available, except in specialized laboratories.

Imaging Studies

• Various imaging modalities may be helpful in defining splenic anomalies.
• Certain associated anomalies, especially cardiac and visceral changes, often lead to further evaluation of the spleen.
• Abdominal ultrasonography can be performed to document the presence of the spleen and its size, and newer ultrasonography techniques with color Doppler ultrasonography have shown promise in assessing splenic function. A small spleen with absent parenchymal vascularization on color Doppler ultrasonography has been associated with functional asplenia, but this should be confirmed with further imaging before declaring a patient functionally asplenic.
• The absence of the spleen is best confirmed with a technetium-99m radionuclide scan. This agent is taken up by the reticuloendothelial cells and enables better assessment of splenic function. Similarly, as a result of functional asplenia, patients with sickle cell disease who still have normal-sized and even enlarged spleens demonstrate absent or decreased splenic uptake of technetium-99m sulfur colloid.
• Absence of the intrahepatic segment of the inferior vena cava should trigger careful evaluation of abdominal masses, which could represent splenules. These masses can be confused with multiple metastatic lesions in patients, especially adults, in whom asplenia or polysplenia is undiagnosed.
• MRI or CT scanning of the abdomen may also reveal absence or hypoplasia of the spleen. These studies have no place in the routine workup of isolated asplenia or hyposplenia but may be useful if they are obtained for other accompanying indications, such as visceral heterotaxy. Newer MRI techniques have expanded the role of MRI in the detection and characterization of splenic diseases.⁵
• Computerized models are available to determine the splenic volume, but this approach is mainly used to judge the increased size (eg, tumors, infiltrations) of organs. With more experience, computerized models may provide important information about conditions that decrease the size and volume of the spleen.
• If the spleen is not visualized with radiographic imaging and if no hematologic data support the diagnosis of asplenia, the extremely rare condition of wandering spleen may be considered. In this condition, a functional spleen is present; however, because of its long pedicle, it may be in an abnormal location, such as the pelvis.

Histologic Findings

• A hypoplastic spleen may exhibit a hyperemic red pulp with underdevelopment of the white pulp and a paucity of lymphoid follicles.
• When hyposplenia is secondary to an underlying hemoglobinopathy such as sickle cell disease, specific histologic features may be observed because of infarction (see History).

Treatment

Medical Care

Once the diagnosis of anatomic or functional asplenia is confirmed, aggressive management is the key to decreasing the morbidity and mortality associated with this condition. Newborn diagnosis of sickle cell disease is essential because the first manifestation of the hemoglobinopathy in these infants may be an asplenia-related fatal bacteremia. Any episode of fever or signs of infection should be promptly and aggressively treated.

Medical care involves 4 key components: antibiotic prophylaxis, appropriate immunization, aggressive management of suspected infection, and parent education.

