Asplenia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Anum Dilip, M.B.B.S[2]
Overview
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. The spleen consists of three functional inter-related compartments: red pulp, white pulp, marginal zone. 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. 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 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. They also produce antibodies against Streptococcus pneumonia, Neisseria meningitidis, and Haemophilus influenzae type b. 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. 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. 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. 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.
Historical Perspective
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.
Classification
Asplenia may be classified into two groups based on its cause: Congenital: Isolated asplenia, heterotaxy syndrome, and Acquired: Functional asplenia.
Pathophysiology
The spleen consists of three functional inter-related compartments: red pulp, white pulp, marginal zone. 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. 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 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. 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. 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. 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.
Causes
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.
Differentiating Asplenia overview from Other Diseases
The differential diagnosis of asplenia includes hyposplenia.
Epidemiology and Demographics
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.
Risk Factors
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
screening for asplenia is by the detection of Howell-Jolly bodies (ie, erythrocytes with nuclear remnants) in peripheral blood smear.
Natural History, Complications, and Prognosis
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.
Diagnosis
Diagnostic Study of Choice
Spleen scintigraphy is the gold standard test for the diagnosis of Asplenia.
History and Symptoms
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 Examination
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.
Laboratory Findings
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.
Electrocardiogram
An Electrocardiogram may be helpful in the diagnosis of asplenia with complex cardiac anomalies.
X-ray
An X-ray of the chest can be done to assess Cardiomegaly, Pulmonary oligemia, Dextrocardia.
Echocardiography and Ultrasound
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
CT scan may be helpful to define these structures in large patients or if overlying gas-filled bowel obscures the upper abdominal anatomy.
MRI
MR imaging may be helpful to define these structures in large patients or if overlying gas-filled bowel obscures the upper abdominal anatomy.
Other Imaging Findings
Other Diagnostic Studies
Blood and CSF cultures may be helpful in the diagnosis of asplenia.
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
References