To better describe and understand operative indications in surgery
of the spleen, one could categorize the indications for splenectomy
or procedures of the spleen into eight general areas:
(1) Hypersplenism is characterized by diffuse enlargement of
the spleen by neoplastic disorders, hematopoietic disorders of the
bone marrow, and metabolic or storage disorders. These various disease
processes result in diffuse enlargement of the spleen and amplify the
normal function of elimination of circulating blood cells resulting
in general pancytopenia. Erythrocytes and platelets are most commonly
affected. Hypersplenism also may cause symptoms of early satiety
due to the splenic size.
(2) Autoimmune/erythrocyte disorders. Specific cytopenias
are related either to antibodies targeting platelets, erythrocytes,
or neutrophils. A second category of diseases relates to intrinsic
structural changes within the erythrocyte that lead to a shortened
red blood cell half-life with accelerated splenic clearance. There
is nothing intrinsically wrong with the spleen, and splenic size
is typically normal.
(3) Trauma or injury to the spleen.
(4) Vascular diseases. Splenic vein thrombosis and splenic artery
aneurysm may require splenectomy for treatment.
(5) Cysts, abscesses, and primary splenic tumors are mass lesions
of the spleen. This category includes treatment of simple cysts,
echinococcal cysts, splenic abscess, and various benign neoplasms,
including hamartomas, hemangiomas, lymphangiomas, and rare malignant
(6) Diagnostic procedures. This category of splenectomy occurs
when the spleen is removed primarily to make a clinical diagnosis
when none is available. A subcategory is staging laparotomy for Hodgkin
disease, which has all but been eliminated based on alternative
imaging techniques and current treatment regimens.
(7) Iatrogenic splenectomy. Splenectomy that is performed due
to an incidental injury to the spleen during surgery within the
general abdominal cavity or, specifically, the left upper quadrant,
can be categorized as iatrogenic splenectomy. This category is likely
underreported and may be considered a subcategory of trauma.
(8) Incidental splenectomy. The spleen may be removed as part
of a standard operation to remove the distal pancreas most commonly,
and also for gastric cancers, left-sided renal cell carcinomas,
adrenal cancers, and retroperitoneal sarcomas in the left upper
quadrant. The spleen is removed in these instances because of direct
tumor extension, vascular involvement, or the need for excision
of splenic hilum lymph nodes.
With the increase in splenic preservation for trauma, many institutional
series list medical conditions as the most frequent indications
for splenectomy. Most recent series report 40–50% for
hematologic conditions, 35–40% for trauma, and
20–30% for neoplastic disease. Within the category,
idiopathic thrombocytopenia purpura has the highest incidence for splenectomy.
Each category of disease, including the etiology and pathophysiology
of the disorder, specific indications for splenectomy, alternative
treatments, and the results of splenectomy, is discussed in this
Harbrecht BG et al: Is splenectomy after trauma
an endangered species? Am Surg 2008;74:410.
Morgenstern L et al: Love in the time of spleen: a personal
memoir. J Am Coll Surg 2006;202:335.
Wood L et al: Splenectomy in haematology—a 5-year single
centre experience 2005;10:505.
In the past, the term hypersplenism or increased splenic function
has been used to denote the syndrome characterized by splenic enlargement,
deficiency of one or more blood cell lines, normal or hyperplastic
cellularity of deficient cell lines in the marrow, and increased
turnover of affected cells. Increased understanding of the pathophysiology
of specific disorders has shown that hypersplenism is not synonymous
with splenomegaly. Some disorders in which there is spleen-dependent
destruction of blood elements do not manifest all features of hypersplenism.
For example, splenomegaly is rarely a feature of immune thrombocytopenic
purpura, and splenectomy is not always curative. Conversely, other conditions
that enlarge the spleen may not result in destruction or sequestration of
blood elements with resultant cytopenias. In disorders with known
pathogenesis, the recent trend has been to classify them as separate
disease entities rather than as hypersplenic conditions.
The defects in hypersplenism are exaggerations of normal splenic
functions primarily associated with the red pulp. The principal
cause of cytopenias in hypersplenism is increased sequestration
and destruction of blood cells in the spleen, which is hypertrophied
or increased in volume in a variety of diseases. Etiologic factors
include (1) neoplastic infiltration, (2) disease of the bone marrow
in which the spleen becomes a site of extramedullary hematopoiesis,
and (3) metabolic/genetic disorders such as Gaucher disease.
The hyperplastic spleen is not selective in its hyperfunction in
most of these disorders. The splenomegaly can lead to an increased
turnover in erythrocytes and platelets, with a lesser effect on
leukocytes. For example, about 60% of patients with cirrhosis
develop splenomegaly and 15% develop hypersplenism. The
hypersplenism of cirrhosis is seldom of clinical significance; the anemia
and thrombocytopenia are usually mild and rarely are indications
The clinical findings depend largely on the underlying disorder
or are secondary to the depletion of circulating blood elements
caused by the hypersplenism (Table 27–1).
Manifestations of hypersplenism usually develop gradually, and the
diagnosis often follows a routine physical or laboratory examination.
Some patients experience left upper quadrant fullness, discomfort
(can be severe), or early satiety. Others have hematemesis due to gastroesophageal
Table 27–1. Disorders Associated with Secondary Hypersplenism. |Favorite Table|Download (.pdf)
Table 27–1. Disorders Associated with Secondary Hypersplenism.
|Congestive splenomegaly (cirrhosis, portal or splenic vein obstruction)|
|Neoplasm (leukemia, metastatic carcinoma)|
|Inflammatory disease (sarcoid, lupus erythematosus, Felty
|Acute infections with splenomegaly|
|Chronic infection (tuberculosis, brucellosis, malaria)|
|Storage diseases (Gaucher disease, Letterer-Siwe disease,
|Chronic hemolytic diseases (spherocytosis, thalassemia, glucose-6-phosphate
dehydrogenase deficiency, elliptocytosis)|
|Myeloproliferative disorders (myelofibrosis with myeloid
Purpura, bruising, and diffuse mucous membrane bleeding are unusual
symptoms despite the presence of thrombocytopenia. Anemia may produce
significant fatigue that may be the chief complaint in this patient
population. Recurrent infections may be seen in patients with severe leukopenia.
Patients with primary hypersplenism usually exhibit pancytopenia
of moderate degree and generalized marrow hyperplasia. Anemia is
most prominent, reflecting the destruction of erythrocytes in the
hypertrophied red pulp of the spleen. Thrombocytopenia occurs because
of sequestration of platelets but also possibly because of increased turnover. In most cases,
more immature cell types such as reticulocytes are present, reflecting
the overactivity of the bone marrow to compensate for the pancytopenias.
One exception is myeloid metaplasia, in which dysfunction of the bone
marrow is the primary defect.
of Splenic Size
Before it becomes palpable, an enlarged spleen may cause dullness
to percussion above the left costal margin. Splenomegaly is manifested
on supine x-rays of the abdomen by medial displacement of the stomach
and downward displacement of the transverse colon and splenic flexure.
CT scan is useful for differentiating the spleen from other abdominal masses
and for demonstrating splenic enlargement or intrasplenic lesions. Some
of the largest massive spleens (spleen weight > 1500 g) occur in
these types of disease. Finding the edge of the spleen below the
iliac crest and across the abdominal midline is frequent.
Leukemia and lymphoma are diagnosed by marrow aspiration, lymph
node biopsy, and examination of the peripheral blood (white count
and differential). In hereditary spherocytosis, there are spherocytes,
osmotic fragility is increased, and platelets and white cells are
normal. The hemoglobinopathies with splenomegaly are differentiated
on the basis of hemoglobin electrophoresis or the demonstration
of an unstable hemoglobin level. Thalassemia major becomes apparent
in early childhood, and the blood smear morphology is characteristic.
In myelofibrosis, the bone marrow shows proliferation of fibroblasts
and replacement of normal elements. In idiopathic thrombocytopenic
purpura, the spleen is normal or only slightly enlarged. In aplastic
anemia, the spleen is not enlarged and the marrow is fatty.
The course, response to treatment, and prognosis of the hypersplenic
syndromes differ widely depending on the underlying disease and
its response to treatment; these are discussed for each particular disorder.