• Antibiotic prophylaxis
  • Antibiotic prophylaxis should be initiated immediately upon the diagnosis of asplenia because these patients are at significant risk of pneumococcal infections. For children younger than 2 years, oral penicillin V may be given twice a day. Amoxicillin has also been recommended as an appropriate prophylactic antibiotic. Erythromycin is an alternate choice in patients who are allergic to penicillin.
  • In general, antimicrobial prophylaxis should be considered for all children with asplenia or splenic dysfunction until age 5 years and for at least 1 year after surgical splenectomy. Some experts recommend continuing prophylaxis into adulthood, particularly for high-risk patients. 
  • Numerous controversies surround when to discontinue antimicrobial prophylaxis in asplenia and hyposplenia (if it should be discontinued at all). Arguments for cessation of prophylaxis include poor patient compliance and the development of resistant bacterial strains in patients on daily antibiotics. Those in favor of lifelong prophylaxis cite case reports of overwhelming postsplenectomy sepsis that occurs years after removal of the spleen. Currently, most guidelines leave the option open to continue lifelong prophylaxis based on the clinical circumstances of the individual patient.
• Immunization
  • All patients should receive all standard childhood and adolescent immunizations at the recommended age. Most importantly, vaccinations against encapsulated organisms, including pneumococcal conjugate and/or polysaccharide, H influenzae type b conjugate, and meningococcal conjugate and/or polysaccharide vaccines, should be administered on the standard schedule.
  • Approximately 80% of the pediatric pneumococcal bacteremias in the United States are caused by the 7 serotypes covered in the conjugate vaccine: 4, 6B, 9V, 14, 18C, 19F, and 23F. The conjugate vaccine has been effective in dramatically reducing the occurrence of invasive pneumococcal disease. In children younger than 2 years, the incidence of all invasive pneumococcal infections has decreased by 80% after conjugate vaccine was recommended in the routine childhood immunization schedule. Infections caused by vaccine and vaccine-related serotypes have decreased by 90% in older children and adults.
  • The immunization schedule for pneumococcal conjugate vaccine (PCV7) consists of a primary series of 4 doses (0.5 mL each) at age 2, 4, 6, and 12-15 months. Catch-up immunization schedules are published regarding appropriate dosing schedules for children aged 5 years or younger. Administration of a single dose of PCV7 to children of any age is not contraindicated, especially for patients with asplenia or splenic dysfunction who are at high risk for invasive pneumococcal disease.
  • The pneumococcal polysaccharide vaccine against 23 serotypes (PPV23) should be given after age 24 months for supplemental protection. PCV7 should be administered first, with administration of PPV23 at least 8 weeks after the last dose of PCV7. A booster dose 3-5 years after the first dose of PPV23 is appropriate.
  • Patients should also receive quadrivalent meningococcal vaccine. Two licensed meningococcal vaccines are available in the United States against serotypes A, C, Y, and W-135, and another vaccine against serotype C is available in Europe. Meningococcal conjugate vaccine (MCV4) was licensed in 2005 for people aged 11-55 years; in 2007, the indication was expanded to include children aged 2 years or older with increased risk of invasive meningococcal disease. Meningococcal polysaccharide vaccine (MPSV4) is licensed for children aged 2 years and older and confers immunity for approximately 4 years. Because of its ability to induce a T-cell response, MCV4 is expected to confer a longer duration of protection than MPSV4; however, the exact duration of protective immunity from MCV4 is unknown. Immunization with MCV4 should be considered in adolescents 3 years after receiving MPSV4. Revaccination schedules with MCV4 are ongoing.
  • The recommended vaccination schedule for H influenzae type b is a primary series of 3 doses given at age 2, 4, and 6 months or 2 doses given at age 2 and 4 months, depending on the particular conjugate vaccine product administered. A booster dose at age 12 months is recommended for all vaccine products. Children who are undergoing scheduled splenectomy after completion of their primary series and booster dose, may benefit from an additional dose of conjugate vaccine at least 7-10 days before surgery. Catch-up immunization schedules regarding H influenzae type b vaccine are published.
  • Yearly influenza vaccine is also recommended to minimize the likelihood of secondary bacterial infections.
• Management of suspected infection
  • The risk of serious bacterial infection is always present in these patients. Many patients have trivial symptoms yet rapidly develop fulminant sepsis and death within hours.
  • All patients with impaired splenic function with suspected infection must be urgently and promptly evaluated. Obtain blood, urine, and, if indicated, cerebrospinal fluid (CSF) cultures. Initiate broad-spectrum intravenous antibiotics effective against S pneumoniae, H influenzae type b, and N meningitidis. Because of the fulminant nature of infections with these agents, intravenous antibiotics need to be initiated before bacteriological results are available. Second-generation or third-generation cephalosporins may be the initial choices. If multiple-drug resistance is a concern, vancomycin should be added to the regimen. In addition, many patients require supportive care with intravenous fluids, volume expanders, and pressor support.
  • Because of the potential rapid progression of a serious bacterial infection, some experts recommend that asplenic patients have access to "stand-by" antibiotics, which can be initiated at the first sign of infection (fever, chills, or malaise). That the initiation of "stand-by" antibiotics is not a substitute for seeking immediate medical attention at the onset of an illness cannot be overemphasized.
  • Patients with asplenia are at an increased risk of sepsis, shock, and meningitis secondary to Capnocytophaga canimorsus resulting from dog, cat, or rodent bites. The diagnosis may be made by means of Gram staining of the buffy coat, blood, and CSF cultures. Early treatment with penicillin is the therapy of choice, but cephalosporins, clindamycin, and erythromycin may also be used.
• Parent education
  • The most important component in the treatment of these patients is parent education. Risks must be explained to all caretakers because they are an integral part of the management team. Seeking medical advice at the first sign of illness is crucial.
  • Ongoing education must become a part of each physician-parent encounter so that the parents remain vigilant, which allows potentially serious infections to be identified early and managed aggressively. The child should wear a Medic Alert bracelet that reads "Asplenia" or "No Spleen." Written instructions should be given to the parents in a form that they can keep with them. For example, they can be given a wallet-sized card with the child's diagnosis and concise guidelines for early treatment and intervention.

