Hypersplenism is a disorder that involves splenic hyperactivity and can accompany any type of splenomegaly. It is mostly induced by hematological conditions and portal hypertension.
Presentation
A person affected by hypersplenism may experience symptoms related to the organ's enlargement, such as discomfort and abdominal pain in the region that corresponds to the spleen's location. The distended spleen often exerts pressure on the gastric walls, leading to decreased appetite. Pancytopenia or selective leukopenia, erythropenia and thrombocytopenia will also produce symptoms and signs. Erythropenia will lead to the typical anemic symptoms (fatigue, pallor), leukopenia renders the individual susceptible to various kinds of infections and decreased platelet levels result in coagulation disorders, which can be observed during the clinical examination (bruising, etc). The presence of sharp, intense pain in the left upper abdominal quadrant may be an indicator of a splenic infarction.
Immune System
- Splenomegaly
Splenic tuberculosis should be considered as an unusual cause of massive splenomegaly and hypersplenism. [ncbi.nlm.nih.gov]
Hypersplenism occurs as a result of splenomegaly, in a variety of ways. [symptoma.com]
Topic Resources Hypersplenism is cytopenia caused by splenomegaly. Hypersplenism is a secondary process that can arise from splenomegaly of almost any cause (see table Common Causes of Splenomegaly). [merckmanuals.com]
- Massive Splenomegaly
Splenic tuberculosis should be considered as an unusual cause of massive splenomegaly and hypersplenism. [ncbi.nlm.nih.gov]
Entire Body System
- Anemia
However, the severe anemia and thrombocytopenia persisted, necessitating transfusions of red blood cells (RBC) and platelets three times a week. [ncbi.nlm.nih.gov]
Thalassamias Thalassemia major (mediterranean anemia,Cooly’s Anemia ) • Dominant autosomal inheritance • Deficit in synthesis of peptide chain . [slideshare.net]
Congenital forms of anemias and hemolytic anemias often have splenomegaly as part of the clinical presentation. [nethealthbook.com]
Overactivity of the spleen can occur without enlargement, as is seen in immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia. Similarly, splenomegaly is not always associated with hypersplenism. [unboundmedicine.com]
In aplastic anemia, the spleen is not enlarged and the marrow is fatty. [for-surgeons.com]
- Pain
Massive splenomegaly treated with PSE may require an extended hospital stay to achieve pain control. Such patients may subsequently require transition to enteral opioids and weaning. [ncbi.nlm.nih.gov]
He had experienced occasional abdominal pain and diarrhea since 1998. Computed tomography (CT) of the abdomen at that time demonstrated calcification of the pancreas and he was diagnosed with chronic pancreatitis. [ginmu.naramed-u.ac.jp]
- Gaucher Disease
Neoplasia: acute lymphoblastic leukaemia (ALL), Hodgkin's disease and non-Hodgkin's lymphoma (NHL), acute or chronic myeloblastic leukaemia, neuroblastoma. Inherited diseases: Gaucher's disease and other storage disorders. [patient.info]
infection, bone marrow invasion, or malignant disease. • Testing for the presence of antibodies to Epstein-Barr virus, cytomegalovirus, parvovirus, HIV-1, or reduced acid beta-glucosidase activity in white blood cells in Gaucher disease should be considered [cram.com]
malaria) Storage diseases (Gaucher’s disease, Letterer-Siwe disease, amyloidosis) Chronic hemolytic diseases (spherocytosis, thalassemia, elliptocytosis) Myeloproliferative disorders Purpura, bruising, and diffuse mucous membrane bleeding are unusual [for-surgeons.com]
- Ascites
However, PSE is associated with many complications, including intermittent fever, abdominal pain, nausea, vomiting, post-embolization syndrome, splenic abscess, splenic rupture, pneumonia, refractory ascites, pleural effusion and gastrointestinal bleeding [clinicaltrials.gov]
Partial splenic artery embolization for thrombocytopenia and uncontrolled massive ascites after liver transplantation. Transplant Proc. 2012; 44 :755–756. doi: 10.1016/j.transproceed.2012.01.066. [ PubMed ] [ CrossRef ] [ Google Scholar ] 49. [ncbi.nlm.nih.gov]