The indications for splenectomy are given in Table
Table 27–2. Indications for Splenectomy. |Favorite Table|Download (.pdf)
Table 27–2. Indications for Splenectomy.
|Splenectomy always indicated|
|Primary splenic tumor (rare)|
|Hereditary spherocytosis (congenital hemolytic anemia)|
|Splenectomy usually indicated|
|Chronic immune thrombocytopenic purpura|
|Splenic vein thrombosis causing gastric varices|
|Splenic abscess (rare)|
|Splenectomy sometimes indicated|
|Autoimmune hemolytic disease|
|Elliptocytosis with hemolysis|
|Nonspherocytic congenital hemolytic anemias|
|Hodgkin disease (for staging)|
|Thrombotic thrombocytopenic purpura|
|Splenic artery aneurysm|
|Splenectomy rarely indicated|
|Sickle cell anemia|
|Congestive splenomegaly and hypersplenism due to portal hypertension|
|Hairy cell leukemia|
|Splenectomy not indicated|
|Splenomegaly with infection|
|Splenomegaly associated with elevated IgM|
|Hereditary hemolytic anemia of moderate degree|
Splenectomy may decrease transfusion requirements, decrease the
incidence and number of infections, prevent hemorrhage, and reduce
pain. The course of congestive splenomegaly due to portal hypertension
depends on the degree of venous obstruction and liver damage. The
hypersplenism is rarely a major problem and is almost always overshadowed
by variceal bleeding or liver dysfunction.
Neoplastic diseases in which splenectomy may play a role in management
of hypersplenism include chronic lymphocytic leukemia (CLL), hairy
cell leukemia, and non-Hodgkin lymphoma. Lymphoma is discussed in
detail in Chapter 44. Related neoplastic disorders
of idiopathic myelofibrosis and mastocytosis are also discussed
as precursors or variants of neoplastic diseases in which splenectomy
are occasionally indicated.
CLL is a low-grade neoplasm of B cell lineage characterized by
accumulations of populations of lymphocytes that are mature morphologically
but functionally incompetent. In the United States, CLL occurs as
25–30% of all leukemias with mean age at diagnosis
of 72. The clinical manifestations and natural history are variable,
but initially the disease tends to be indolent. In more advanced
stages, splenomegaly, which is frequently massive, is a common characteristic
of CLL. Most symptoms related to the spleen are from thrombocytopenia
and anemia due to secondary hypersplenism (80–90% of splenic
symptoms). Ten to 20 percent of patients may have symptoms primarily related
to pressure from the size of the enlarged spleen.
Other causes of cytopenia in CLL relate to decreased cellular
production from the bone marrow. Bone marrow failure can be due
to replacement with leukemic cells or to depletion of the bone marrow as
a toxic effect of prior antitumor chemotherapy.
Splenectomy in patients with CLL corrects thrombocytopenia in
70–85% of cases, neutropenia in 60–70%,
and anemia in 50–60% of cases. The median duration
of benefit for both platelets and red cell populations is well over
1 year. Patients with smaller spleens preoperatively, lower preoperative
platelet counts, and extensive prior chemotherapy are less likely
to respond to splenectomy. However, a positive bone marrow aspirate
for leukemic cells is not a contraindication to splenectomy in CLL.
Patients who do not have a good performance status should not undergo
splenectomy, since patients in terminal stages have unacceptable
Hill J et al: Laparoscopic splenectomy for autoimmune
hemolytic anemia in patients with chronic lymphocytic leukemia:
a case series and review of the literature. Am J Hematol 2004;75:134.
Petroianu A et al: Subtotal splenectomy for the treatment of
chronic lymphocytic leukemia. Ann Hematol 2003;82:708.
Ruchlemer R et al: Splenectomy in mantle cell lymphoma with
leukemia: a comparison with chronic lymphocytic leukemia. Br J Haematol
Subbiah V et al: Outcomes of splenectomy in T-cell large granular
lymphocyte leukemia with splenomegaly and cytopenia. Exp Hematol
Hairy cell leukemia is a low-grade lymphoproliferative disorder
with characteristic “hairy cells” (ie, B lymphocytes
with irregular cytoplasmic protrusions positive for tartrate reaction
acid phosphatase), which infiltrate the bone marrow and spleen.
Patients are typically male, and onset of the disease is in the
fifth or sixth decade of life. Symptoms relate to pancytopenia,
with anemia requiring transfusions; and to neutropenia, characterized by
increased susceptibility to infections and increased bleeding tendencies. Some
patients may have symptoms from splenomegaly, which is present in
80% of patients at the time of diagnosis of hairy cell
leukemia. The cytopenias are due to a combination of bone marrow
replacement and secondary hypersplenism.
The standard therapy for hairy cell leukemia between 1960 and
1995 was splenectomy, but recent advances in pharmacotherapy have
superseded this surgical approach. First-line therapy is now treatment
with purine nucleoside analogs, primarily cladribine, with a complete
response rate of 80–90%. It has never been shown
that splenectomy offers survival benefit in this indolent disease,
and the operation should be reserved for palliation of splenomegaly
in patients who have failed treatment with cladribine and second-line
agent rituximab and α-interferon.
Gidron A et al: Hairy cell leukemia: towards a
curative strategy. Hematol Oncol Clin North Am 2006;20:1152.
Haberman TM, et al: Splenectomy, interferon, and treatments
of historical interest in hairy cell leukemia. Hematol Oncol Clin
North Am 2006;20:1075.
Riccioni R et al: Hairy cell leukemia. Curr Treat Options Oncol
Myelodysplastic syndromes are a heterogeneous group of clinical
hematopoietic stem cell disorders manifested by pancytopenias and
dysplasia of the bone marrow.
Pathologic changes include extensive bone marrow fibrosis, extramedullary hematopoiesis
in the spleen and liver, and a leukoerythroblastic blood reaction that
may evolve into acute myeloid leukemia over time.
The bone marrow is usually almost completely replaced by fibrous
tissue, although in some cases it is hyperplastic and fibrosis is
minimal. Extramedullary hematopoiesis develops mainly in the spleen,
liver, and long bones. Symptoms are attributable to anemia (weakness,
fatigue, dyspnea) and to splenomegaly (abdominal fullness and pain,
which may be severe). Pain over the spleen from splenic infarcts
is common. Spontaneous bleeding, fatigue, secondary infection, bone
pain, and a hypermetabolic state are frequent. Portal hypertension
develops in some cases as a result of fibrosis of the liver, greatly
increased splenic blood flow, or both.
Hepatomegaly is present in 75% of cases and splenomegaly
with a firm and irregular spleen in all cases. Striking changes
in the peripheral blood are referable to the combination of extramedullary
hematopoiesis and hypersplenism. Patients are uniformly anemic,
and red cells vary greatly in size and shape, many of them distorted
and fragmented. The white count is usually high (20,000–50,000/μL).
The platelet count may be elevated, but values less than 100,000/μL
are seen in 30% of cases due to secondary hypersplenism.
Bone marrow aspirates frequently result in a dry tap because marrow
is replaced with fibrosis. It was once incorrectly thought that the
spleen performed a crucial function of extramedullary hematopoiesis
in this disease and that splenectomy could be lethal. In fact, many
patients with myeloid metaplasia feel better if the massive spleen
is removed, and their hypersplenism is often corrected.
About 30% of patients are asymptomatic at the time of initial
diagnosis and require no therapy. When cytopenias and splenomegaly
produce symptoms, treatment is primarily supportive using transfusions,
androgenic steroids, antimetabolites, and hematopoietic growth factors
as indicated. Newer therapies include treatment with immunomodulatory
drugs such as thalidomide or antibodies to vascular endothelial growth
factor and tumor necrosis factor. A subset of patients with myeloid
metaplasia has a component of autoimmune hemolytic anemia, and in
this group of patients, immunosuppressive therapy may be beneficial.
Splenectomy is indicated in the following situations: (1) major
hemolysis unresponsive to medical management, (2) severe symptoms
of massive splenomegaly with mass effect of the spleen, (3) life-threatening
thrombocytopenia, and (4) portal hypertension with variceal hemorrhage.
This is one of the rare occasions when portal hypertension may be
cured by splenectomy.
