Asplenia
| Asplenia | |
| ICD-10 | D73.0, Q89.0 |
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| ICD-9 | 289.59, 759.01 |
| OMIM | 208530 %271400 208540 |
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Asplenia Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Asplenia On the Web |
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American Roentgen Ray Society Images of Asplenia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:
Synonyms and keywords:
Overview
Historical Perspective
- 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 coeliac 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]
Classification
Pathophysiology
Physiology
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.[2] 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.[4] 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.
Pathology
The spleen plays integral roles in the immune system and reticuloendothelial systems. It also modulates the inflammatory and coagulation cascades.[5] 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 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.[2] 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.[6] About 30% of platelets are sequestrated in the splenic tissue, spleen is the main site of storage of circulating platelels. [4]
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.[4]
Causes
Asplenia is caused by either congenital, acquired conditions, or functional.
Common Causes
Acquired
- Acquired asplenia associated after trauma or surgery, is one of the commonest cause of the absence of splenic tissue.[7]
- Functional asplenia include diseases such as sickle cell (SC) disease, hemoglobin SC disease and sickle beta-thalassemia.[8]
- 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.[5]
Less Common Causes
Congenital
- 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.
- 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.[9]
Differentiating Asplenia from other Diseases
Epidemiology and Demographics
Incidence
- The incidence of overwhelming post-splenectomy infection syndrome (OPSI) is 50% higher in splenectomised patients compared to healthy individuals.[10]
Prevalence
- The prevalence of asplenia is vary among different conditions.[11]
- The prevalence of Functional hyposplenism in Sickle cell disease, almost 100% of cases, and overwhelming post-splenectomy infection syndrome(OPSI) occur more frequently.[12]
- 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%.
Age
- Patients younger than 16 years old are considered to be at higher risk of OPSI due to their immature immune system.[12]
Risk Factors
Common Risk Factors
- Common risk factors in the development of asplenia include:
Less Common Risk Factors
- Less common risk factor include:
- mutations in the gene RPSA, is a risk factor for Isolated asplenia.[14]
- Two human genes, connexin 43 and ZIC3, is a risk factor for heterotaxy syndrome.[15]
Screening
screening for asplenia is by the detection of Howell-Jolly bodies (ie, erythrocytes with nuclear remnants) is recommended. [16]
Natural History, Complications and Prognosis
Natural History
- If left untreated, Patients with asplenia or hyposplenia are at risk of life-threatening infection.[4]
- 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.[5]
Complications
Common complications of asplenia include:
- overwhelming post-splenectomy infection (OPSI)[4]
- Infection with encapsulated microorganisms such as Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae, and parasitic infections such as babesiosis, malaria.
- Waterhouse-Friedrichsen syndrome and Purpura fulminans [17]
- Arterial thrombosis: includes coronary artery disease [5]
- Venous thrombosis: includes deep vein thrombosis, pulmonary embolism, splenic and portal vein thrombosis
- Pulmonary hypertension, associated with right ventricular dysfunction.
Diagnosis
Diagnostic study of choice | History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | X-Ray Findings | Echocardiography and Ultrasound | CT-Scan Findings | MRI Findings | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical Therapy | Surgery | Interventions | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Medical Therapy
Emergency Medical Management of suspected sepsis in Asplenic patient
Asplenia can cause sepsis and require immediate management:[18]
- Children with asplenia for every febrile illness, must be seen by a physician immediately.
- Sepsis in individuals with asplenia or hyposplenia is a medical emergency as these patients can die within several hours of fever onset despite appearing well initially.
- Administration of antibiotic therapy should not be delayed and blood culture should be performed unless there is an obvious nonbacterial source.
- Ceftriaxone: 100 mg/kg/dose, (maximum 2 g/dose) should be given in all asplenic patients.
- Administer both ceftriaxone and vancomycin (60 mg/kg/day in divided doses every 6 h) in case of intermediate or high penicillin-resistant pneumococci.
- If the patient is treated in a clinic or office setting, refer immediately to the nearest emergency department.
- Clinical deterioration can be rapid even after antibiotic administratin so changes in antibiotics should be done after culture reports available.
- Vancomycin and ciprofloxacin can be used if the patient has an allergy to penicillin or cephalosporin. Changes in antibiotics should be done after culture reports available.
- According to the Surviving Sepsis Campaign guidelines, to avoid poor outcomes, patients suspected of sepsis should be started on antibiotics within 1 hour and as per standard sepsis guidelines, aggressive intravenous (IV) hydration should also be promptly initiated as a part of supportive care.[19]
- Also, asplenic patients are prone to developing septic shock, they may require vasopressors to maintain their blood pressure and if patients develop respiratory failure, mechanical ventilation may be necessary for certain circumstances.