View Article : Google Scholar : PubMed/NCBI 48 Kim H, Suh KS, Jeon YM, Park MS, Choi Y, Mori S, Hong G, Lee HW, Yi NJ and Lee KW: Partial splenic artery embolization for thrombocytopenia and uncontrolled massive ascites after liver transplantation. [spandidos-publications.com]
Hematological
- Easy Bruising
Signs and Symptoms Symptoms include easy bruising, easy contracting of bacterial diseases, fever, weakness, heart palpitations, and ulcerations of the mouth, legs and feet. [diagnose-me.com]
Symptoms of hypersplenism include easy bruising, easy contracting of bacterial diseases, fever, weakness, heart palpitations, and ulcerations of the mouth, legs and feet. [medical-dictionary.thefreedictionary.com]
These may include: fever, night sweats, paleness (pallor), generalized weakness, fatigue, easy bruising, and weight loss. [emedicinehealth.com]
Gastrointestinal
- Abdominal Pain
Post-embolization syndrome consisted mainly of fever, nausea and vomiting, and abdominal pain in the two groups. [ncbi.nlm.nih.gov]
Left upper quadrant abdominal pain associated with splenic friction rubs indicates splenic infraction, a common concomitant of marked splenomegaly. 2. [erli-myblog.blogspot.com]
RESULTS: Three of 4 patients had an improvement in their platelet count, and 3 of 3 had major improvement in abdominal pain/discomfort. [aamds.org]
Complications in our patients like prolonged mild grade fever and abdominal pain after partial splenic embolisation were similar to those described by other authors(2). [ijri.org]
- Hematemesis
The index case is a 32-year-old chronic alcoholic male presented with multiple episodes of hematemesis and melena. [ncbi.nlm.nih.gov]
He was emergently admitted to the hospital in February, 1999, after he experienced severe abdominal pain and a small amount of hematemesis. Physical examination revealed palpable spleen 5 cm below left costal margin. [ginmu.naramed-u.ac.jp]
Others have hematemesis due to gastroesophageal varices. Disorders Associated with Secondary Hypersplenism. [for-surgeons.com]
[…] infectious mononucleosis, kala azar, malaria, TB; infiltrations–eg, Gaucher disease, Niemann-Pick disease, connective tissue disease Clinical If isolated, asymptomatic; primary diseases may be accompanied by malaise, abdominal pain, fever, fullness, purpura, hematemesis [medical-dictionary.thefreedictionary.com]
- Nausea
Post-embolization syndrome consisted mainly of fever, nausea and vomiting, and abdominal pain in the two groups. [ncbi.nlm.nih.gov]
However, PSE is associated with many complications, including intermittent fever, abdominal pain, nausea, vomiting, post-embolization syndrome, splenic abscess, splenic rupture, pneumonia, refractory ascites, pleural effusion and gastrointestinal bleeding [clinicaltrials.gov]
Postembolization syndrome of fever, left upper abdominal pain, nausea, and anorexia are extremely common after splenic artery embolization. All patients should be given patient-controlled analgesia (PCA) for pain control. [evtoday.com]
- Vomiting
Post-embolization syndrome consisted mainly of fever, nausea and vomiting, and abdominal pain in the two groups. [ncbi.nlm.nih.gov]
However, PSE is associated with many complications, including intermittent fever, abdominal pain, nausea, vomiting, post-embolization syndrome, splenic abscess, splenic rupture, pneumonia, refractory ascites, pleural effusion and gastrointestinal bleeding [clinicaltrials.gov]
- Diarrhea
He had experienced occasional abdominal pain and diarrhea since 1998. Computed tomography (CT) of the abdomen at that time demonstrated calcification of the pancreas and he was diagnosed with chronic pancreatitis. [ginmu.naramed-u.ac.jp]
Cardiovascular
- Thrombosis
Splenectomy in cases of hypersplenism involves significant risk of serious complications, including infection, hemorrhage, portal systemic thrombosis, and necrosis of the stomach or small bowel. [ncbi.nlm.nih.gov]
The combination of thrombosis, splenomegaly, and thrombocytopenia (TST) is challenging because anticoagulants are indicated but thrombocytopenia may increase the bleeding risk. [aamds.org]