Splenectomy in myeloid metaplasia is associated with a 7–10% death
rate and frequent complications often related to postsplenectomy
hepatic morbidity. Splenectomy best relieves symptoms of splenomegaly
and portal hypertension, but only about 75% of patients
get relief from anemia and thrombocytopenia. Younger patients with
normal platelet counts and symptoms are the best candidates for splenectomy
in idiopathic myelofibrosis.
Mesa R et al: Myeloproliferative disorder-associated
massive splenomegaly. Clin Adv Hematol Oncol 2008;6:278.
Mesa RA et al: Palliative goals, patient selection, and perioperative
platelet management: outcomes and lessons from 3 decades of splenectomy
for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer
Reilly JT et al: Idiopathic myelofibrosis: pathogenesis to treatment.
Hematol Oncol 2006;24:56.
Mast Cell Disease
Systemic mast cell disease, or mastocytosis, is a rare condition
characterized by mast cell infiltration of a number of tissues,
including the spleen. There are two types: indolent and aggressive.
In indolent systemic mass cell disease, there is no need for consideration
of splenectomy. The aggressive type is associated with hematologic
diseases with characteristics of lymphoma. Splenomegaly may occur,
with the predominant symptoms resulting from thrombocytopenia due
to hypersplenism. In this subgroup of patients with aggressive disease,
splenectomy improves platelet counts and is associated with longer
median survival time than for patients with aggressive disease who
do not undergo splenectomy, although systemic therapy including α-interferon
has been shown to be effective.
Hennessy B et al: Management of patients with
systemic mastocytosis: review of the M.D. Anderson Cancer Center
experience. Am J Hematol 2004;77:209.
Maalouf M et al: Portal vein thrombosis after laparoscopic splenectomy
for systemic mastocytosis: a case report and review of the literature.
Surgical Laparosc Endosc Percutan Tech 2008;18:219.
Metabolic disorders amenable to splenectomy are rare inherited
diseases that include as a component splenic enlargement due to
the pathologic deposition of material within the spleen. In Gaucher
disease, excess sphingolipid is deposited in the spleen. In sarcoidosis,
the spleen becomes involved with noncaseating granulomas, as can
be seen in lymph nodes. Inherited disorders also include disease
in which there is a specific immunologic target with associated
destruction in the spleen.
Gaucher disease is an autosomal recessive disorder characterized
by a deficiency in β-glucosidase, a lysosomal enzyme
that degrades the sphingolipid glucocerebroside. There is an increased
incidence of this disorder in Ashkenazi Jews. Three types of this
disease exist, and the one amenable to splenectomy is type I, or
the adult type. Pathologically, Gaucher disease results in lipid
accumulation within the white pulp of the spleen, the liver, or the
bone marrow. Predominant symptoms relate to massive splenomegaly either
from the direct effects of the size of the spleen or secondary to
cytopenias from hypersplenism.
Treatment by total splenectomy alleviates the symptoms but results
in accelerated hepatic and bone disease as well as a significant
increased risk of postsplenectomy infections. Treatment with partial
or subtotal splenectomy has been studied over the past 10 years
for both adults and children with Gaucher disease. Removing most
of the spleen corrects the symptoms of splenomegaly, but leaving
a splenic remnant provides a site for further deposition of lipid
that protects the liver and bone. The major problem with partial
splenectomy is the eventual recurrence and enlargement of the splenic
remnant accompanied by recurrent symptoms. As with hereditary spherocytosis,
there is an increased incidence of pigmented gallstones occurring in
up to two thirds of female patients and one third of male patients.
The goal of subtotal splenectomy in Gaucher disease is to leave
a small fragment approximately the size of the fist of the patient. Replacement
therapy with recombinant glucocerebrosidase enzyme has recently become
available, but the cost of chronic treatment is prohibitive.
Cox TM et al: Management of non-neuronopathic
Gaucher disease with special reference to pregnancy, splenectomy,
bisphosphonate therapy, use of biomarkers and bone disease monitoring.
J Inherit Metab Dis 2008;31:319.
Jmoudiak M et al: Gaucher disease: pathological mechanisms and
modern management. Br J Haematol 2005;129:178.
Wiskott-Aldrich syndrome is an X-linked disease characterized
by thrombocytopenia, combined B and T cell immunodeficiency, eczema,
and a propensity to develop malignancies. Thrombocytopenia is the
major feature of this rare disorder, with most patients presenting
with bloody diarrhea, epistaxis, and petechiae at a young age. Platelet
counts typically range between 20,000/μL
and 40,000/μL, and the platelets that
are present are between one fourth and one half of normal size.
The spleen sequesters and destroys platelets in this disease, releasing “microplatelets” back
into the circulation. The genetic defect in this disorder may be
related to an abnormal adhesion molecule affecting immune as well
as platelet cell-to-cell interaction.
Splenectomy in Wiskott-Aldrich syndrome was at one time withheld,
since the postoperative course was characterized by severe and fatal
infections due to the underlying immune defect of this disorder
combined with loss of the immune function of the spleen. However,
splenectomy does normalize platelet shape, size, and numbers, and
the use of prophylactic antibiotics after splenectomy has significantly
increased survival rates. The optimal treatment of Wiskott-Aldrich syndrome
is a human leukocyte antigen (HLA)-matched sibling bone marrow transplantation.
However, splenectomy with antibiotics results in better survival than
an unmatched bone marrow transplantation. Patients who do not undergo bone
marrow transplantation or splenectomy typically do not survive past
the age of 5 years.
Conley ME et al: An international study examining
therapeutic options used in the treatment of Wiskott-Aldrich syndrome. Clin
Verni W et al: The spleen in the Wiskott-Aldrich syndrome: histopathologic
abnormalities of the white pulp correlate with the clinical phenotype
of the disease. Am J Surg Pathol 1999;23:192.
Chédiak-Higashi syndrome is a rare autosomal recessive
disease characterized by immunodeficiency that increases the susceptibility
to bacterial and viral infections and is manifested by recurrent fever,
nystagmus, and photophobia. Most patients experience widespread infiltration
of tissues with histiocytes similar to a lymphoma. Secondary hepatosplenomegaly
with lymphadenopathy, leukopenia, and bleeding complications occur
in the accelerated phase of Chédiak-Higashi syndrome. Standard treatment
includes chemotherapy, steroids, and ascorbic acid, but these patients
have a poor prognosis. Splenectomy has been used in the accelerated phase
with beneficial results.
Dinauer MC et al: Disorders of neutrophil function.
Methods Mol Biol 2007;412:489.
Harfi HA et al: Chédiak-Higashi syndrome: clinical,
hematologic, and immunologic improvement after splenectomy. Ann
Sarcoidosis is a granulomatous disease of unknown origin that
can involve virtually any organ or area of the body. Pulmonary disease
is most common, but autopsy studies have shown that the spleen is
the second-most common site, with enlargement by noncaseating granulomas
in 50–60% of patients. However, most patients
do not have massive splenomegaly. When this does occur, patients
can have significant cytopenias related to hypersplenism as well
as the constitutional symptoms and hypercalcemia of sarcoidosis.
In this subgroup of patients, splenectomy is indicated as a potential
curative procedure for each of these symptoms.
Rodriguez-Garcia JL: Systemic sarcoidosis with
spleen involvement. Postgrad Med J 2001;77:265.
Xiao GQ et al: Asymptomatic sarcoidosis presenting as massive
splenomegaly. Am J Med 2002:113:698.
In this category of diseases, there is generally no intrinsic abnormality
of the spleen, as opposed to hypersplenism, in which the spleen
is primarily infiltrated by neoplasia or storage products and causes
cytopenias due to increased volume of splenic tissue. In the autoimmune
disorders, there is a humoral antibody response against proteins
on circulating blood cells, resulting in depletion primarily within
the spleen. Disorders involving platelets, erythrocytes, and neutrophils
are listed in decreasing order of incidence. Erythrocyte disorders
are genetic defects in structural components or hemoglobin that
increase the clearance of red cells in the spleen, causing a significant
decrease in erythrocyte half-life.
- Malaise, abdominal discomfort.
- Jaundice, anemia, splenomegaly.
