AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Asplenia is a heterogeneous disease that primarily affects the asymmetric organs, including the heart, liver, intestines, and spleen. The first published description of asplenia appeared in 1826. Primary manifestations of this disease include cyanotic congenital heart disease, asplenia, and intestinal malrotation.

Pathophysiology

The exact cause of asplenia has not been defined, but it appears to be multifactorial, with some familial predisposition. Embryologically, it results from failure of development of right-left asymmetry. All thoracic and abdominal organs can be affected; however, other than the anatomic abnormalities, the function of these organs is affected minimally.

Cardiac manifestations can range from minor to severe and are related to incomplete or impaired rotation of the heart. Common cardiac findings include persistence of a left-sided superior vena cava (SVC), anomalous pulmonary venous return, common atrium, endocardial cushion defects, and double outlet right ventricle. In addition, bilateral right atrial appendages may be present in at least 20% of patients with asplenia, and their presence is diagnostic of this syndrome. Other thoracic findings include bilateral morphologic right bronchi and trilobed lungs.

Abdominal findings can include asplenia, transverse liver, and intestinal malrotation. Biliary tract abnormalities have also been described but are rarely of clinical significance.

Frequency

United States

Asplenia has a prevalence of less than 0.1%, but it may account for as much as 1% of the newborn mortality rate. Case reports of familial predisposition exist, but no clear inheritance pattern or gene has been identified. Anatomic findings have been variable in the families described.

Mortality/Morbidity

Without surgery, the mortality rate of asplenia is 95% in the first year of life. Palliative cardiac surgery improves the survival rate, particularly during infancy, but the 5-year mortality rate remains as high as 50%. Mortality can result from congenital heart disease, intestinal malrotation, or sepsis. In one large retrospective review from Canada, the 1-year mortality rate was 80%.

Race

No predilection based on race has been reported.

Sex

No predilection based on sex has been reported.

Age

Heterotaxy occurs in utero, and the onset of clinical symptoms may be during the neonatal period or later in life, depending on the exact cardiac and visceral lesions.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients usually present with symptoms of congenital heart disease in the newborn period. The most common presenting symptom is cyanosis, but murmurs and signs of congestive heart failure can also be presenting signs. A small percentage of patients present with abdominal symptoms or are identified because of an incidental finding of situs abnormalities (eg, dextrocardia, intestinal malrotation). Typically, patients presenting after the newborn period do not have significant congenital heart disease.

Physical

Cyanosis and/or congestive heart failure are the most common physical findings in patients who present in the newborn period. A transverse liver or dextrocardia is often present. Patients who present after the newborn period have predominantly normal physical examination findings, other than a transverse liver and/or dextrocardia. Patients who present with symptoms of malrotation can present with an acute abdomen caused by volvulus.

Causes

The causes of asplenia are unknown, but they appear to be multifactorial and may include inherited predisposition, teratogenic factors, or infection. No racial, sexual, or socioeconomic predispositions exist. Although familial cases have been reported, no genes or loci have been identified. Reported patterns of inheritance have been diverse. In several families with multiple affected children, parental consanguinity is present, or rarely an autosomal recessive inheritance pattern is observed. In at least one family, an X-linked inheritance pattern was reported, with the disease present in 11 related males over 2 generations. Different forms of heterotaxy, including asplenia and polysplenia, may occur within the same family.

The molecular basis for heterotaxy may relate to defects in genes responsible for laterality, such as the growth factor genes: nodal, activin, and lefty.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Kartagener syndrome

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Useful laboratory studies include a CBC with peripheral smear to assess for Howell-Jolly bodies and evidence of impaired splenic function.
• Arterial blood gases to assess for cyanotic heart disease may also be indicated.

Imaging Studies

• Complete echocardiography is indicated in any patient with suspected asplenia to rule out associated congenital heart disease.
• Routine chest radiography is indicated to determine the cardiac size and location, to assess the bronchial anatomy, and to assess abdominal situs.
• In addition, an upper GI study has been proposed as a routine study in asplenic patients because of the high incidence of intestinal malrotation and the risk of volvulus.