There was no relationship with fundus gastric varices, rebleeding rate, portal vein thrombosis, degree of periportal fibrosis and biochemical data. Keywords : Hepatosplenic shistosomiasis; Splenectomy; Spleen; Risk factor; Portal vein thrombosis. [scielo.br]
- Heart Disease
We want to report the case of a 12-year-old boy with sickle cell anemia, splenomegaly, and sickle cell heart disease who was treated by radiation therapy for his enlarged spleen because of hypersplenism. [pediatrics.aappublications.org]
- Hypotension
Overwhelming postsplenectomy infection (OPSI), also known as postsplenectomy sepsis syndrome, begins as a nonspecific, flulike prodrome that is followed by a rapid evolution to full-blown bacteremic septic shock—accompanied by hypotension, anuria, and [emedicine.medscape.com]
Skin
- Petechiae
Hemorrhagic bullae of the lips (A) and petechiae on the tongue (B) mark the presentation of this child with idiopathic thromboc... Figure 67-8 Petechiae and ecchymoses in a patient with idiopathic thrombocytopenic purpura. [5minuteconsult.com]
Face, Head & Neck
- Epistaxis
Prior to splenectomy the patient continued to have a marked thrombocytopenia which resulted in recurrent bouts of epistaxis; splenectomy together with tuberculostatic therapy was curative for the condition. [ncbi.nlm.nih.gov]
Clinical fetures • Purpuric patches over skin and mucus membrane • Epistaxis • Heamaturia Hemarthrosis • GIT bleeding • Intracranial bleed • Hess test 32. Investigation • Bleeding time increased • Clotting and prothrombin time normal • Platelet [slideshare.net]
Neurologic
- Encephalopathy
No episodes of variceal bleeding, sepsis or encephalopathy occurred. [ncbi.nlm.nih.gov]
PSE has been used to control hepatic encephalopathy in patients with splenomegaly and spontaneous splenorenal shunts. 9 PSE can be especially beneficial if hepatic encephalopathy is not responding to conservative measures and surgical options including [evtoday.com]
Workup
A detailed clinical examination, complete with medical history, will direct suspicion towards hypersplenism. The physical examination may reveal an enlarged spleen, which, if accompanied by decreased levels of blood components in the blood test, strongly suggests hypersplenism. The patient will most of the times report symptoms consistent with cytopenia: weakness and fatigue due to anemia, frequent infections and bleeding disorders. Other significant findings include a splenic friction rub to detect an infarction of the spleen and the presence of bruits, heard over the splenic artery, which suggests congestion-induced splenomegaly. Enlarged lymph nodes can also be observed and may point towards autoimmune causes or a myeloproliferative condition.
Concerning the blood tests, a complete blood count should be performed, in order to measure white blood cells, red blood cells and platelets. Levels are usually decreased but not profoundly and may produce no prominent symptomatology. As for cellular morphology, spherocytosis and reticulocytosis are frequently observed.
Splenomegaly is often moderate or not palpable; should the need arise, an ultrasonographic scan (US) or a computerized tomography scan (CT) be used to diagnose the enlargement, with the US being the first option. A magnetic resonance imaging scan can help to illustrate soft tissue structure and identify a potential splenic vein occlusion or other vascular irregularities.
The underlying cause should also be identified and treated, depending on the characteristics of each case. An occult infection should be eliminated as a first step if there is no indication towards to another possible cause. Infection is also a cause that should be suspected in areas with a known infectious disease prevalence, especially tropical regions. Thorough testing, including a complete blood count, bone marrow biopsy and a blood culture should be obtained for further diagnostic purposes. Liver function tests can be conducted supplementally and the presence of a lymphoma can be investigated with the aid of flow cytometry as well.