Surgical Care

• Elective splenectomy for conditions such as hemolytic anemia are strongly discouraged before age 6 years and should be delayed as long as possible.
• Options to splenectomy should be considered when appropriate. These include partial splenectomy or embolization, conservative management of splenic trauma, and autotransplantation.
• To the author's knowledge, no data support the routine use of prophylactic antibiotics in the perioperative period.
• When surgical splenectomy is imminent, administration of pneumococcal, H influenzae type b, and meningococcal vaccines at least 2 weeks before splenectomy, if possible, is appropriate. If the immunizations are not received prior to surgery, some recommend immunization 14-21 days postsurgery because of enhanced immune response, compared with immediately postsurgery.
• Surgical splenectomy in patients with immunodeficiency should be avoided because of increased risk of invasive bacterial infections.

Activity

• No restrictions on activities are usually advised.
• Infections with H influenzae type b and pneumococcal and meningococcal bacteria are known to be increased among immunologically competent children and adults in daycare centers, college dormitories, military barracks, and other crowded facilities. Therefore, the risks of these situations should be explained to patients and their families.

Medication

The aim of medical therapy is to prevent invasive disease secondary to polysaccharide-encapsulated organisms, especially pneumococci. Penicillin and amoxicillin are currently the drugs of choice.

Antibiotics, prophylactic

These agents are used to prevent invasive bacterial disease. Antibiotic prophylaxis is given to patients before they undergo procedures that may cause bacteremia.

Penicillin V (V-Cillin K, Veetids)

Bactericidal b -lactam antibacterial antibiotic. Main activity is against gram-positive organisms such as streptococci, some gram-negative organisms, and anaerobes. Approximately 60% of PO dose is absorbed. Best taken on empty stomach. Some prefer amoxicillin because it is more bioavailable and less expensive. Preferred for children <2 y. PO susp (125 or 250 mg/mL) available.

Dosing

Adult

250 mg PO bid

Pediatric

<5 years: 125 mg PO bid
>5 years: Administer as in adults

Interactions

Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, decreasing effectiveness 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; rash commonly observed; anaphylactic shock, erythema nodosum, and interstitial nephritis less common; possible cross-reactivity with cephalosporin allergy

Erythromycin (EES, E-Mycin, Eryc)

Used for those with penicillin hypersensitivity. Limited activity against H influenzae. Bacteriostatic antibiotic that acts mainly by inhibiting protein synthesis. Administer >1-2 h pc. PO susp, chewable tab, and enteric-coated tab available.

Dosing

Adult

250 mg PO bid

Pediatric

Administer as in adults

Interactions

Inhibits CYP3A4 isoenzymes and decreases terfenadine, cisapride, and astemizole clearance, which may result in serious cardiac arrhythmias; may also increase toxicity of theophylline, digoxin, carbamazepine, triazolam, midazolam, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

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

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects common (give doses pc); discontinue if nausea, vomiting, malaise, abdominal colic, or fever occur

Amoxicillin (Amoxil, Trimox)

Superior bioavailability and stability to gastric acid and has broader spectrum of activity than penicillin. Somewhat less active than that of penicillin against Streptococcus pneumococcus. Penicillin-resistant strains also resistant to amoxicillin, but higher doses may be effective. More effective against gram-negative organisms (eg, N meningitidis, H influenzae) than penicillin, thus, may provide better prophylaxis in children <2 y.
Susp (125, 200, 250, or 400 mg/5 mL) and pediatric drops (50 mg/mL) available.

