Asplenia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Asplenia can refer to an anatomic absence of the spleen or functional asplenia secondary to a variety of disease states. The spleen plays integral roles in the immune system and reticuloendothelial systems.The absence of a spleen is a well-known risk factor for severe bacterial infections, especially due to encapsulated bacteria.

Hippocrates made the first description of the gross anatomy of the spleen in 421 BC. In 1899, Chauffard described that increased splenic activity is linked to hemolysis, and in 1910, Sutherland and Brughard performed the first therapeutic splenectomy in a patient with hereditary spherocytosis. In 1919, Morris and Bullock provided initial experimental evidence of the protective role of the spleen against infections.

Asplenia may be classified into two groups based on its cause: Congenital: Isolated asplenia, heterotaxy syndrome, and Acquired: Functional asplenia.

Asplenia can refer to an anatomic absence of the spleen or functional asplenia secondary to a variety of disease states. The absence of a spleen is a well-known risk factor for severe bacterial infections, especially due to encapsulated bacteria. The primary physiologic role of spleen is the filtration and processing of senescent blood cells, predominantly red blood cells and immunologically helps protect against encapsulated microorganisms and response to infectious pathogens. The spleen plays integral roles in the immune system and reticuloendothelial systems.

Asplenia is caused by either congenital, acquired conditions, or functional. Common cause include: Acquired asplenia associated after trauma or surgery, is one of the commonest cause of the absence of splenic tissue, Functional asplenia include diseases such as sickle cell (SC) disease, hemoglobin SC disease and sickle beta-thalassemia, Hyposplenia occurs due to medical conditions such as chronic liver disease, human immunodeficiency syndrome (HIV), malignancies, thalassemia, celiac disease, ulcerative colitis, sarcoidosis, amyloidosis, lupus, rheumatoid arthritis. Less Common Causes include: Congenital asplenia may be isolated or usually seen as a clinical syndrome such as ivemark syndrome.

The differential diagnosis of asplenia includes hyposplenia.

The incidence of congenital asplenia is approximately 1/10,000 to 1/40,000 live births per 100,000 individuals worldwide. Heterotaxy syndrome with asplenia and right atrial isomerism occurring approximately in 1 in 10,000-40,000 births. The prevalence of asplenia is vary among different conditions. The prevalence of Isolated congenital asplenia is 0.51 per million births, in alcoholic liver disease, is about 37-100%, celiac disease 33-76% , Whipple’s disease 47% and in bone marrow transplantation 40% , and in other cases the frequency of hyposplenism is relatively low such as in systemic lupus erythematosus around 7%. The mortality remains high, at greater than 60%, in asplenic patients who are at risk for overwhelming infection and when they are complicated by invasive infection. Patients younger than 16 years old are considered to be at higher risk of OPSI due to their immature immune system. Asplenia occurs slightly more often in males than in females.

Common risk factors include: Trauma; atraumatic indication for splenectomy includes: hematological autoimmune disorder, Idiopathic Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA); Surgery includes: unexplained splenomegaly, autoimmune, malignant. Less Common Risk Factors include: mutation in gene RPSA and human genes, connexin 43 and ZIC3.

screening for asplenia is by the detection of Howell-Jolly bodies (ie, erythrocytes with nuclear remnants) in peripheral blood smear.

If left untreated, Patients with asplenia or hyposplenia are at risk of life-threatening infection. Common complications include: overwhelming post-splenectomy infection (OPSI), Infection with encapsulated microorganisms such as Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae, Arterial and Venous thrombosis, Waterhouse-Friedrichsen syndrome. Less common complications include: infections due to Capnocytophaga, Babesia, and malaria. Prognosis of asplenia is poor.

Spleen scintigraphy is the gold standard test for the diagnosis of Asplenia.