Other Tests

• Liver-spleen scanning is indicated to confirm the presence of functional splenic tissue.
• A 12-lead ECG is helpful in assessing patients with asplenia because an abnormal P wave axis is common, and conduction system abnormalities, including complete heart block, sick sinus syndrome, and supraventricular tachycardia (SVT), may occur, although they are less common than in polysplenia.
• Additional studies of cardiac conduction may be indicated based on the clinical setting and ECG findings; in particular, 24-hour Holter monitoring may be recommended.

Procedures

• Cardiac catheterization
• • Patients presenting with cardiac malformations often require cardiac catheterization on one or more occasions. In the newborn period, cardiac catheterization may be indicated to assess systemic and pulmonary venous connections, if this information cannot be obtained from echocardiography. Access can often be achieved through the femoral vein or the umbilical vein, although umbilical venous cannulation is more difficult in patients with asplenia than in those with most other congenital malformations. Venous access from the umbilicus or femoral vein is usually sufficient to perform both a right- and left-heart catheterization.
  • Later, cardiac catheterization may be indicated to determine individual candidacy for surgical intervention. Indications for catheterization may include assessment of pulmonary vascular resistance before palliation with a cavopulmonary connection. Assess pulmonary venous drainage in patients with unobstructed anomalous pulmonary venous return. In such cases, ruling out mild obstruction to pulmonary venous return, as is often observed on anomalous return to a confluence behind the right atrium or to the proximal SVC, is important. Other indications for cardiac catheterization include assessment of ventricular size and visualization and potential embolization of aortopulmonary collateral vessels. Finally, electrophysiological testing may be indicated based on the clinical rhythm presentation.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Medical therapy is typically directed at the findings of the initial evaluation. Anticongestive medication often is beneficial preoperatively in patients with significant left-to-right shunts. Patients with functional asplenia require long-term antibiotic prophylaxis and the pneumococcal vaccine.

Surgical Care

Surgical care is also directed at the findings of the initial evaluation. Patients with significant cardiac disease may require staged palliation or definitive repair. Patients with biliary atresia may require initial palliative surgery followed by liver transplantation.

Consultations

Patients with heterotaxy should have a comprehensive evaluation by a pediatric cardiologist. Depending on the clinical circumstances, an assessment by a pediatric gastroenterologist, pediatric cardiac surgeon, pediatric cardiac electrophysiologist, and/or pediatric anesthesiologist may be warranted.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Patients with congestive cardiomyopathy with significant left-to-right shunts may benefit from treatment for congestive heart failure. In patients with functional asplenia, pneumococcal vaccine and antibiotics for subacute bacterial endocarditis (SBE) prophylaxis are necessary. Antibiotic prophylaxis is administered to patients before procedures that may cause bacteremia are performed. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.

Drug Category: Diuretic agents

Promote excretion of water and electrolytes by the kidneys. Used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites. May be used as monotherapy or in combination to treat hypertension.

Drug Category: Inotropic agents

Positive inotropes increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure. Some may also increase or decrease the heart rate (eg, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances. Those used predominantly for their inotropic effects include cardiac glycosides and phosphodiesterase inhibitors.

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

ACE inhibitors are beneficial in all stages of congestive heart failure. Pharmacologic effects result in a decrease in systemic vascular resistance, reducing blood pressure, preload, and afterload. Dyspnea and exercise tolerance are improved. Unlike diuretics, studies demonstrate improvement of survival and reduced progression of mild or moderate heart failure to more severe stages. Benefits asymptomatic left ventricular dysfunction.

Drug Category: 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.