Dosing

Adult

250 mg PO bid

Pediatric

<5 years: 125 mg PO bid
>5 years: Administer as in adults

Interactions

May reduce effectiveness of PO contraceptives; probenecid increases serum concentration

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 cephalosporin allergy; dose adjustments may be necessary in renal failure; carefully evaluate rash to differentiate nonallergic ampicillin rash from hypersensitivity reaction

Vaccines

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

Because of the increased problem of penicillin resistance in S pneumoniae, prevention with PCV7 in children or PPV23 in children and adults is mandatory. Similarly, immunizations with the conjugated H influenzae type b vaccine and the meningococcal conjugated or polysaccharide vaccine are essential.

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. Accounts for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance. First dose recommended at age 2 mo but can be given in patient as young as 6 wk. Preferred sites of IM injection include the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children. Do not inject in gluteal area or areas where a major nerve trunk or blood vessel may be present.
Three 0.5-mL doses for infants aged 7-11 mo (4 wk apart; third dose after first birthday), 2 doses for 12-23 mo (2 mo apart), 1 dose for >24 mo through 9 y. Minor illnesses such as a mild upper respiratory tract infection with or without low-grade fever are generally not contraindications.

Dosing

Adult

Not established

Pediatric

3 doses of 0.5 mL each at >2-mo intervals, followed by a fourth dose of 0.5 mL at age 12-15 mo; recommended dosing interval is 4-8 wk; administer fourth dose 2 mo or longer after third dose

Interactions

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

Contraindications

Documented hypersensitivity; severe or moderate febrile illness; infants or children with 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 a 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 with sickle cell disease, asplenia, HIV infection, chronic illness, or immunocompromise; caution in coagulation disorders

Pneumococcal vaccine (Pneumovax-23, Pnu-Imune 23)

Polyvalent vaccine used for prophylaxis against infection with S pneumoniae. Used in populations with increased risk for pneumococcal pneumonia (eg, >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, those with conditions associated with rapid antibody decline after initial vaccination)

Interactions

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

Contraindications

Documented hypersensitivity to any component; severe or even a moderate febrile illness; age <2 y; thrombocytopenia or any coagulation disorder contraindicating IM injection unless potential benefits clearly 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

May cause arthralgia, fever, urticaria, Guillain-Barré syndrome (rare)

Haemophilus influenzae type b vaccines (HibTITER, ActHIB, PedvaxHIB)

For routine immunization of children against invasive diseases caused by H influenzae type b. Decreases nasopharyngeal colonization. The CDC Advisory Committee on Immunization Practices (ACIP) recommends that all children routinely receive one of the conjugate vaccines licensed for use in infants beginning at age 2 mo.

Dosing

Adult

Not indicated

Pediatric

Regimens vary depending on product; one example for HibTITER follows.
2-6 months: 0.5 mL IM q2mo for 3 doses
7-11 months: If previously unvaccinated, 0.5 mL IM q2mo for 2 doses
12-14 months: If previously unvaccinated, 0.5 mL IM once
Booster dose: All children, 0.5 mL at age 15 mo or at least 2 mo after last dose of series; if aged 15-71 mo and previously unvaccinated, 0.5 mL IM given only once

Interactions

Corticosteroids or cyclosporine 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-effect relationship with observed postvaccination Guillain-Barré syndrome not established

Meningococcal vaccine (Menomune)

Capsular polysaccharide antigens (groups A, C, Y, and W-135) of N meningitidis. Used 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 CDC guidelines. Routine vaccination is recommended for high-risk groups (eg, deficiencies in late complement components [C3, C5-C-9], functional or actual asplenia, laboratory or industrial exposure to N meningitidis aerosols, travelers or residents of hyperendemic areas). The vaccine induces antibody response for serogroup A in individuals as young as 3 mo, but it is poorly immunogenic for serogroup C in recipients who are younger than 18-24 mo.
For information concerning geographic areas in which vaccination is recommended, contact the CDC at (404)-332-4559.