- Spherocytosis, increased osmotic fragility of red cells, negative
Hereditary spherocytosis (congenital hemolytic jaundice, familial
hemolytic anemia), the most common congenital hemolytic anemia (affecting
1:5000 individuals), is transmitted as an autosomal dominant trait.
It is caused by a variety of genetic defects related to abnormal
cellular structural proteins, primarily ankyrin band 3, alpha and
beta spectrum, and protein 4-2, which alter binding of the cytoskeleton
to the cellular membrane, causing a decreased cellular plasticity with
membrane loss. The normal shape of the erythrocyte is changed from
a biconcave disk into a sphere, and the decreased membrane-to-cell
volume ratio causes a lack of deformability that delays passage
through the channels of the splenic red pulp. Significant cell destruction
occurs only in the presence of the spleen. Hemolysis is largely relieved
The condition is seen in all races but is more frequent in whites
than in blacks. When discovered early in infancy, it may resemble
hemolytic disease of the newborn due to ABO incompatibility. In
occasional instances, the diagnosis is not made until later in adult
life, but it is usually discovered in the first 3 decades.
The principal manifestations are splenomegaly, mild to moderate
anemia, and jaundice. The patient may complain of easy fatigability.
The spleen is almost always enlarged and may cause fullness and
discomfort in the left upper quadrant. However, most patients are
diagnosed during a family survey at a time when they are asymptomatic.
Periodic exacerbations of hemolysis can occur. The rare hypoplastic
crises, which often follow acute viral illnesses, may be associated
with profound anemia, headache, nausea, abdominal pain, pancytopenia,
and hypoactive marrow.
The red cell count and hemoglobin are moderately reduced. Some
of the asymptomatic patients detected by family surveys have normal
red cell counts when first seen. The red cells are usually normocytic,
but microcytosis may occur. Macrocytosis may present during periods of
marked reticulocytosis. Spherocytes in varying numbers, sizes, and
shapes are seen on a Wright-stained smear. The reticulocyte count
is increased to 5–20%.
The indirect serum bilirubin and stool urobilinogen are usually
elevated, and serum haptoglobin is usually decreased to absent.
The Coombs test is negative. Osmotic fragility is increased; hemolysis of
5–10% of cells may be observed at saline concentrations
of 0.6%. A more accurate reflector of fragility is the
cryohemolysis test, which has a sensitivity and specificity of almost
95% for spherocytosis. Occasionally, the osmotic fragility
is normal but the incubated fragility test (defibrinated blood incubated
at 37 °C for 24 hours) will show increased hemolysis. Autohemolysis
of defibrinated blood incubated under sterile conditions for 48
hours is usually greatly increased (10–20%, compared
to a normal value of < 5%). The addition of 10% glucose before
incubation will decrease the abnormal osmotic fragility and autohemolysis.
Infusion of the patient’s own blood labeled with 51Cr
shows a greatly shortened red cell life span and sequestration in
the spleen. Normal red cells labeled with 51Cr have a normal
life span when transfused into a spherocytotic patient, indicating
that splenic function is normal.
At present, there is no pathognomonic test for hereditary spherocytosis, although
the cryohemolysis test is very promising. Spherocytes in large numbers may
occur in autoimmune hemolytic anemias, in which osmotic fragility
and autohemolysis may be increased but are usually not improved
by incubation with glucose. The positive Coombs test, negative family
history, and sharply reduced survival of normal donor red cells
are diagnostic of autoimmune hemolysis. Spherocytes are also seen
in hemoglobin C disease, in some alcoholics, and in some severe
Pigment gallstones occur in about 85% of adults with
spherocytosis but are uncommon under age 10. On the other hand, gallstones
in a child should suggest congenital spherocytosis.
Chronic leg ulcers unrelated to varicosities are a rare complication
but, when present, will heal only after the spleen is removed.
Splenectomy is the sole treatment for hereditary spherocytosis
and is indicated even when the anemia is fully compensated and the
patient is asymptomatic. The longer the hemolytic process persists,
the greater the potential risk of complications such as hypoplastic
crises and cholelithiasis. At operation, the gallbladder should
be inspected for stones and accessory spleens should be sought.
When there is associated cholelithiasis, cholecystectomy should be
performed along with the splenectomy. Unless the clinical manifestations are
severe, splenectomy should be delayed in children until age 6 to
avoid the risk of increased infection due to loss of reticuloendothelial
function. For children under age 5 with severe disease and high
transfusion requirements, a partial (80%) splenectomy may
correct symptoms while maintaining the normal immune functions of
Splenectomy cures the anemia and jaundice in all patients. The
membrane abnormality, spherocytosis, and increased osmotic fragility
persist, but red cell life span becomes almost normal. An overlooked
accessory spleen is an occasional cause of failure of splenectomy.
The presence of Howell-Jolly bodies in red cells makes the presence of
accessory spleens unlikely.
Diesen DL et al: Partial splenectomy for children
with congenital hemolytic anemia and massive splenomegaly. J Pediatr
Tracy ET et al: Partial splenectomy for hereditary spherocytosis.
Pediatr Clin North Am 2008;55:503.
This autosomal dominant genetic disorder, also known as ovalocytosis,
is usually of little clinical significance. Normally, up to 15% oval
or elliptic red blood cells can be seen on a peripheral blood smear.
In elliptocytosis, at least 25% and up to 90% of
circulating erythrocytes are elliptic. As with hereditary spherocytosis, this
disease is due to a variety of genetic defects in cytoskeletal proteins
such as spectrin. The predominant abnormality is that this structural
protein exists as a dimer instead of a tetramer, leading to change
in the erythrocyte’s shape, decreased plasticity, and a
shortened life span of the cell.
Most affected individuals are asymptomatic; about 10% have
clinical manifestations consisting of moderate anemia, slight jaundice,
and a palpable spleen.
Symptomatic patients should have splenectomy and, if gallstones
are present, cholecystectomy. The red cell defect persists after
splenectomy, but the hemolysis and anemia are cured.
Gallagher PG: Update on the clinical spectrum
and genetics of red blood cell membrane disorders. Curr Hematol
Silveira P et al: Red blood cell abnormalities in hereditary
elliptocytosis and their relevance to variable clinical expression. Am
J Clin Pathol 1997;108:391.
Nonspherocytic Hemolytic Anemia
This is a heterogeneous group of rare hemolytic anemias caused
by inherited intrinsic red cell defects that lead to oxidative hemolysis.
Included in the group are pyruvate kinase deficiency and glucose
6-phosphate dehydrogenase (G6PD) deficiency. They are usually manifested
in early childhood with anemia, jaundice, reticulocytosis, erythroid hyperplasia
of the marrow, and normal osmotic fragility. As with other hemolytic anemias,
there may be associated cholelithiasis.
Multiple blood transfusions are often required. Splenectomy,
while not curative, may ameliorate some of these conditions, especially
pyruvate kinase deficiency. In G6PD deficiency, splenectomy is not
beneficial, and treatment consists of avoidance of dietary oxidants.
Baronciani L et al: Hematologically important
mutations: red cell pyruvate kinase. Blood Cells Mol Dis 1998;24:273.
Major (Mediterranean Anemia; Cooley Anemia)
In the most common form of this autosomal dominant disorder,
a structural defect in the β-globin chain causes excess α chains
to precipitate on the inner surface of the membrane of the erythrocyte
and produces abnormal red cells (eg, target cells). Heterozygotes
usually have mild anemia (thalassemia minor); however, starting
early in infancy, homozygotes have severe chronic anemia accompanied
by jaundice, hepatosplenomegaly (often massive), retarded body growth, and
enlargement of the head. The peripheral blood smear reveals target cells,
nucleated red cells, and a hypochromic microcytic anemia. Gallstones are
present in about 25% of patients. A characteristic feature
is the persistence of fetal hemoglobin (Hb F).
Since the anemia of thalassemia is due to both increased destruction
of red cells and decreased hemoglobin production, splenectomy does
not cure the anemia, as in spherocytosis, but it may reduce transfusion
requirements by removing an enlarged, uncomfortable spleen. Treatment
is by iron chelation and transfusion.
Aessopos A et al: Cardiovascular effects of splenomegaly
and splenectomy in beta-thalassemia. Ann Hematol 2005;84:353.