Ultrasound
- Enlargement of the Spleen
Infections: There is enlargement of the spleen in acute pyogenic infection. In septicemia, the spleen is enlarged and called septic spleen. While non-pyogenic bacteria are Tuberculosis, Typhoid, Brucellosis, and Sarcoidosis. [labpedia.net]
Overactivity of the spleen can occur without enlargement, as is seen in immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia. Similarly, splenomegaly is not always associated with hypersplenism. [unboundmedicine.com]
Hypersplenism may occur in any condition in which there is enlargement of the spleen ( see splenomegaly). [oxfordreference.com]
Wikipedia: Splenomegaly an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. [memidex.com]
Splenomegaly is enlargement of the spleen Hypersplenism: is increase in the function of the spleen, so macrophages inside the spleen attack both normal and abnormal cells. [erli-myblog.blogspot.com]
Serum
- Leukopenia
A big spleen can cause anaemia, thrombocytopenia and/or leukopenia just by being that massive. There are traditionally four components that make up hypersplenism: Large spleen (obviously!) [medicguide.blogspot.com]
Unfortunately, these patients may become intolerant to this therapy when it is complicated by hypersplenism with leukopenia and/or thrombocytopenia. [ncbi.nlm.nih.gov]
Leukopenia Increased destruction or sequestration of leukocytes causes the leukopenia observed in splenomegaly. Leukopenia is closely related to neutropenia. [emedicine.medscape.com]
This was a circulating substance which produced active lysis of normal white cells and must have contributed to the leukopenia. [bloodjournal.org]
- Neutropenia
Primary causes are idiopathic thrombocytopenic purpura, congenital hemolytic anaemia and primary splenic neutropenia or pancytopenia. [explainmedicine.com]
Some of these—anemia, neutropenia, and thrombocytopenia—are attributed to hypersplenism. This is secondary to portal hypertension, which may also lead to the formation of esophageal varices. [annals.org]
More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. [arizona.pure.elsevier.com]
Splenomegaly with variable Anaemia Neutropenia Thrombocytopenia Clinical evaluation and upper abdominal ultrasound. Diagnosis requires cytopenia and/or Anaemia, compensatory bone marrow hyperplasia and splenomegaly. [rcpa.edu.au]
PRINCIPLES: Hypersplenism can be defined by thrombocytopenia and/or neutropenia resulting from blood cell sequestration in an enlarged spleen. [ncbi.nlm.nih.gov]
- Reticulocytosis
Reticulocytosis is usual. Possibly splenic ablation (splenectomy or radiation therapy) Vaccination and prophylactic antibiotics for splenectomized patients Treatment is directed at the underlying disorder. [merckmanuals.com]
Anemia White cells May be elevated due to an increased in neutrophils Counts may approach 30 X 10 9 /L Platelets Usually normal Red cells Hb and Hct decreased Normocytic, normochromic anemia Reticulocytes increased Increased MCV is due to prominent reticulocytosis [5minuteconsult.com]
[…] infiltrations–eg, Gaucher disease, Niemann-Pick disease, connective tissue disease Clinical If isolated, asymptomatic; primary diseases may be accompanied by malaise, abdominal pain, fever, fullness, purpura, hematemesis, GI bleeding Lab ↓ RBC survival, reticulocytosis [medical-dictionary.thefreedictionary.com]
- Erythropenia
Pancytopenia or selective leukopenia, erythropenia and thrombocytopenia will also produce symptoms and signs. [symptoma.com]
In clinical practice, any deficiencies should be supplemented; for example, transfusion of erythrocytes and platelets should be given for erythropenia and thrombocytopenia, respectively, and transfusion of whole blood should be carried out for leukopenia [spandidos-publications.com]
- Reticulocytes Increased
Immune Hemolytic Anemia White cells May be elevated due to an increased in neutrophils Counts may approach 30 X 10 9 /L Platelets Usually normal Red cells Hb and Hct decreased Normocytic, normochromic anemia Reticulocytes increased Increased MCV is due [5minuteconsult.com]
Treatment
An appropriate treatment plan is drawn after the underlying condition has been diagnosed. The first step is always a therapy plan involving medications, as many conditions causing hypersplenism can be reversed with drugs and the patient can avoid surgery.
The avoidance of surgical intervention is crucial given the importance of the spleen and the multitude of its functions. Except for the destruction of the old and abnormal blood components, the spleen is responsible for the production of antibodies (eg. IgG) against pathogens that the organism has never in the past been exposed to [5] [6]. It is the largest lymphoid organ in the body and cannot be restored once severely damaged or resected.
However, if the underlying cause cannot be adequately managed or treated in a conservative manner, splenectomy may be unavoidable. The same applies to cases of patients exhibiting solely hypersplenism as a symptom and those affected by chronic hypersplenism. Total splenectomy is a surgical procedure that retains, up to this day, considerable infection risks and morbidity [7], and is therefore viewed as the last resort [8]. Complications following total splenectomy include various infections (frequently affecting the respiratory tract) and severe septicemia, which is also referred to as the "post splenectomy sepsis syndrome". The spleen possesses the ability to neutralize encapsulated bacterial strains, such as pneumococci or H. influenzae; patients are extremely vulnerable to such pathogens once the spleen has been excised and immunocompromised people, children and senior citizens are at greater risk. Furthermore, patients who undergo a splenectomy often need daily antibiotic intake for the rest of their lives to avoid septic phenomena and mandatory vaccination against various encapsulated pathogens. Patients should learn to be cautious and follow a vaccination schedule against pneumococcus, H. influenza and other pathogens.