Patients with asplenia may have a positive history of Trauma, Surgery, sickle cell disease, chronic liver disease, human immunodeficiency syndrome (HIV), malignancies, thalassemia, celiac disease, ulcerative colitis, sarcoidosis, amyloidosis, lupus, rheumatoid arthritis, mutations in RPSA, connexin 43 and ZIC3. Common Symptoms include: *Chills, Sore throat, Diarrhoea, muscle aches, [[Abdominal pain], Nausea and vomiting, Neck stiffness, Altered mental status. Less Common Symptoms include Cyanosis, Respiratory distress.

physical findings depend on the associated anomalies. Patients with sickle cell disease, especially children may have enlarged spleen. Physical exam features typically include Cyanosis, Cold extremities, Stiff neck, Breathlessness, Pan-systolic murmur, Pre-cordial bulge, Ejection systolic murmur, Right sided apex beat, Abdominal tenderness.

Detection of Howell-Jolly bodies in peripheral blood smear, is diagnostic of asplenia, Pitted erythrocytes in blood smear increases, Presence of target cells in the peripheral blood smear, Thrombocytosis.

An Electrocardiogram may be helpful in the diagnosis of asplenia with complex cardiac anomalies.

An X-ray of the chest can be done to assess Cardiomegaly, Pulmonary oligemia, Dextrocardia.

An Echo may be helpful in the diagnosis of asplenia with complex cardiac anomalies and an ultrasound may be helpful in the diagnosis of asplenia.

CT scan may be helpful to define these structures in large patients or if overlying gas-filled bowel obscures the upper abdominal anatomy.

MR imaging may be helpful to define these structures in large patients or if overlying gas-filled bowel obscures the upper abdominal anatomy.

There are no other imaging findings associated with asplenia.

Blood and CSF cultures may be helpful in the diagnosis of asplenia.

Emergency Medical Management of suspected sepsis in Asplenic patient with antibiotics and immunization.

The mainstay of treatment for asplenia is medical therapy and prevention.

Effective measures for the primary prevention of infection in asplenic patients include immunizations against Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis, antibiotic prophylaxis, and malaria prophylaxis.

Effective measures for the secondary prevention of asplenia include: Patient should carry an alert card or bracelet and an up-to-date vaccination record. The risk of infection can be significantly reduced by using systematic, long-term approaches. Patient and family education program that addresses the risk of infection in these at-risk patients.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Hippocrates made the first description of the gross anatomy of the spleen in 421 BC. In 1899, Chauffard described that increased splenic activity is linked to hemolysis, and in 1910, Sutherland and Brughard performed the first therapeutic splenectomy in a patient with hereditary spherocytosis. In 1919, Morris and Bullock provided initial experimental evidence of the protective role of the spleen against infections.

• In 421 BC, Hippocrates made the first description of the gross anatomy of the spleen.^[1]
• In 360 BC, Plato, described the spleen as been constructed “with a view of keeping the liver bright and pure.
• In 1899, Chauffard described that increased splenic activity is linked to hemolysis, and in 1910, Sutherland and Brughard performed the first therapeutic splenectomy in a patient with hereditary spherocytosis.
• In 1913, Eppinger was the first to introduced the term hyposplenism to describe the post-splenectomy state.
• In 1916, Kaznelson performed therapeutic splenectomy in a patient with idiopathic thrombocytopenic purpura.
• In 1919, Morris and Bullock provided initial experimental evidence of the protective role of the spleen against infections.^[2]
• In 1935, Diggs provide a histological description of the spleen in sickle cell anemia.^[1]
• In 1952, King and Schumacker reported a series of cases of overwhelming post-splenectomy infections (OPSI) caused by encapsulated bacteria.^[2]
• In 1955, Rowley has demonstrated that splenectomized human beings fail to respond with a significant rise in antibody titer when an antigen is given intravenously.^[3]
• In 1955, Dameshek coined the term hyposplenism to describe a patient with celiac disease.^[2]
• In 1969, Pearson et al, from USA, was the first to discover the term functional hypoplasia, a few decades ago when he identified some children suffering from sickle cell disease, who presented with the same clinical course as in splenectomised patients.^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Asplenia may be classified into two groups based on its cause: congenital, acquired functional. Congenital asplenia includes isolated asplenia or heterotaxy syndrome.