Konstadoulakis MM et al: Laparoscopic versus open splenectomy
in patients with beta thalassemia major. J Laparoendosc Adv Surg
Tech A 2006;16:5.
The production of IgG autoantibodies specific for cell membrane
proteins on erythrocytes causes autoimmune hemolytic anemia; on
platelets, it causes idiopathic thrombocytopenic purpura (ITP) and
may cause neutropenia in Felty syndrome. Macrophages express Fc
receptors for IgG, and antibody-coated cells that pass through the splenic
sinuses of the red pulp come into contact with these phagocytic
cells. Furthermore, the microenvironment of the red pulp with slow
flow of blood with a high cellular content through circuitous spaces
facilitates opsonization of cells in the spleen. Production of autoantibodies in
the white pulp germinal centers may also enhance cellular destruction,
particularly in ITP. Understanding this pathophysiologic mechanism
is important, since autoimmune hemolytic anemia caused by IgM autoantibodies
(ie, cold agglutinin hemolytic anemia) does not respond to splenectomy
because macrophages do not have Fc receptors for IgM. This mechanism
also explains why treatment with high-dose intravenous immune globulin
is beneficial in these diseases because it blocks the macrophage
- Fatigue, pallor, jaundice.
- Persistent anemia and reticulocytosis.
The autoimmune hemolytic anemias have also been
classified according to the optimal temperature at which autoantibodies
react with the red cell surface (warm or cold antibodies). This
classification is particularly useful, since patients with cold
antibodies will not benefit from splenectomy but those with warm
Although hemolysis without demonstrable antibody (negative Coombs
test) may occur in uremia, cirrhosis of the liver, cancer, and certain
infections, in most cases the red cell membranes are coated with
either immunoglobulin or complement (positive Coombs test). The
antibody in IgG autoimmune hemolytic anemia is specifically directed
against the Rh locus on the erythrocyte. Initiation of this disease
is either idiopathic (40–50%) or secondary to
drug exposure, connective tissue disorders, or lymphoproliferative
disorders. Hemolytic anemia due to cold antibodies is less common
and always a secondary immune response. Cold agglutinin hemolytic
anemia is due typically to an IgM directed against the I red cell
antigen, and hemolysis occurs intravascularly by complement fixation
and not within the spleen making splenectomy not beneficial in the
setting of cold antibodies.
About 20% of cases of secondary immune hemolytic anemia
are due to drug use, and hemolysis is usually mediated by warm antibodies.
Penicillin, quinidine, hydralazine, and methyldopa have been most
commonly implicated in this syndrome (Table 27–3).
Table 27–3. Disorders Associated with Immune Hemolysis. |Favorite Table|Download (.pdf)
Table 27–3. Disorders Associated with Immune Hemolysis.
|Immune drug reaction (penicillin, quinidine, hydralazine,
|Collagen vascular disease (lupus erythematosus, rheumatoid arthritis)|
|Tumors (lymphoma, myeloma, leukemia, dermoid cysts, ovarian
|Infection (Mycoplasma, malaria, syphilis,
Autoimmune hemolytic anemia may be encountered at any age but
is most common after age 50; it occurs twice as often in women.
The onset is usually acute, consisting of anemia, mild jaundice,
and sometimes fever. The spleen is palpably enlarged in over 50% of
patients, and pigment gallstones are present in about 25%.
Rarely, a sudden severe onset produces hemoglobinuria, renal tubular necrosis,
and a 40–50% death rate.
Hemolytic anemia is diagnosed by demonstrating a normocytic normochromic anemia,
reticulocytosis (over 10%), erythroid hyperplasia of the
marrow, and elevation of serum indirect bilirubin. Stool urobilinogen
may be greatly increased, but there is no bile in the urine. Serum haptoglobin
is usually low or absent. The direct Coombs test is positive because the
red cells are coated with immunoglobulins or complement (or both).
Associated diseases must be carefully sought and appropriately
treated. For drug-induced secondary hemolytic anemia, further exposure
to the offending agent must be terminated. Corticosteroids produce
a remission in about 75% of patients, but only 25% of
remissions are permanent. Transfusion should be avoided if possible,
since crossmatching may be extremely difficult, requiring washed
red cells and saline-active antisera. Rituximab is an effective
second-line therapy now producing durable responses 40% of
steroid resistant cases.
Splenectomy is indicated for patients with warm-antibody hemolysis
who fail to respond to 4–6 weeks of high-dose corticosteroid
therapy, for patients who relapse after an initial response when steroids
are withdrawn, and for patients in whom steroid therapy is contraindicated
(eg, those with active pulmonary tuberculosis). Patients who require chronic
high-dose steroid therapy should also be considered for splenectomy, since
the risks of long-term steroid administration are substantial.
Splenectomy is effective because it removes the principal site
of red cell destruction. Occasionally, splenectomy identifies the
presence of an underlying disorder such as lymphoma. About half of
patients who fail to respond to splenectomy will respond to azathioprine
or cyclophosphamide. Plasmapheresis has been employed as salvage
therapy in patients with refractory hemolytic anemia.
Relapses may occur after splenectomy but are less frequent if
the initial response was good. The ultimate prognosis in the secondary
cases depends on the underlying disorder.
Packman CH et al: Hemolytic anemia due to warm
autoantibodies. Blood Rev 2008;22:17.
Valent P et al: Diagnosis and treatment of autoimmune haemolytic
aneaemias in adults: a clinical review. Wien Klin Wochenschr 2008;120:136.
Purpura (Idiopathic Thrombocytopenic Purpura, ITP)
- Petechiae, ecchymoses, epistaxis, easy bruising.
- No splenomegaly.
- Decreased platelet count, prolonged bleeding time, poor clot
retraction, normal coagulation time.
Immune thrombocytopenic purpura is a hemorrhagic syndrome with
diverse causes that can occur in an acute or chronic form and is
characterized by marked reduction in the number of circulating platelets,
abundant megakaryocytes in the bone marrow, and a shortened platelet
life span. It may be idiopathic or secondary to a lymphoproliferative
disorder, drugs or toxins, bacterial or viral infection (especially
in children), systemic lupus erythematosus, or other conditions.
Although responses to corticosteroids and to splenectomy in these
patients are comparable to the responses observed in other patients with
immune thrombocytopenic purpura, splenectomy should be reserved
for those with signs of blood loss, since surgical complications
are high and survival may be short. However, due to the incidence
of ITP, this disease is typically the most common indication for
splenectomy in most institutional series.
The pathogenesis of both primary and secondary disorders involves
a circulating antiplatelet IgG autoantibody usually directed against
a membrane protein, which is the fibrinogen receptor (glycoprotein
IIb/IIIa). In this disorder, the spleen is primarily the
site of platelet destruction and may also be a significant source
of autoantibody production. Splenomegaly, present in only 2% of
cases, is usually a manifestation of another underlying disease
such as lymphoma or lupus erythematosus. Of HIV-positive patients, 5–15% have
thrombocytopenia independent of the immunologic state of their disease
that is clinically indistinguishable from typical chronic ITP. The
precise pathophysiologic mechanism in relation to HIV infection
is not known.
The onset may be acute, with ecchymoses or showers of petechiae,
and may be accompanied by bleeding gums, vaginal bleeding, gastrointestinal
bleeding, and hematuria. Central nervous system bleeding occurs
in 3% of patients. The acute form is most common in children, usually
occurring before 8 years of age, and often begins 1–3 weeks
after a viral upper respiratory illness.
The chronic form, which may start at any age, is more common
in women. It characteristically has an insidious onset, often with
a long history of easy bruisability and menorrhagia. Showers of
petechiae may occur, especially over pressure areas. Cyclic remissions
and exacerbations may continue for several years.
The platelet count is moderately to severely decreased (always
below 100,000/μL), and platelets may be
absent from the peripheral blood smear. Although white and red cell
counts are usually normal, iron deficiency anemia may be present as
a result of bleeding. The bone marrow shows increased numbers of
large megakaryocytes without platelet budding.