Dosing

Adult

0.5 mL SC

Pediatric

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; avoid during course of acute illness

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

Deficiencies in late complement components (C3, C5-C9); do not administer IV/IM/ID; functional or actual asplenia; persons with laboratory or industrial exposure to N meningitidis aerosols; travelers to and residents of hyperendemic areas such as sub-Saharan Africa

Meningococcal conjugate vaccine (Menactra)

Capsular polysaccharide antigens (groups A, C, Y, and W-135) of N meningitidis individually conjugated to diphtheria toxoid proteins. Used for active immunization in individuals aged 2-55 years for the prevention of invasive meningococcal disease caused by inclusive serogroups. Routine vaccination also recommended for high-risk groups (eg, those with deficiencies in late complement components [C3, C5-C-9], functional or anatomic asplenia, properdin deficiencies, and travelers or residents of hyperendemic areas).

Dosing

Adult

<55 years: 0.5 mL IM once
>55 years: Not established

Pediatric

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

Interactions

Administration of immunoglobulin within 1 mo or concurrent administration with immunosuppressive agents may inhibit full immunologic response; coadministration with whole-cell pertussis or whole-cell typhoid vaccines may increase endotoxin content

Contraindications

Known hypersensitivity to any component of Menactra vaccine including diphtheria toxoid or a life-threatening reaction after previous administration of a vaccine containing similar components; known history of Guillain-Barré syndrome; known hypersensitivity to dry natural rubber latex

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

Risks include hemorrhage, local pain, headache, or fatigue; Guillain-Barré syndrome has been reported in a temporal relationship following administration of Menactra vaccine; an evaluation of postmarketing adverse events suggests a potential for an increased risk of Guillain-Barré syndrome following Menactra vaccination; persons previously diagnosed with Guillain-Barré syndrome should not receive Menactra vaccine; the stopper of the vial contains dry natural rubber latex, which may cause allergic reactions in latex-sensitive individuals

Influenza virus vaccine

Indicated for active immunization to prevent influenza a and b viruses. Induces antibodies following administration specific to virus strains contained in vaccine. Influenza vaccine contents are determined annually by the US Public Health Service. Typically, 3 live, attenuated virus strains are included in the formulation each year, which antigenically represent the influenza strains likely to circulate the next flu season.

Dosing

Adult

0.5 mL IM for 1 dose each year prior to flu season

Pediatric

<6 months: Not established
6-35 months: 0.25 mL IM once; administer second dose 4 wk after first dose for vaccine-naïve children
3-8 years: 0.5 mL IM once; administer second dose 4 wk after first dose for vaccine-naïve children
>8 years: 0.5 mL IM for 1 dose each year prior to flu season
Fluviron: <4 years: Not established
Fluarix: <18 years: Not established

Interactions

Immunosuppressive therapy (eg, high-dose corticosteroids, chemotherapy) may reduce antibody response

Contraindications

Documented hypersensitivity to vaccine contents including thimerosal, eggs, egg products, or chicken protein; history of Guillain-Barré syndrome; history of neurologic symptoms following vaccination

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

Defer vaccination with acute febrile illnesses or neurological findings until symptoms have abated; may cause soreness at injection site, fever, malaise, and myalgia

Follow-up

Further Inpatient Care

• The most difficult and crucial aspect of asplenia is establishing the diagnosis.
  • Although this task is relatively simple in patients with accompanying anomalies, especially complex cyanotic cardiac problems, and in those with a family history of the condition, the patient with isolated asplenia or hyposplenia may not be easily identified.
  • The diagnosis is often made at autopsy.
• Patients require regular monitoring with an established provider.
• All immunizations, including routine childhood vaccinations and additional immunizations, are recommended (see Medical Care).
  • These vaccinations should be administered at the earliest opportunity.
  • Close observation and monitoring is mandatory, especially in the first few years of childhood, to educate the family and to ensure compliance with antibiotic prophylaxis.