Asplenia may be classified into two groups based on its cause:^[1][2]

• Congenital: Isolated asplenia, heterotaxy syndrome.
• Acquired: Functional asplenia.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Asplenia can refer to an anatomic absence of the spleen or functional asplenia secondary to a variety of disease states. The absence of a spleen is a well-known risk factor for severe bacterial infections, especially due to encapsulated bacteria. The primary physiologic role of spleen is the filtration and processing of senescent blood cells, predominantly red blood cells and immunologically helps protect against encapsulated microorganisms and response to infectious pathogens. The spleen plays integral roles in the immune system and reticuloendothelial systems.

The spleen consists of three functional inter-related compartments: red pulp, white pulp, marginal zone. The red pulp is a sponge-like structure filled with blood flowing through sinuses and cords functions as a filter for blood elements.^[1] The white pulp consists primarily of lymphatic tissue creating structures called germinal centers which contain lymphocytes (activated B-lymphocytes among others), macrophages, and dendritic cells. They are situated in direct contact with splenic arterioles, branches of the splenic artery. Another region of the white pulp is that the periarteriolar lymphatic sheath, which consists of nodules containing mostly B lymphocytes. The marginal zone surrounds the white pulp and consists of blood vessels, macrophages, and specialized B cells.^[2] The primary physiologic role of spleen is the filtration and processing of senescent blood cells, predominantly red blood cells and immunologically helps protect against encapsulated microorganisms and response to infectious pathogens. It contains both hematopoietic and lymphopoietic elements, which provides a basis for extramedullary hematopoiesis when necessary.

The spleen plays integral roles in the immune system and reticuloendothelial systems. It also modulates the inflammatory and coagulation cascades.^[3] It is understood that Asplenia is a variety of clinical settings, and it can refer to an anatomic absence of the spleen or functional asplenia secondary to a variety of disease states. The risk of death from septicaemia is 200 times higher in asplenic patients than the individual with a spleen.^[4] The absence of a spleen is a well-known risk factor for severe bacterial infections, especially due to encapsulated bacteria. The spleen contains 2 types of tissues: white pulp and red pulp. The white pulp is rich in T-cell lymphocytes, naïve B-cell lymphocytes, and macrophages. The antigen-presenting cells (APC) can enter the white pulp and activate T cells, which in turn activate naïve B cells and differentiate into plasma cells that generate immunoglobulin M antibodies followed by immunoglobulin G antibodies. B cells can also act as antigen-presenting cells and has a phagocytic function to help opsonize encapsulated bacteria. About half of the total B cells in the blood express the memory marker CD27 and carry somatic mutations, and are therefore thought to be memory B cells. There are two types of memory B cells in human beings: switched memory B cells and IgM memory B cells. Switched memory B cells, which are the final product of germinal center reactions, produce high-affinity antibodies and have a protective function against infection. IgM memory B cells, need the spleen for their survival and generation and have the ability to produce natural antibodies. They also produce antibodies against Streptococcus pneumonia, Neisseria meningitidis, and Haemophilus influenzae type b. They can initiate T-cell-independent immune responses on infection or vaccination with capsular polysaccharide antigens.^[1] The red pulp has macrophages and is responsible for filtering damaged, older red blood cells as well as phagocytosing opsonized bacteria. Due to this role of removing damaged erythrocytes, the spleen also plays an important role in the defense against intraerythrocytic parasitic infections such as malaria and Babesia.^[5] About 30% of platelets are sequestrated in the splenic tissue, spleen is the main site of storage of circulating platelels. ^[2]

Functional asplenia is associated with sickle cell anemia, hemoglobin sickle cell disease, and sickle cell hemoglobin β thalassemia. Patient with these hemoglobinopathies starts losing a splenic function, where the spleen is initially enlarged due to excessive red cell entrapment results in atrophy and degeneration in advanced disease. This atrophy is called autosplenectomy and may be consequent] to multiple acute episodes of entrapment of massive red cell volumes in the splenic tissue, followed by splenic infarctions. Functional hyposplenism associated with celiac disease and inflammatory bowel disease leads to spleen’s reticuloendothelial atrophy due to loss of lymphocytes through the inflamed enteric mucosa. Hyposplenism in autoimmune disorders one of the major mechanisms could be reticuloendothelial block due to circulating [[immune complexes]. In hematologic and neoplastic disorders, it is probably due to splenic tissue infiltration by tumor cells or due to vascular occlusion. Hyposplenism in hepatic disorders, might be caused by disruption of normal hepatic microcirculation due to portal hypertension. In acute or chronic alcohol consumption, direct toxic effect of alcohol is implied in all disorders.^[2]