The bleeding time is prolonged, capillary fragility (Rumpel-Leede
test) greatly increased, and clot retraction poor. Partial thromboplastin
time, prothrombin time, and coagulation time are normal. Specific
determinations of antiplatelet antibody titers can now be routinely assessed
to aid in diagnosis. Reduced red cell or platelet survival can be
measured by labeling the patient’s cells with 51Cr
or the platelets with indium-111 and measuring the rate of disappearance
of radioactivity from the blood. The spleen’s role in producing
the anemia or thrombocytopenia can be determined by measuring the
ratio of radioactivity that accumulates in the liver and spleen
during destruction of the tagged cells; a spleen–liver
ratio greater than 2:1 indicates significant splenic pooling and
suggests that splenectomy would be beneficial.
Other causes of nonimmunologic thrombocytopenia must be ruled
out, such as leukemia, aplastic anemia, and macroglobulinemia. Thrombocytopenia
and purpura may be caused by ineffective thrombocytopoiesis (eg,
pernicious anemia, preleukemic states) or by nonimmune platelet
destruction (eg, septicemia, disseminated intravascular coagulation,
or other causes of hypersplenism).
Treatment of immune thrombocytopenic purpura depends on the age
of the patient, the severity of the disease, the duration of the
thrombocytopenia, and the clinical variant. Secondary immune thrombocytopenias
are best managed by treating the underlying primary disorder (eg,
if it is drug-induced, the drug should be stopped).
Patients with mild or no symptoms need no specific therapy but
should avoid contact sports, elective surgery, and all unessential
medications. Corticosteroids are indicated in patients with moderate
to severe purpura of short duration. Usually, 60 mg of prednisone
(or equivalent) is required daily; this is continued until the platelet
count returns to normal and then is gradually tapered after 4–6
weeks. Corticosteroids produce a response in 70–80%,
but sustained remissions in only 20% of adults. Second-line
therapy with rituximab improves platelet counts in 30–40% of
patients and sustained complete response in 10–20%.
New agents to stimulate platelet production such as thrombopoietin
(TPO) against AMG531 and eltrombopag are being studied as third-line
Splenectomy is the most effective form of therapy and is indicated
for patients who do not respond to corticosteroids, for those who
relapse after an initial remission on steroids, and for steroid-dependent
patients. Corticosteroid therapy is not necessary in the immediate
preoperative period unless bleeding is severe or the patient was
receiving steroids before the operation. If indicated, platelet
transfusions are given intraoperatively only after ligation of the
splenic artery or removal of the spleen, since platelets from earlier
transfusion would be rapidly sequestered in the spleen. For temporary
treatment of the thrombocytopenia, intravenous immunoglobulin (IGIV)
Splenectomy produces a sustained remission in about 68% of
patients. As with corticosteroids, success rates are better with
acute than chronic immune thrombocytopenic purpura. Two factors associated
with better outcomes are shorter duration of disease and younger age.
The platelet count usually rises promptly following splenectomy
(eg, it may double in 24 hours) and reaches a peak after 1–2
weeks. If the platelet count remains elevated after 2 months, the
patient can be considered cured. When corticosteroids and splenectomy have
failed, immunosuppressive drugs (azathioprine, vincristine) will
achieve a remission in 25% of cases.
The benefit of splenectomy for HIV-associated ITP has been less
clear. The risk of infection and the overall shortened survival
in this population argue against splenectomy. However, in HIV patients without
AIDS, clinically significant thrombocytopenia responds completely
in 70%, and there is partial improvement in 20% following
splenectomy. Splenectomy does not appear to alter the overall natural
history of HIV infection.
Acute immune thrombocytopenic purpura in children under age 16
has an excellent prognosis; approximately 80% of patients
have a complete and permanent spontaneous remission. This occurs rarely
in adults. Splenectomy is successful in about 80% of patients,
but more often in idiopathic cases than in those secondary to another
disorder. The proportion of patients undergoing splenectomy for
ITP has decreased due to medical treatment other than steroids that
have efficacy, although the incidence of chronic ITP has increased.
Agents to stimulate thrombopoietin may have significant benefit
for patients who have no improvement in platelet count after splenectomy.
Arnold DM et al: Current options for the treatment
of idiopathic thrombocytopenic purpura. Semin Hematol 2007;44:512.
Cooper N et al: Should rituximab be used before or after splenectomy
in patients with immune thrombocytopenic purpura? Curr Opin Hematol
Dolan JP et al: Splenectomy for immune thrombocytopenic purpura.
Am J Hematol 2008;83:93.
Godeau B et al: Rituximab efficacy and safety in adult splenectomy
candidates with chronic immune thrombocytopenic purpura: results
of a prospective multicenter phase 2 study. Blood 2008;112:999.
Kuter DJ et al: Efficacy of romiplostim
in patients with chronic
immune thrombocytopenic purpura: a double-blind randomized controlled
trial. Lancet 2008;371:395.
Neunert CE et al: Severe chronic refractory immune thrombocytopenic
purpura during childhood: a survey of physician management. Pediatr
Blood Cancer 2008;51:513.
Newland W et al: Emerging strategies to treat chronic immune
thrombocytopenic purpura. Eur J Haematol 2008;69:27.
Rodeghiero F et al: First-line therapies for immune thrombocytopenic
purpura: re-evaluating the need to treat. Eur J Haematol 2008;69:19.
Shojaiefard A et al: Prediction of response to splenectomy in
patients with idiopathic thrombocytopenic purpura. World J Surg
Stasi R et al: Idiopathic thrombocytopenic purpura: current
concepts in pathophysiology and management. Thromb Haemost 2008;99:4.
Tarantino MD et al: Update on the management of immune thrombocytopenic purpura
in children. Curr Opin Hematol 2007;14:526.
Approximately 1% of patients with rheumatoid arthritis
have splenomegaly and neutropenia—a triad known as Felty
syndrome. High levels of IgG have been identified on the surface
of neutrophils with evidence of increased of granulopoiesis in the
bone marrow. Pathologic analysis of the spleen in Felty syndrome patients
shows a larger proportionate increase in the white pulp as opposed
to most conditions of splenomegaly. There is evidence of excess
accumulation of neutrophils in both the T cell zone of the white
pulp as well as the cord and sinuses of the red pulp.
Patients with severe neutropenia have clinical symptoms of recurring
infections in Felty syndrome. Symptomatic patients who have evidence
of IgG on the surface of neutrophils should be considered for splenectomy.
Neutropenia will improve in 60–70% of these patients,
but relapse of neutropenia as well as recurrent infections in the
presence of normal neutrophil counts may occur, and these untoward
events have dampened enthusiasm for splenectomy in this disease.
Balint GP, Balint PV: Felty’s syndrome.
Best Pract Res Clin Rheumatol 2004;18:631.
Burks EJ, Loughran TP: Pathogenesis of neutropenia in large
granular cells leukemia and Felty’s syndrome. Blood Rev 2006;20:265.
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with
a pentad of clinical features: (1) fever, (2) thrombocytopenic purpura,
(3) hemolytic anemia, (4) neurologic manifestations, and (5) renal
failure. The cause is unknown, but autoimmunity to endothelial cells
or a primary platelet defect has been implicated, and its occurrence
in patients with AIDS has been reported. It is most common between
ages 10 and 40 years.
The thrombocytopenia is probably due to a shortened platelet
life span. The microangiopathic hemolytic anemia is produced by
passage of red cells over damaged small blood vessels containing fibrin
strands. Rigid red cells are trapped and fragmented in the spleen,
whereas those that escape the spleen may be more vulnerable to damage
and destruction in the abnormal microvasculature. The anemia is
often severe, and it may be aggravated by hemorrhage secondary to
thrombocytopenia. Hepatomegaly and splenomegaly occur in 35% of cases.
Until recently, there was no effective therapy for this disorder,
and mortality rates as high as 95% were reported. Most
patients died of renal failure or cerebral bleeding. Plasmapheresis
with plasma exchange has recently emerged as an effective form of
treatment that is superior to simple plasma infusion with complete
response rate of 55–65%. Plasma exchange failure
can be salvaged with splenectomy with 60% having a substantial
response and a 20–30% relapse rate.
Kappers-Klunne MC et al: Splenectomy for the treatment
of thrombotic thrombocytopenic purpura. Br J Haematol 2005; 130:768.