Patients who present with fever or a diagnosed infection should receive empiric antibiotic treatment, which will be adjusted if the examinations reveal a specific pathogen. Ceftriaxone is the drug of choice; if there is a strong possibility of resistance to penicillin and cephalosporins, vancomycin should be introduced instead [9].
An alternative approach to total splenectomy is the partial splenic embolization: a part of the splenic tissue is ablated and rendered inactive. Patients seem to respond well to this type of treatment with a corresponding correction of pancytopenia. The embolization process involves only a part of the spleen and it is therefore not followed by the same complications as a total splenectomy.
Prognosis
Mortality and morbidity rates greatly vary, depending on the underlying condition that has lead to the occurrence of hypersplenism. Coexistent diseases, old age and severe pancytopenia are all poor prognostic factors. Failure to administer proper treatment and recognize the cause of hypersplenism can result in severe complications or even death.
Etiology
Hypersplenism occurs as a result of splenomegaly, in a variety of ways. The conditions that cause splenomegaly and subsequent hypersplenism can be infectious diseases, hyperplastic conditions, congestion, infiltrative diseases and various other causes. As far as infectious diseases are concerned, any type of pathogen can potentially lead to hypersplenism. Bacteria which cause endocarditis and tuberculosis, fungal and parasitic infections (malaria, schistosomiasis) are all possible causes of a hyperactive spleen. A plethora of viruses can also cause hypersplenism, such as the HIV virus, Epstein-Barr virus and others. The condition can also be a result of abdominal circulatory congestion, as is the case in portal hypertension, portal or hepatic vein occlusion, cirrhosis and congestive heart failure. In the category of infiltrative conditions fall Gaucher disease, Niemann-Pick disease, amyloidosis, histiocytosis, Waldenstrom macroglobulinemia and metastatic cancer.
Lastly, hyperplastic splenomegaly and hypersplenism can be caused by thalassemia, myelofibrosis, lymphoma, chronic lymphocytic leukemia and other conditions. In some cases, hypersplenism remains uncategorized with reference to its cause and is deemed idiopathic. It can also arise as a result of vitamin deficiency (B12) and as a part of the clinical picture of thyrotoxicosis [4].
Epidemiology
A comprehensive study of the incidence of hypersplenism or splenomegaly has yet to be conducted. The rate lies between 2-6% according to two studies carried out in the USA. It is , however, generally accepted that individuals living in the African tropical zone and visitors to these regions run frequently exhibit the tropical splenomegaly syndrome, due to malaria infection.
Pathophysiology
The pathophysiological mechanisms leading to a hyperactive spleen depend on the underlying cause. In a healthy individual, macrophages located in the spleen are responsible for identifying deformed or aged blood cellular components, pathogens or any type of foreign body. Patients who suffer from conditions leading to an altered cellular morphology or autoimmune disorders, exhibit decreased numbers of those blood components, precisely because they are destroyed in the spleen, despite being functional. In these cases, hypersplenism occurs due to overload-induced hyperplasia and splenomegaly is a subsequent finding.
On the other hand, splenomegaly itself may lead to hypersplenism, via various other mechanisms. Conditions such as portal hypertension, amyloidosis or myelofibrosis may be responsible for the distention of the spleen; the organ enlargement leads to an increase in the volume of the blood that is filtered by the spleen. Thus, a greater number of blood components are destroyed, compared to a healthy individual.
Prevention
Since hypersplenism is caused by an underlying condition, patients should responsibly manage their conditions in order to avoid complications, one of which is splenic enlargement and hyperactivity.
Summary
The spleen is a unique organ located in the upper left quadrant of the abdomen and its contribution is vital for the physiological function of the human body. It is the largest lymphoid organ of the body and mediates the destruction of old or abnormal red cells, produces immunoglobulin G (IgG) and properdin, filters the blood in order to remove pathogens and foreign bodies and maintains a hemopoietic role, although secondary in an adult [1].