Genes involved in the pathogenesis of Isolatd congenital asplenia include: Mutations in RPSA exons can affect the translated or untranslated regions and can underlie Isolatd congenital asplenia(ICA) with complete or incomplete penetrance.^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Asplenia is caused by either congenital, acquired conditions, or functional. Common cause include acquired asplenia associated after trauma or surgery, is one of the commonest cause of the absence of splenic tissue, Functional asplenia include diseases such as sickle cell (SC) disease, hemoglobin SC disease and sickle beta-thalassemia, Hyposplenia occurs due to medical conditions such as chronic liver disease, human immunodeficiency syndrome (HIV), malignancies, thalassemia, celiac disease, ulcerative colitis, sarcoidosis, amyloidosis, lupus, rheumatoid arthritis. Less Common Causes include congenital asplenia may be isolated or usually seen as a clinical syndrome such as ivemark syndrome.

Asplenia is caused by either congenital, acquired conditions, or functional.

• Acquired asplenia associated after trauma or surgery, is one of the commonest cause of the absence of splenic tissue.^[1]

• Functional asplenia include diseases such as sickle cell (SC) disease, hemoglobin SC disease and sickle beta-thalassemia.^[2]
• Hyposplenia occurs due to medical conditions such as chronic liver disease, human immunodeficiency syndrome (HIV), malignancies, thalassemia, celiac disease, ulcerative colitis, sarcoidosis, amyloidosis, lupus, rheumatoid arthritis.^[3]

• Congenital asplenia may be isolated or usually seen as a clinical syndrome such as ivemark syndrome. This syndrome is classified under heterotaxy syndrome. It is associated with malformation of the heart, and abnormal arrangements of organs of the chest and abdomen along with asplenia or hypoplasia of the spleen.^[4]
• Isolated asplenia are rare and etiology was genetic, due to mutations in the gene RPSA, which encodes ribosomal protein SA, cause more than half of the cases of isolated congenital asplenia, which was first discovered in 2013.
• In heterotaxy syndrome Two human genes, connexin 43 and ZIC3, have been shown to be involved.
• congenital asplenia a very rare anomaly that has been reported in both infants and adults.
• Infantile cases are almost invariably associated with serious congenital malformations of the cardiovascular, gastrointestinal, and pulmonary systems that are not compatible with long life.
• These include atrioventricular communist, pulmonary stenosis or atresia, anomalies of the aorta and great vessels, complete or partial situs in versus, anomalies of the mesenteric and accessory lobes of the lungs.
• In the adult splenic agenesis is usually an isolated and unexpected finding.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

The differential diagnosis of asplenia includes hyposplenia.

The differential diagnosis of asplenia includes hyposplenia. Hyposplenia shares many of the clinical features as asplenia and may precede further functional decline or autosplenectomy. Hyposplenia may be reversible if the underlying condition is treated which is not in the case of asplenia.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

The incidence of congenital asplenia is approximately 1/10,000 to 1/40,000 live births per 100,000 individuals worldwide. Heterotaxy syndrome with asplenia and right atrial isomerism occurring approximately in 1 in 10,000-40,000 births. The prevalence of asplenia is vary among different conditions. The prevalence of Isolated congenital asplenia is 0.51 per million births, in alcoholic liver disease, is about 37-100%, celiac disease 33-76% , Whipple’s disease 47% and in bone marrow transplantation 40% , and in other cases the frequency of hyposplenism is relatively low such as in systemic lupus erythematosus around 7%. The mortality remains high, at greater than 60%, in asplenic patients who are at risk for overwhelming infection and when they are complicated by invasive infection. Patients younger than 16 years old are considered to be at higher risk of OPSI due to their immature immune system. Asplenia occurs slightly more often in males than in females.