Outschoorn UM et al: Outcomes in the treatment of thrombotic
thrombocytopenic purpura with splenectomy: a retrospective cohort
study. Am J Hematol 2006;81:895.
of the Spleen
Vascular disease of the spleen treated by splenectomy can occur
both with the arterial inflow and the venous outflow. The most common
disease is splenic vein thrombosis; this can be treated in a straightforward
manner by splenectomy. Splenic artery aneurysms are one of the most
common sites of visceral aneurysms and may require splenectomy.
Thrombosis of the splenic vein can occur as an isolated event not
due to any pathologic findings in the spleen but due to diseases
that impact the splenic vein as it travels along the superior border
of the pancreas. The most common cause is acute or chronic pancreatitis
or a pseudocyst of the body/tail of the pancreas, with
the general inflammatory reaction in the pancreas resulting in thrombosis
of the splenic vein in 20% of patients. Inflammation from
a posterior gastric ulcer is another cause. Direct extension of
carcinoma of the pancreas or stomach into the lesser sac may cause
splenic vein thrombosis, but the diagnosis is generally not subtle
because of other manifestations of these malignancies. Idiopathic retroperitoneal
fibrosis may be an alternative cause of splenic vein thrombosis.
Splenic vein thrombosis presents as upper gastrointestinal hemorrhage
due to isolated gastric varices. With occlusion of the splenic vein,
outflow of blood from the spleen is diverted into the short gastric
veins as the remaining collateral vessels. These veins dilate and
become varices primarily in the fundus of the stomach, resulting
in bleeding in 15–20% of patients.
Splenic vein thrombosis is suspected when there are isolated
varices of the stomach particularly in the proximal greater curvature
without any esophageal varices. Since there is no portal hypertension,
there are no associated signs or symptoms of cirrhosis. Definitive diagnosis
is made by confirming that there is no blood flow in the main splenic vein.
Invasive venography is no longer needed because this diagnosis can
be confirmed by CT scan or MRI scans with contrast material or by
high-resolution ultrasound. CT or MRI is preferred because the splenic
vein may be hidden from ultrasound by bowel gas, and CT or MRI allows
characterization of the surrounding structures (pancreas, stomach) to
assess for causative pathology.
Splenectomy is curative in patients with splenic vein thrombosis.
All of the symptoms relate to increased splenic blood flow through
collateral vessels; eliminating that blood flow is curative. If
a splenic vein thrombosis is diagnosed—even if the patients
have not had an episode of upper gastrointestinal hemorrhage—an elective
or prophylactic splenectomy is indicated if the patients are otherwise healthy.
In patients with portal vein thrombosis, the magnitude of the disease
and associated problems is greatly amplified, and splenectomy is
almost never indicated because it is not curative.
Agarwal AK et al: Significance of splenic vein
thrombosis in chronic pancreatitis. Am J Surg 2008;196:149.
Tumors of the Spleen
Parasitic cysts are almost always echinococcal. They may be asymptomatic,
but usually the patient notices splenomegaly. Calcification of the
cyst wall may be seen on x-ray. Eosinophilia may be found, and serologic
tests may confirm the diagnosis. The treatment of choice is splenectomy.
Other cysts are dermoid, epidermoid, endothelial, and pseudocysts.
The latter are thought to be late results of infarction or trauma.
Splenectomy may be indicated to exclude tumor; however, partial splenectomy
or observation has been advocated.
The rare primary tumors of the spleen include lymphoma, sarcoma,
hemangioma, and hamartoma. Hamartomas may be confused grossly with
splenic lymphoma at laparotomy. These lesions are usually asymptomatic
until splenomegaly causes abdominal discomfort or a palpable mass.
The benign vascular tumors of the spleen (angiomas) can produce hypersplenism.
Spontaneous rupture with massive hemorrhage can occur. Splenectomy
is indicated if the tumor appears to be limited to the spleen. Inflammatory
pseudotumors are benign lesions composed of a mixture of inflammatory
cells and a granulomatous reaction that can occur in a variety of
organs, including the spleen. Constitutional symptoms of lethargy,
weight loss, and fatigue occur and can be alleviated by splenectomy.
The spleen is a common site for metastases in advanced cancers,
especially of the lung and breast and melanoma. Splenic metastases
are common autopsy findings but are rarely clinically significant.
Atmatzidis K et al: Splenectomy versus spleen-preserving
surgery for splenic echinococcosis. Dig Surg 2003;20:527.
Kraus MD, Fleming MD, Vonderheide RH: The spleen as a diagnostic
specimen: a review of 10 years’ experience at two tertiary
care institutions. Cancer 2001;91:2001.
Mackenzie RK, Youngson GG, Mahomed AA: Laparoscopic decapsulation
of congenital splenic cysts: a step forward in splenic preservation.
J Ped Surg 2004;39:88.
Wu HM et al: Management of splenic pseudocysts following trauma:
a retrospective case series. Am J Surg 2006;191:631.
Yu RS, Zhang SZ, Hua JM: Imaging findings of splenic hamartoma.
World J Gastroent 2004;10:13.
the Spleen (Splenic Abscess)
Splenic abscesses are uncommon but are important because the
death rate ranges between 40% and 100%. They may
be caused by hematogenous seeding of the spleen with bacteria from remote
sepsis such as endocarditis, by direct spread of infection from
adjacent structures, or by splenic trauma resulting in a secondarily
infected splenic hematoma. Splenic abscess is a complication of
intravenous drug abuse. In 80% of cases, one or more abscesses
exist in organs other than the spleen, and the splenic abscess develops
as a terminal manifestation of uncontrolled sepsis in other organs.
Enteric organisms are found in over two thirds of splenic abscesses,
with staphylococci and nonenteric streptococci comprising the majority
of the remainder. In some patients, unexplained sepsis, progressive
splenic enlargement, and abdominal pain are the presenting manifestations. The
spleen may not be palpable, because of left upper quadrant tenderness
and guarding. A left pleural effusion combined with unexplained
leukocytosis in a septic patient suggests a splenic abscess. The
finding of gas in the spleen on plain abdominal x-ray is pathognomonic
of splenic abscess, but CT scan is the optimal way to define and
diagnose a splenic abscess.
Most splenic abscesses remain localized, periodically seeding
the bloodstream with bacteria, but spontaneous rupture and peritonitis
may occur. Splenectomy is essential for cure if sepsis is localized
to the spleen. Percutaneous drainage of large, solitary juxtacapsular abscesses
may occasionally be feasible but is associated with an extremely
high mortality rate and should be reserved for patients unable to
withstand an operation.
Tung CC et al: Splenic abscess: an easily overlooked
disease? Am Surg 2006;72:322.
One indication for splenectomy is for diagnosis in an otherwise
asymptomatic patient. Splenectomy may be needed to make a diagnosis
when an asymptomatic mass lesion is seen within the spleen on CT
scan, ultrasound, or MRI scan for which a definitive diagnosis cannot
be made radiographically. Another example is when a patient has
either a palpable spleen on physical examination or an enlarged
spleen by scan, and otherwise has no clear diagnostic disorder.
For the patients who have an isolated splenic mass, 60% turned
out to be malignant lesions and 40% turned out to be benign
lesions. Most malignant lesions are lymphoma; the next most common
is metastatic carcinomas, including some in which the primary diagnosis
had not been made previously. In patients with benign lesions, more than
half were cysts, and there were also splenic hamartomas and splenic
In diagnosing an isolated splenic mass, most of these lesions
can be diagnosed by doing a fine-needle aspiration biopsy. Certain
lesions—such as the cystic lesions or hemangioma—have
classic appearance on gadolinium-enhanced MRI scan, and these scans
are another imaging modality that could be utilized to sort out
mass lesions without tissue biopsy. PET scans will reliably identify high-grade
lymphoma and metastatic tumors but may miss low-grade or mantle
zone lymphoma. The risk of bleeding is significant in patients with
hemangiomas. These benign tumors of endothelial cells can be definitively
diagnosed with gadolinium-enhanced MRI, and this imaging test is
optimal for characterizing an isolated splenic mass.