Surgery
The mainstay of treatment for asplenia is medical therapy and prevention.[20]
Primary prevention
Vaccination
- Vaccination against these encapsulated bacteria is recommended to prevent asplenia patients from severe infection. Up to 87% of asplenic patients were found to have been infected with Streptococcus pneumoniae, one of the most common bacterial pathogen leading to infection in patients with asplenia.
- Vaccinations are also recommended before splenectomy and after the surgical removal. For those with functional asplenia or autosplenectomy, it is also advised to continue aggressive vaccination schedules. It is recommended that patients should be given the pneumococcal conjugate vaccine (PCV-13) 8 weeks in advance, as well as the pneumococcal polysaccharide vaccine (PPSV-23), Haemophilus influenzae type B vaccine (Hib), and the quadrivalent meningococcal conjugate vaccine 14 days before planned surgery for splenectomy.
- Apart from all these vaccines, patients should be encouraged to receive influenza vaccine, annual vaccination against the common strains of influenza.[21]
Antibiotic Prophylaxis
- Only Immunizations do not protect against infections with encapsulated bacteria, antibiotic prophylaxis Should be given.[18]
- For children
- All patients younger than five years of age should receive antibiotic prophylaxis.
- Birth to three months: Escherichia coli, Klebsiella are of concern in this age group.
- Amoxicillin or clavulanate 10 mg/kg/dose PO q12h, with penicillin VK 125 mg per dose PO q12h OR amoxicillin 10 mg/kg/dose q12h, as an alternative if not tolerated.
- more than 3 months to five years
- Penicillin VK 125 mg per dose PO q12h OR amoxicillin 10 mg/kg/dose PO q12h.
- Liquid amoxicillin tastes better and may be better tolerated than liquid penicillin.
- more than 5 years
- Penicillin V 250 mg or 300 mg per dose q12h OR amoxicillin 250 mg per dose q12h.
- For penicillin, 250 mg is a convenient dose for suspension but tablets are only available as 300 mg
- For children
- The infectious risk in asplenic patients is high during their entire life but it is highest during the first 2 years following splenectomy and the risk decreases over time.[22]
- Along with vaccination, antibiotic prophylaxis should be given.
- Long term prophylactic therapy oral antibiotic penicillin V, or erythromycin in case of allergy, is required for at least 2 years after splenectomy to cover the period during which the infectious risk is highest.
Malaria Prophylaxis
- Asplenic and hyposplenic children must be advised of their increased risk of severe malaria and also take malaria prophylaxis as appropriate for their age and the type of malaria found in the area to which they are travelling and they should always seek travel advice.[23]
Secondary prevention
Effective measures for the secondary prevention of asplenia include:
- Patient should carry an alert card or bracelet and an up-to-date vaccination record.[24]
- Adult with asplenia, if unable to seek medical attention within 2 hours, should have access to preprescribed antibiotics which should be taken at fever onset.
- The risk of infection can be significantly reduced by using systematic, long-term approaches to care for asplenic patients.
- Patient and family education program that addresses the risk of infection in these at-risk patients.[6]
Case Studies
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- ↑ 1.0 1.1 William BM, Corazza GR (2007). "Hyposplenism: a comprehensive review. Part I: basic concepts and causes". Hematology. 12 (1): 1–13. doi:10.1080/10245330600938422. PMID 17364987.
- ↑ 2.0 2.1 2.2 2.3 2.4 Di Sabatino A, Carsetti R, Corazza GR (2011). "Post-splenectomy and hyposplenic states". Lancet. 378 (9785): 86–97. doi:10.1016/S0140-6736(10)61493-6. PMID 21474172.
- ↑ Fachet J, Foris G (1975). "Enodotoxin-induced non-specific resistance to Trypanosoma equiperdum in neonatally thymectomized or splenectomized Wistar rats". Keio J Med. 24 (4): 347–53. doi:10.2302/kjm.24.347. PMID 1228266.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Kirkineska L, Perifanis V, Vasiliadis T (2014). "Functional hyposplenism". Hippokratia. 18 (1): 7–11. PMC 4103047. PMID 25125944.
- ↑ 5.0 5.1 5.2 5.3 Long B, Koyfman A, Gottlieb M (2021). "Complications in the adult asplenic patient: A review for the emergency clinician". Am J Emerg Med. 44: 452–457. doi:10.1016/j.ajem.2020.03.049. PMID 32247651 Check
|pmid=value (help). - ↑ 6.0 6.1 Lee GM (2020). "Preventing infections in children and adults with asplenia". Hematology Am Soc Hematol Educ Program. 2020 (1): 328–335. doi:10.1182/hematology.2020000117. PMC 7727556 Check
|pmc=value (help). PMID 33275684 Check|pmid=value (help). - ↑ 7.0 7.1 Erdem SB, Genel F, Erdur B, Ozbek E, Gulez N, Mese T (2015). "Asplenia in children with congenital heart disease as a cause of poor outcome". Cent Eur J Immunol. 40 (2): 266–9. doi:10.5114/ceji.2015.52841. PMC 4637402. PMID 26557043.