• The incidence of congenital asplenia is approximately 1/10,000 to 1/40,000 live births per 100,000 individuals worldwide.^[1]
• The incidence of overwhelming post-splenectomy infection syndrome (OPSI) is 50% higher in splenectomised patients compared to healthy individuals.^[2]
• Heterotaxy syndrome with asplenia and right atrial isomerism occurring approximately in 1 in 10,000-40,000 births, which is the most frequent one of these syndromes.^[3]

• The prevalence of asplenia is vary among different conditions.^[4]
• The prevalence of Functional hyposplenism in Sickle cell disease, almost 100% of cases, and overwhelming post-splenectomy infection syndrome(OPSI) occur more frequently.^[5]
• The prevalence in alcoholic liver disease, is about 37-100%, celiac disease 33-76% , Whipple’s disease 47% and in bone marrow transplantation 40% , and in other cases the frequency of hyposplenism is relatively low such as in systemic lupus erythematosus around 7%.
• The prevalence of Isolated congenital asplenia is 0.51 per million births, indicated by French nationwide study.^[1]

• Asplenic patients are at risk for overwhelming infection and when they are complicated by invasive infection, the mortality remains high, at greater than 60%.^[6]

• Patients younger than 16 years old are considered to be at higher risk of OPSI due to their immature immune system.^[5]

• Asplenia occurs slightly more often in males than in females.^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Common risk factors include: Trauma; atraumatic indication for splenectomy includes: hematological autoimmune disorder, Idiopathic Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA); Surgery includes: unexplained splenomegaly, autoimmune, malignant. Less Common Risk Factors include: mutation in gene RPSA and human genes, connexin 43 and ZIC3.

• Common risk factors in the development of asplenia include:
  • Trauma ^[1]
  • Atraumatic indication for splenectomy includes:^[2]
    • hematological autoimmune disorder
      • Idiopathic Thrombocytopenic Purpura (ITP)
      • Autoimmune Hemolytic Anemia (AIHA)
  • Surgery
  • Unexplained splenomegaly
  • Autoimmune diseases
  • Malignancy

• Less common risk factor include:
  • Mutations in the gene RPSA, is a risk factor for Isolated asplenia.^[3]
  • Two human genes, connexin 43 and ZIC3, is a risk factor for heterotaxy syndrome.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

Screening for asplenia is by the detection of Howell-Jolly bodies (ie, erythrocytes with nuclear remnants) in peripheral blood smear.^[1]

Screening for asplenia is by the detection of Howell-Jolly bodies (ie, erythrocytes with nuclear remnants) in peripheral blood smear.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalpana Giri, MBBS[2]

If left untreated, patients with asplenia or hyposplenia are at risk of life-threatening infection. Common complications including overwhelming post-splenectomy infection (OPSI), Infection with encapsulated microorganisms such as Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae, arterial and venous thrombosis, Waterhouse-Friedrichsen syndrome. Less common complications include infections due to Capnocytophaga, Babesia, and malaria. Prognosis of asplenia is poor.

• If left untreated, patients with asplenia or hyposplenia are at risk of life-threatening infection.^[1]
• Patients with functional asplenia and hyposplenia who have not undergone a splenectomy can present with a life-threatening infection comparable to an OPSI.
• Overwhelming post-splenectomy infection (OPSI) occurs in 5% of patients and has a mortality rate of 38%–70%.
• Functional asplenia is most common in sickle cell disease and occurs within the first 3-5 years of life.^[2]

Common complications

• Recurrent infections^[1]
• Infection with encapsulated microorganisms such as Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae
• Waterhouse-Friedrichsen syndrome and Purpura fulminans ^[3]
• Arterial thrombosis and coronary artery disease ^[2]
• Venous thrombosis such as deep vein thrombosis, pulmonary embolism, splenic and portal vein thrombosis
• Pulmonary hypertension, associated with right ventricular dysfunction.

Less Common complications

• Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria.^[4]

• Prognosis of asplenia is poor, if asplenic patients are not diagnosed on time, and do not receive proper vaccination. These patients are at high risk of infection leads to sepsis, septic shock, and death.^[1]
• Huebner and colleagues, in One case report provides evidence of the poor prognosis in asplenic patients who present with infection despite receiving standard medical care.^[5]
• In Right isomerism (Ivemark syndrome) Prognosis is Poor, 80 % die within first year.^[6]

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