Asplenia

The spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen plays a crucial role in immune function, blood filtration, and platelet storage. Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. Howell-Jolly bodies are commonly seen on peripheral blood smear. Abdominal imaging and scintigraphy are used for diagnosis. High risk of sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock caused by encapsulated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview requires adherence to a strict vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination schedule and early antibiotic treatment when an infection is suspected. Thromboembolic events are common.

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Overview

Definition

The spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen is one of the secondary lymphatic organs Secondary lymphatic organs The secondary lymphoid organs, also called peripheral lymphoid/lymphatic organs, include MALT, the lymph nodes, and the spleen. These collections of lymphoid tissues provide constant surveillance for pathogens. In their distinct sites, these tissues are filled with immune cells ready to mount a response when antigens are detected. Secondary Lymphatic Organs central to immune function that plays a role in filtering the blood and removing old or damaged erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes. Asplenia is defined as the lack of a spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen or splenic function.

Etiology

  • Congenital:
    • Component of heterotaxy syndrome involving organs of the chest and abdomen
    • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inheritance
  • Functional:
    • Atrophy
    • Infarction
    • Engorgement
    • Infiltration
  • Acquired: 
    • Surgical removal: most common cause 
    • Splenic rupture Splenic rupture Splenic rupture is a medical emergency that carries a significant risk of hypovolemic shock and death. Injury to the spleen accounts for nearly half of all injuries to intra-abdominal organs. The most common reason for a rupture of the spleen is blunt abdominal trauma, specifically, motor vehicle accidents. Rupture of the Spleen

Epidemiology

Epidemiology differs based on etiology.

  • Congenital:
    • Rare
    • Syndromic asplenia is predominant in men.
    • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease, Whipple procedure, and alcoholic liver disease Alcoholic Liver Disease Alcoholic liver disease is a spectrum of disorders ranging from fatty liver to cirrhosis secondary to chronic alcohol abuse. Excessive and prolonged consumption of alcohol results in impairment of the lipolysis pathway, causing inflammatory changes within the hepatocytes. Patients typically present during the hepatitis stage with jaundice, fever, and abdominal pain. Alcoholic Liver Disease are strongly associated with partial splenic disfunction.
  • Functional asplenia: Nearly all patients with sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease (and other hemoglobinopathies) will suffer from functional asplenia.
  • Acquired: The incidence of surgical splenectomy is decreasing because of new surgical techniques.

Pathophysiology

  • Functional asplenia typically begins with hyposplenism:
    • Entrapment of RBCs 
    • Infarction
    • Hyposplenism
    • Autosplenectomy
  • Lack of a filtration function for bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview: increased risk of sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock due to encapsulated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae
    • Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria meningitidis
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella
  • Increased risk of vascular events:
    • Secondary to thrombocytosis
    • Increased circulation of damaged erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes
Table: Causes of asplenia by category
Category Disease/condition
Congenital
  • Heterotaxy syndrome
  • Ivemark syndrome
Iatrogenic
  • Splenectomy (post trauma)
  • Irradiation
Circulatory
  • Splenic artery/vein thrombosis
  • Celiac artery thrombosis
Hematologic/oncologic
  • Sickle cell disease
  • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis
  • Myeloproliferative disorders
  • Graft vs. host disease
  • Malignancy (leukemia, lymphoma, metastases)
Hepatic
  • Alcoholic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease/ cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
  • Chronic hepatitis
  • Portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension
Autoimmune
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
  • Thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
  • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis
GI
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Inflammatory bowel disease
  • Whipple’s disease
Infectious
  • AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
  • Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria
  • Bacterial infections by Pneumococcus, Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae, Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria
Stage iv splenic injury

Stage IV splenic injury in a 34-year-old patient

Image: “Stage IV Splenic injury in a 34 Year Old Patient” by Eskandarlou, M., Derakhshanfar, A. License: CC BY 3.0

Diagnosis

  • History and physical:
    • History of a predisposing syndrome, condition, or trauma
    • Surgical history
  • Laboratory testing:
    • Peripheral blood smear:
      • Howell-Jolly bodies pathognomonic
      • Heinz bodies, target cells, pitted erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes common
    • CBC:
      • Neutrophilia
      • Thrombocytosis
  • Diagnostic imaging:
    • Plain radiography:
      • Reveals abnormal orientation of organs in heterotaxy syndromes
      • May be helpful in trauma
    • MRI
    • Ultrasound
    • Scintigraphy

Management

Management depends on the underlying cause, degree of asplenia, and age. Patients > 5 years of age have a better prognosis. Prevention of infection is the cornerstone of long-term care because of the increased risk of rapidly progressing septicemia that is fatal in 50% of patients.