Hypersplenism involves a given hyperactivity of the spleen. It can be accompanied by splenomegaly, which is usually not extremely prominent. It is important to keep in mind that hypersplenism is, as a definition, distinguished from splenomegaly; the first refers to a functional disorder and the latter refers to an augmentation of the organ's dimensions. Even though the conditions occur at the same time, the terms are not used interchangeably.
As a disorder, hypersplenism typically involves a distended spleen (splenomegaly), decreased levels of leukocytes, erythrocytes and platelets, shorter platelet and erythrocyte lifespan, as well as the "maturation arrest phenomenon". The latter features an increased production of bone marrow precursor cells, with a decline in the levels of mature erythrocytes, leukocytes and platelets; this indicates that the cells are destroyed by the spleen prematurely [2]. All cell lines may be increasingly discarded by the spleen in a case of hypersplenism, but the most common abnormality is anemia (partly dilutional) [3] and thrombocytopenia.
Patient Information
The spleen is an organ located in the abdomen, specifically under the left rib cage. It cannot be felt with the fingertips under normal circumstances and has multiple important functions. Firstly, the spleen is responsible for the production of blood cellular components in an embryo, although the function is undertaken by the bone marrow in adults. Secondly, old and abnormally shaped red blood cells and other blood components are destroyed in the spleen, which is thus able to regulate the consistency of the blood and ensure that only normal and functional components are circulating. The spleen is also responsible for filtering the blood from various microorganisms and produces antibodies against such germs.
Various conditions cause the spleen to enlarge; the more it enlarges, the more blood components it destroys and therefore causes low levels of red blood cells, white blood cells and platelets. In other cases, the spleen destroys otherwise functional blood components, only because they are structurally different than the others, eg. due to an autoimmune disorder.
Hypersplenism means precisely this: the spleen functions hyperactively, exaggerating every function, so that abnormally large numbers of red and white blood cells, as well as platelets, are sequestered. It can occur as a result of infection, autoimmune disorders, and various other causes. The spleen also becomes distended in order to better accommodate the overload (splenomegaly).
Patients who are affected by hypersplenism may complain of a feeling of discomfort in the left side of the abdomen, of fullness, weakness or fatigue. They may be more susceptible to infections because of the low levels of white blood cells and bruise easily. Fever may also be present in more acute cases. An enlarged spleen may put extra pressure on the stomach; as a result, patients feel full even after consuming normal or small quantities of food. Pain in the location just below the left rib cage is not uncommon either. A doctor will diagnose hypersplenism based on the medical history and findings such as a spleen that can be palpated and low levels of blood cellular components revealed by blood tests. A US, CT or MRI scan can also help to diagnose the condition.
Doctors always try to treat the underlying condition first, because many cases of hypersplenism regress after the cause has been eliminated or controlled. In some occasions, chronic hypersplenism or the failure to diagnose any underlying condition, accompanied by the persistence of splenic hyperactivity require a total splenectomy to be performed. A total splenectomy is the complete removal of the spleen and is a procedure that is seen as the last resort to correct hypersplenism. People who have had their spleen removed are naturally more susceptible to infection, may need to take daily antibiotics to prevent infection and also require annual vaccination against some pathogens.
References
- Eichner ER. Splenic function: normal, too much and too little. Am J Med. 1979 Feb; 66(2): 311-20.
- Edwards CRW, Bouchier IAD. Splenomegaly. Davidson's Principles and Practice of Medicine, 17th ed. Toronto: Churchill Livingstone; p: 305.
- Baliga RR. Splenomegaly. 250 cases in clinical medicine, 3rd ed. London: W B Saunders; 1997; p: 318-319.
- Weatherall DJ, Ledingham JGG, Warrell DA. Causes of splenomegaly. Oxford Text Book of Medicine, 3rd ed. New York: Oxford University Press. 1996; p: 3587-3590.
- Likit VV. Immunological impairment and susceptibility to infection after splenectomy. JAMA 1987; 236: 1376-1377.
- Spigos DG, Jonasson O, Mozes M, Capek V. Partial splenic embolisation in the treatment of hypersplenism. AJR 1979; 132: 777-782
- Dickerman JD. Splenectomy and sepsis warning. Paediatrics; 1979; 63: 938-941.
- Cooper MJ, Williamson RCN. Splenectomy: Indication, hazards and alternatives. BJS 1984; 71: 173-80.
- V Shaw JH, Print CG. Postsplenectomy sepsis. Br J Surg 1989 Oct; 76(10): 1074-81.