Prognosis

• With early diagnosis and aggressive treatment, the long-term prognosis of a child with isolated congenital asplenia is good.
  • The risk of overwhelming sepsis, although it does not end, significantly decreases in individuals older than 5 years.
  • The primary care physician plays an integral role in the identification and long-term treatment of patients with asplenia.
• Congenital asplenia, polysplenia, and hypoplasia may be underdiagnosed. An increased awareness of their existence may be crucial and life saving in immunocompromised individuals with these conditions.

Patient Education

• See Medical Care.

Miscellaneous

Medicolegal Pitfalls

• Unfortunately, isolated asplenia or hyposplenia is often diagnosed at autopsy.
• A high index of suspicion and increased awareness are important for the diagnosis.

Multimedia

Media file 1: Peripheral blood smear shows Howell-Jolly (HJ) bodies in RBCs.

References

1. Fremont RD, Rice TW. Splenosis: a review. South Med J. Jun 2007;100(6):589-93. [Medline].

2. Leahy RT, Philip RK, Gibbons RJ, et al. Asplenia in ATR-X Syndrome: a second report. Am J Med Genet A. 2005;15;139 (1):37-9. [Medline].

3. Casey B, Devoto M, Jones KL, Ballabio A. Mapping a gene for familial situs abnormalities to human chromosome Xq24-q27.1. Nat Genet. Dec 1993;5(4):403-7. [Medline].

4. US Preventive Services Task Force. Screening for sickle cell disease in newborns: recommendation statement. Am Fam Physician. May 1 2008;77(9):1300-2. [Medline].

5. Committee on Infectious Diseases American Academy of Pediatrics. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th Ed. 2006.

6. Elsayes KM, Narra VR, Mukundan G, et al. MR imaging of the spleen: spectrum of abnormalities. Radiographics. 2005;Jul-Aug;25(4):967-82. [Medline]. [Full Text].

7. Garson A, Bricker JT, McNamara DG. The Science and Practice of Pediatric Cardiology. Vol 3. 1990:1288-97.

8. Gill DG, Kara M, Moore L. Archives of diseases in childhood. Vol 66. 1991:1366.

9. Gorg C, Eickhorn M, Zugmaier G. The small spleen: sonographic patterns of functional hyposplenia or asplenia. J Clin Ultrasound. 2003;Mar-Apr;31(3):152-5. [Medline].

10. Harrod VL, Howard TA, Zimmerman SA, Dertinger SD, Ware RE. Quantitative analysis of Howell-Jolly bodies in children with sickle cell disease. Exp Hematol. Feb 2007;35(2):179-83. [Medline].

11. Katcher AL. Familial asplenia, other malformations, and sudden death. Pediatrics. 1980;65(3):633-635. [Medline].

12. Kevy SV, Tefft M, Vawier GF, Rosen FS. Hereditary splenic hypoplasia. Pediatrics. Nov 1968;42(5):752-7. [Medline].

13. Lane PA, O'Connell JL, Lear JL, et al. Functional asplenia in hemoglobin SC disease. Blood. Apr 15 1995;85(8):2238-44. [Medline].

14. Lin XZ, Chang TM, Tsai HM, et al. Liver, spleen and tumor volume measured by personal computer. Hepatogastroenterology. Mar-Apr 1999;46(26):838-42. [Medline].

15. Lindor NM, Smithson WA, Ahumada CA, et al. Asplenia in two father-son pairs. Am J Med Genet. Mar 13 1995;56(1):10-1. [Medline].

16. Long WA. Ivemark syndrome (cardiosplenic or heterotaxy syndrome). In: Fetal and Neonatal Cardiology. 1990:616-19.

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

18. Melles DC, de Marie S. Prevention of infections in hyposplenic and asplenic patients: an update. Neth J Med. Feb 2004;62(2):45-52. [Medline].