Without a Diagnosis
The second diagnostic indication for splenectomy is unexplained
splenomegaly. Most of these enlarged spleens will be shown to have
lymphoma. The minority will have benign diagnoses including benign
lymphoid proliferation, benign vascular lesions, and granulomatous
disease, as well as splenic infarction and hemorrhage. The role
of the fine-needle aspiration and other percutaneous biopsies for
nondiagnosed splenomegaly is quite limited with no distinct mass
to biopsy; there would be very low yield in terms of being able
to make that diagnosis by that form of biopsy.
for Hodgkin Disease
Another type of diagnostic procedure is a staging laparotomy
for Hodgkin disease. Discussion of this procedure is more of a historical
note because it has limited use in today’s current practice
in treating this form of lymphoma.
A standard practice for pathologic staging between 1960 and 1990
was performance of a staging laparotomy in most patients with Hodgkin
disease. The reason for performing this invasive procedure was based
on reports that laparotomy altered the clinical stage of disease
in approximately 35% of patients. There are several reasons
why the incidence of performing staging laparotomy has decreased
over the past 10–15 years. The primary reason is that it
does not alter treatment of Hodgkin disease, according to results
of recent clinical series. Since systemic chemotherapy treats the
whole patient, accurate pathologic staging makes no impact on the treatment
outcome or treatment decisions.
Kraus MD, Fleming MD, Vonderheide RH: The spleen
as a diagnostic specimen: a review of 10 years’ experience
at two tertiary care institutions. Cancer 2001;91:2001.
Rose AT et al: The incidence of splenectomy is decreasing: lessons
learned from trauma experience. Am Surg 2000;66:481.
Rutherford SC et al: FDG-PET in prediction of splenectomy findings
in patients with known or suspected lymphoma. Leuk Lymphoma 2008;49:719.
Procedures in which mobilization of the left upper quadrant is
done (such as reflection of the spleen and pancreas medially to
expose retroperitoneal tissue, left adrenalectomy, and left nephrectomy)
put the spleen at risk for injury during the dissection. Simple
mobilization of the splenic flexure of the colon can lead to bleeding
from the inferior pole of the spleen that may be difficult to control.
The ligaments that go directly from the omentum to the capsule of
the spleen may be the most common cause of iatrogenic splenic trauma,
as it is a common practice to aggressively retract the omentum as needed
for exposure. If there are direct branches that sometimes may be
sizable from the omentum to the splenic capsule, this could lead
to capsular disruption and troublesome bleeding. A national database
on antireflux procedures of 86,411 patients reported an incidence
of iatrogenic splenectomy of 2.3%, which translates into
1987 iatrogenic splenectomies for that indication alone over a 6-year
period. An outcome study for colon cancer of 42,000 reported iatrogenic
splenectomy in less than 1% of all patients but 6% of
colon cancers at the splenic flexure. Splenectomy had a significant
increase in length of stay and a 40% increase in morbidity.
A recent series listed 73 iatrogenic splenectomies over a 10-year
period, or an average of 7 per year. This comprised 8.1% of
all splenectomies performed during that time interval. There are
probably several times that number of minor or moderate injuries
to the spleen during unrelated operations in which the spleen was
not removed but was repaired or salvaged. Just as in trauma to the
spleen, the techniques of splenorrhaphy can be employed to preserve
the spleen. A recent report indicates that use of a mesh wrap splenorrhaphy,
even in the setting of bowel surgery, does not lead to an increased
incidence of infection. For minor capsular disruption, the use of
the argon beam coagulator for surface cautery is a helpful technique.
The primary teaching point regarding iatrogenic injuries is that
the best way to preserve the spleen is to not damage it in the first
place. This requires caution in mobilizing tissue in and around
the spleen as well as visual inspection of the attachments of the
spleen prior to blunt mobilization. Whenever possible, attempts
should be made to preserve the spleen to decrease the risk of postsplenectomy
Berry MF, Rosato EF, Williams NN: Dexon mesh splenorrhaphy for
intraoperative splenic injuries. Am Surg 2003;69:176.
Cassar K, Munro A: Iatrogenic splenic injury. J Roy Coll Surg
Flum DR et al: The nationwide frequency of major adverse outcomes
in antireflux surgery and the role of surgeon experience. J Am Coll
McGory ML et al: The significance of inadvertent splenectomy
during colorectal cancer resection. Arch Surgery 2007;142:668.
In a recent large series evaluating reasons for splenectomy from
tertiary institutions, the single-most common indication for splenectomy
was as an incidental procedure on operations on an adjacent organ.
In these situations, the spleen needs to be removed either for completeness
of resection or because of division of the splenic vasculature The actual
primary treatments of those various disease entities in adjacent
organs are subjects of multiple other chapters within this textbook,
but a few comments need to be made regarding the reasons for splenectomy
and whether splenic preservation procedures are possible.
One common indication for an incidental splenectomy is to remove
tumors located in the distal pancreas. For decades, it was standard
practice to remove the spleen when removing the body and tail of
the pancreas because the splenic vein is intimately associated with
the distal pancreas. Because of the interest in splenic preservation
due to the incidence of postsplenectomy infection, operations have
been developed to remove the distal pancreas without removing the spleen.
The more technically challenging operation is a distal pancreatectomy
with preservation of the splenic artery and vein. A second spleen-preserving
distal pancreatectomy involves ligation of the splenic artery and
vein but preservation of short gastric vessels and utilizing those
vessels as collateral inflow and outflow to maintain splenic viability. Removal
of the distal pancreas with splenic preservation has also been recently
reported as a laparoscopic procedure. For patients with tumors that mandate
removal of the lymph nodes of the splenic hilum or with direct association
of the tumor with splenic parenchyma, certainly it is more appropriate
to do an operation based on neoplastic principles and perform a
distal pancreatectomy/splenectomy. In other indications,
if the anatomy is appropriate and the completeness of tumor resection
is not compromised, splenic preservation is certainly possible.
Additional procedures in which it is common to perform a splenectomy
include proximal gastric cancers. The importance of complete nodal
dissection in long-term results in gastric resections has been debated
for several decades. Level X lymph nodes are located in the splenic
hilum, and for 20–25% of proximal gastric cancers,
these nodes will have metastatic cancer mandating removal. A randomized
trial showed increased morbidity with a splenectomy and a marginal
improvement in survival. Other tumors of the left upper quadrant
and retroperitoneum may require splenectomy, including large renal
cell carcinomas, left adrenal tumors, and retroperitoneal sarcomas
that may infiltrate upward into the spleen. Although the asplenic
state does make patients susceptible to infections (see earlier
section on Hyposplenism), the spleen should be viewed as an expendable
organ if necessary to accomplish complete resection of malignancies, and
there should be no hesitation to remove the spleen in these situations
to do an appropriate cancer operation.
Carrere N et al: Spleen-preserving distal pancreatectomy
with excision of splenic artery and vein: a case matched comparison with
conventional distal pancreatectomy with splenectomy. World J Surg
Hartgrink HH et al: Extended lymph node dissection for gastric cancer:
who may benefit? Final results of the randomized Dutch gastric cancer
group trial. J Clin Oncol 2004;22:2069.
Pryor A et al: Laparoscopic distal pancreatectomy with splenic
preservation. Surg Endosc 2007;21:2326.
Yu W et al: Randomized clinical trial of splenectomy versus
splenic preservation in patients with proximal gastric cancer. Br
J Surg 2006;93:559.
Splenosis (Splenic Autotransplantation)
In splenosis, multiple small implants of splenic tissue grow
in scattered areas on the peritoneal surfaces throughout the abdomen.
They arise from dissemination and autotransplantation of splenic
fragments following traumatic rupture of the spleen. Splenic implants
or intentional autotransplants are capable of cell culling, and
some immunologic function appears to be exhibited in cases of intentional
autotransplantation. Aggressive attempts at surgical excision are
not warranted. Splenosis is usually an incidental finding discovered
much later during laparotomy for an unrelated problem. However,
the implants stimulate formation of adhesions and may be a cause
of intestinal obstruction. They must be distinguished from peritoneal
nodules of metastatic carcinoma and from accessory spleens. Histologically,
they differ from accessory spleens by the absence of elastic or
smooth muscle fibers in the delicate capsule.
Cothren CC et al: Radiographic characteristics
of postinjury splenic autotransplantation: avoiding a diagnostic
dilemma. J Trauma-Injury Infection & Crit Care 2004;57:537.
Young JT et al: Splenosis: a remote consequence of traumatic
splenectomy. J Am Coll Surg 2004;199:500.