Infection control

  • Routine vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination:
    • Pneumococcal 
    • Meningococcal
    • H. influenzae (type B)
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza
  • Antibiotic prophylaxis:
    • For 1–2 years after splenectomy
    • Up to 5 years of age
    • Surgical procedures that may predispose to infection by encapsulated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Lifetime, if history of post-splenectomy sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
  • Empiric antibiotic treatment: indicated early when a patient presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever or other signs of infection

Overwhelming post-splenectomy infection (OPSI)

Rapid-onset septicemia:

  • Infection without definitive source accompanied by DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
  • Mortality rate: 50%–70%
Management of fever in an asplenic patient

Management of an episode of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever in an asplenic patient

Image by Lecturio. License: CC BY-NC-SA 4.0

Clinical Relevance

  • Blunt abdominal trauma and penetrating abdominal injury Penetrating abdominal injury Penetrating abdominal injuries are created by an object puncturing the abdominal wall. Injuries can be high velocity, like gunshot wounds, or low velocity, like stab wounds. Different structures can be injured, including the duodenum, spleen, liver, kidneys, and pelvic organs. Penetrating Abdominal Injury: Abdominal injuries are classified as blunt or penetrating, according to the mechanism of injury. Different structures including the duodenum, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, and pelvic organs can be injured. In severe splenic injury, a splenectomy may have to be performed to remove the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen.
  • Mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as "the kissing disease," is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis: also known as “kissing disease,” or infectious mononucleosis. Mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as "the kissing disease," is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis is a highly contagious viral infection caused by the EBV. The common name for mononucleosis stems from its main method of transmission: the spread of infected saliva via kissing. During acute EBV infections, the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen can become enlarged and rupture either spontaneously (rare) or owing to its increased vulnerability to trauma.
  • Spleen: a coffee-bean-shaped organ located in the left posterior upper abdomen (left hypochondriac region) and weighing about 150 grams. The spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen is composed of very soft tissue that is filled with blood, which trickles through the parenchyma and filters out any old or abnormal RBCs and WBCs. The spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen also plays a role in immune function by removing pathogens and producing antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins. Owing to its fragile nature and high vascularization, the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen can rupture easily during abdominal trauma, particularly when it is enlarged.
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly: massive enlargement of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen, rendering it palpable under the left costal arch. Ultrasounds show a bulging shape and rounding of the normally pointed ends. Any ectopic tissue, such as accessory spleens, will also be hypertrophied. Enlargement of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen may occur for different reasons, including infection, internal hemorrhage, or sequestration of abnormal blood cells. Enlargement of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen puts it at risk for rupture during trauma.

References

  1. Pulvirenti, F., et al. (2020). Chapter 48. In Sullivan, K., and Stiehm, R. (Ed.), Stiehm’s Immune Deficiencies Inborn Errors of Metabolism. 2nd ed. pp. 1012–1033. Retrieved April 12, 2021, from https://www.sciencedirect.com/topics/immunology-and-microbiology/asplenia
  2. Quinti, I., Paganelli, R. (2014). Chapter 45. In Sullivan, K., and Stiehm, R. (Ed.), Stiehm’s Immune Deficiencies Inborn Errors of Metabolism. 1st ed. pp. 835–844. Retrieved April 12, 2021, from https://doi.org/10.1016/B978-0-12-405546-9.00045-5
  3. Litz, C.E. The post splenectomy blood picture. Retrieved April 16, 2021, from https://propath.com/the-post-splenectomy-blood-picture/
  4. Chen, M.J., Huang, M.J., et al. (2005). Ultrasonography of splenic abnormalities. World Journal of Gastroenterology. 11(26), 4061–4066. Retrieved April 16, 2021, from http://dx.doi.org/10.3748/wjg.v11.i26.4061
  5. Rubin, L., Schaffner, W. (2014). Care of the asplenic patient. New England Journal of Medicine. 371, 349–356. Retrieved April 16, 2021, from https://doi.org/10.1056/NEJMcp1314291

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