19. Moller JH, Neal WA. Congenital cardiac anomalies. In: Fetal, Neonatal, and Infant Cardiac Disease. 1990:767-71.

20. Morgan MS. Prophylaxis should be considered even for trivial animal bites. BMJ. May 10 1997;314(7091):1413. [Medline].

21. Pearson HA. The spleen and disturbances of splenic function. Hematology. 1993;2:1058-9.

22. Price VE, Blanchette VS, Ford-Jones EL. The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am. Sep 2007;21(3):697-710, viii-ix. [Medline].

23. Price VE, Dutta S, Blanchette VS, 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. 2006;May 1;46(5):597-603. [Medline].

24. Rose V, Izukawa T, Moes CA. Syndromes of asplenia and polysplenia. A review of cardiac and non- cardiac malformations in 60 cases with special reference to diagnosis and prognosis. Br Heart J. Aug 1975;37(8):840-52. [Medline].

25. Stiehm ER. Immunodeficiency disorders. In: Immunologic Disorders in Infants and Children. 4th ed. 1996:326-327.

26. Tham KT, Teague MW, Howard CA, Chen SY. A simple splenic reticuloendothelial function test: counting erythrocytes with argyrophilic inclusions. Am J Clin Pathol. May 1996;105(5):548-52. [Medline].

27. Tribioli C, Lufkin T. The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Development. Dec 1999;126(24):5699-711. [Medline].

28. Waldman JD, Rosenthal A, Smith AL, et al. Sepsis and congenital asplenia. J Pediatr. Apr 1977;90(4):555-9. [Medline].

29. Wang JK, Hsieh KH. Immunologic study of the asplenia syndrome. Pediatr Infect Dis J. Nov 1991;10(11):819-22. [Medline].

Keywords

asplenia, hypoplasia, splenic hypoplasia, absent spleen, nonfunctional spleen, autosplenectomy, hyposplenia, splen, Ivemark syndrome, asplenia syndrome, functional asplenia, congenital asplenia, bacterial sepsis, polysplenia, Klebsiella species, Escherichia coli, Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, malaria, babesiosis, endocardial cushion defects, pulmonary atresia, pulmonary stenosis, transposition of the great vessels, total anomalous pulmonary venous return

double-outlet right ventricle, atrioventricular canal defects, splenosis, respiratory distress, Pearson syndrome, pancreatic insufficiency, sideroblastic anemia, Stormorken syndrome, thrombocytopenia, miosis, Smith-Fineman-Myers syndrome, mental retardation, short stature, cryptorchidism, ATR-X syndrome, thalassemia, Fanconi anemia, Hodgkin disease, systemic lupus erythematous, SLE, rheumatoid arthritis, inflammatory bowel disease, graft versus host disease, nephrotic syndrome

Contributor Information and Disclosures

Author

Joseph C Turbyville, MD, Fellow, Department of Allergy and Immunology, Walter Reed Army Medical Center
Joseph C Turbyville, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, and American College of Allergy, Asthma and Immunology
Disclosure: Nothing to disclose.

Coauthor(s)

Cecilia P Mikita, MD, MPH, Associate Program Director, Allergy-Immunology Fellowship, Chief, Clinical Services, Allergy-Immunology Clinic, Walter Reed Army Medical Center
Cecilia P Mikita, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and Clinical Immunology Society
Disclosure: Nothing to disclose.

Mudra Kumar, MD, MBBS, MRCP, Associate Professor, Department of Pediatrics, University of South Florida College of Medicine
Mudra Kumar, MD, MBBS, MRCP is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Ann O'Neill Shigeoka, MD †, Former Clinical Associate Professor, Department of Pediatrics, Division of Immunology-Rheumatology, University of Utah School of Medicine
Ann O'Neill Shigeoka, MD † is a member of the following medical societies: American Federation for Medical Research, Clinical Immunology Society, Pediatric Infectious Diseases Society, and Society for Pediatric Research
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

John Wilson Georgitis, MD, Consulting Staff, Lafayette Allergy Services
John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Thanks to Oswaldo Castro, MD, for his assistance in reviewing this manuscript and providing expertise with regards to management of patients with sickle cell disease and asplenia.

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