- ↑ Thiruppathy K, Privitera A, Jain K, Gupta S (2008). "Congenital asplenia and group B streptococcus sepsis in the adult: case report and review of the literature". FEMS Immunol Med Microbiol. 53 (3): 437–9. doi:10.1111/j.1574-695X.2008.00422.x. PMID 18564289.
- ↑ MYERSON RM, KOELLE WA (1956). "Congenital absence of the spleen in an adult; report of a case associated with recurrent Waterhouse-Friderichsen syndrome". N Engl J Med. 254 (24): 1131–2. doi:10.1056/NEJM195606142542406. PMID 13322226.
- ↑ Hansen K, Singer DB (2001). "Asplenic-hyposplenic overwhelming sepsis: postsplenectomy sepsis revisited". Pediatr Dev Pathol. 4 (2): 105–21. doi:10.1007/s100240010145. PMID 11178626.
- ↑ LIPSON RL, BAYRD ED, WATKINS CH (1959). "The postsplenectomy blood picture". Am J Clin Pathol. 32: 526–32. doi:10.1093/ajcp/32.6.526. PMID 14417436.
- ↑ 12.0 12.1 Holdsworth RJ, Irving AD, Cuschieri A (1991). "Postsplenectomy sepsis and its mortality rate: actual versus perceived risks". Br J Surg. 78 (9): 1031–8. doi:10.1002/bjs.1800780904. PMID 1933181.
- ↑ Browning MG, Bullen N, Nokes T, Tucker K, Coleman M (2017). "The evolving indications for splenectomy". Br J Haematol. 177 (2): 321–324. doi:10.1111/bjh.14060. PMID 27018168.
- ↑ Bolze A (2014). "[Connecting isolated congenital asplenia to the ribosome]". Biol Aujourdhui. 208 (4): 289–98. doi:10.1051/jbio/2015001. PMID 25840456.
- ↑ Ahmed SA, Zengeya S, Kini U, Pollard AJ (2010). "Familial isolated congenital asplenia: case report and literature review". Eur J Pediatr. 169 (3): 315–8. doi:10.1007/s00431-009-1030-0. PMID 19618213.
- ↑ Corazza GR, Ginaldi L, Zoli G, Frisoni M, Lalli G, Gasbarrini G; et al. (1990). "Howell-Jolly body counting as a measure of splenic function. A reassessment". Clin Lab Haematol. 12 (3): 269–75. doi:10.1111/j.1365-2257.1990.tb00037.x. PMID 2125541.
- ↑ Hale AJ, LaSalvia M, Kirby JE, Kimball A, Baden R (2016). "Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult". IDCases. 6: 1–4. doi:10.1016/j.idcr.2016.08.004. PMC 4995527. PMID 27583208.
- ↑ 18.0 18.1 Salvadori MI, Price VE, Canadian Paediatric Society, Infectious Diseases and Immunization Committee (2014). "Preventing and treating infections in children with asplenia or hyposplenia". Paediatr Child Health. 19 (5): 271–8. PMC 4029242. PMID 24855431.
- ↑ Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R; et al. (2017). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016". Intensive Care Med. 43 (3): 304–377. doi:10.1007/s00134-017-4683-6. PMID 28101605.
- ↑ Waghorn DJ (2001). "Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed". J Clin Pathol. 54 (3): 214–8. doi:10.1136/jcp.54.3.214. PMC 1731383. PMID 11253134.
- ↑ Huebner ML, Milota KA (2015). "Asplenia and fever". Proc (Bayl Univ Med Cent). 28 (3): 340–1. doi:10.1080/08998280.2015.11929267. PMC 4462215. PMID 26130882.
- ↑ Quéffélec C, Billet L, Duffau P, Lazaro E, Machelart I, Greib C; et al. (2020). "Prevention of infection in asplenic adult patients by general practitioners in France between 2013 and 2016 : Care for the asplenic patient in general practice". BMC Fam Pract. 21 (1): 163. doi:10.1186/s12875-020-01237-3. PMC 7425533 Check
|pmc=value (help). PMID 32787857 Check|pmid=value (help). - ↑ Committee to Advise on Tropical Medicine and Travel (CATMAT) (2009). "Canadian recommendations for the prevention and treatment of malaria among international travellers--2009". Can Commun Dis Rep. 35 Suppl 1: 1–82. PMID 19750611.
- ↑ O'Neill NE, Baker J, Ward R, Johnson C, Taggart L, Sholzberg M (2020). "The development of a quality improvement project to improve infection prevention and management in patients with asplenia or hyposplenia". BMJ Open Qual. 9 (3). doi:10.1136/bmjoq-2019-000770. PMC 7410002 Check
|pmc=value (help). PMID 32759171 Check|pmid=value (help).