Drug Category: Antibiotics, prophylactic

Antibiotic prophylaxis is administered to patients before performing procedures that may cause bacteremia.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prognosis

• Without surgery, the mortality rate of asplenia is 95% in the first year of life. Palliative cardiac surgery improves the survival rate, particularly during infancy, but the 5-year mortality rate remains as high as 50%.
• Antibiotic prophylaxis may be needed in patients with splenic insufficiency.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider gastrointestinal malrotation in patients with cardiac and/or visceral heterotaxy: This may potentially result in delayed diagnosis of gut volvulus.
• Failure to consider splenic insufficiency in patients with heterotaxy: Liver-spleen scanning and red blood cell examination should be performed to identify spleen function.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Atkinson DE, Drant S. Diagnosis of heterotaxy syndrome by fetal echocardiography. Am J Cardiol. Nov 1 1998;82(9):1147-9, A10. [Medline].
• Bartram U, Wirbelauer J, Speer CP. Heterotaxy syndrome -- asplenia and polysplenia as indicators of visceral malposition and complex congenital heart disease. Biol Neonate. 2005;88(4):278-90. [Medline].
• Chen SJ, Li YW, Wang JK, et al. Usefulness of electron beam computed tomography in children with heterotaxy syndrome. Am J Cardiol. Jan 15 1998;81(2):188-94. [Medline].
• Ditchfield MR, Hutson JM. Intestinal rotational abnormalities in polysplenia and asplenia syndromes. Pediatr Radiol. May 1998;28(5):303-6. [Medline].
• Eronen M, Kajantie E, Boldt T. Right atrial isomerism in four siblings. Pediatr Cardiol. 2004;24:141-4. [Medline]. [Full Text].
• Freedom RM, Jaeggi ET, Lim JS, Anderson RH. Hearts with isomerism of the right atrial appendages - one of the worst forms of disease in 2005. Cardiol Young. 2005;15:554-67. [Medline]. [Full Text].
• Hashmi A, Abu-Sulaiman R, McCrindle BW, et al. Management and outcomes of right atrial isomerism: a 26-year experience. J Am Coll Cardiol. Apr 1998;31(5):1120-6. [Medline].
• Hofstaetter C, Plath H, Hansmann M. Prenatal diagnosis of abnormalities of the fetal venous system. Ultrasound Obstet Gynecol. Mar 2000;15(3):231-41. [Medline].
• Kawahira Y, Kishimoto H, Kawata H, et al. Morphologic analysis of common atrioventricular valves in patients with right atrial isomerism. Pediatr Cardiol. Mar-Apr 1997;18(2):107-11. [Medline].
• Levine JC, Walsh EP, Saul JP. Radiofrequency ablation of accessory pathways associated with congenital heart disease including heterotaxy syndrome. Am J Cardiol. 1993;72:689-93. [Medline].
• Mahle WT, Silverman NH, Marx GR, Anderson RH. Echo-morphological correlates concerning the functionally univentricular heart in the setting of isomeric atrial appendages. Cardiol Young. 2006;16 Suppl 1:35-42. [Medline]. [Full Text].
• Ruscazio M, Van Praagh S, Marrass AR, et al. Interrupted inferior vena cava in asplenia syndrome and a review of the hereditary patterns of visceral situs abnormalities. Am J Cardiol. Jan 1 1998;81(1):111-6. [Medline].
• Ticho BS, Van Praagh R. Inherited structural heart diseases associated with arrhythmias: Defects in laterality. In: Berul CI, Towbin JA, eds. Molecular Genetics of Cardiac Electrophysiology. Boston, Mass:. Kluwer Academic Publishers;2000:317-328.
• Uemura H, Ho SY, Devine WA, Anderson RH. Analysis of visceral heterotaxy according to splenic status, appendage morphology, or both. Am J Cardiol. Oct 15 1995;76(11):846-9. [Medline].
• Uemura H, Ho SY, Anderson RH, Yagihara T. Ventricular morphology and coronary arterial anatomy in hearts with isometric atrial appendages. Ann Thorac Surg. May 1999;67(5):1403-11. [Medline].
• Wu MH, Wang JK, Lin JL, et al. Supraventricular tachycardia in patients with right atrial isomerism. J Am Coll Cardiol. Sep 1998;32(3):773-9. [Medline].
• Yoo SJ, Kim YM, Choe YH. Magnetic resonance imaging of complex congenital heart disease. Int J Card Imaging. Apr 1999;15(2):151-60. [Medline].
• Zissin R, Rathaus V, Oscadchy A, et al. Intestinal malrotation as an incidental finding on CT in adults. Abdom Imaging. Nov-Dec 1999;24(6):550-5. [Medline].

Article Last Updated: Apr 17, 2006