The Spleen
Splenectomy for
Hematologic Disorders
John-Paul Bellistri, MD, and Peter Muscarella II, MD
INDICATIONS FOR SPLENECTOMY
Splenectomy continues to play an important role in the management
of a number of hematologic disorders. Indications for splenectomy
in patients in this population include symptoms related to spleno-
megaly and decreased blood counts related to sequestration or auto-
immune destruction. Symptoms associated with splenomegaly
include abdominal pain, early satiety, weight loss, and abdominal
distension. Cytopenia is defined as a decrease in the circulating cell
count of one or more blood components (anemia, leukopenia,
thrombocytopenia). Hypersplenism is a common complication of
hematologic disorders, whereby the spleen sequesters one or more
blood cell lines. Hypersplenism is defined as cytopenia with a normal
compensatory hematopoietic response by the bone marrow, spleno-
megaly, and correction of cytopenia with splenectomy. In addition,
splenectomy should be considered for patients with unexplained
splenomegaly. Splenectomy for hematologic conditions rarely leads
to cure of the underlying hematologic disorder but may be beneficial
for resolution of hematologic abnormalities and ameliorating symp-
toms of splenomegaly, thus leading to an overall reduction in the
morbidity associated with these disorders. These may be classified
broadly as autoimmune/acquired disorders, congenital disorders,
neoplasms, and myeloproliferative disorders (Box 1).
Autoimmune and Idiopathic Disorders
Immune Thrombocytopenia
Immune thrombocytopenia (ITP; formerly idiopathic/immune
thrombocytopenic purpura) is a condition characterized by platelet
destruction secondary to platelet autoantibodies. This leads to
thrombocytopenia (<100,000/L) with a relative underproduction of
platelets by the bone marrow. Production of immunoglobulin G
(IgG) directed towards platelet glycoproteins (GPIIb/IIIa, GPIb/IX)
increases platelet destruction by the reticuloendothelial system of the
spleen. In addition to humoral immune mediated factors, there is a
component of cellular immunity involved in platelet and megakaryo-
cyte destruction. ITP is a diagnosis of exclusion, and other illnesses
that can cause secondary ITP, such as human immunodeficiency
virus infection, systemic lupus erythematosus, antiphospholipid
antibody syndrome, hepatitis C virus, and lymphoproliferative
disorders, must be considered. Certain drugs also may elicit
similar immune-mediated platelet destruction. A medication
history of cocaine, gold, certain antibiotics, antihypertensives, anti-
inflammatories, heparin, quinidine, and abciximab may result in
this immune phenomenon.
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The prevalence of ITP in adults is about 5 per 100,000 people,
occurring nearly twice as frequently in women as in men. There is
an approximately fourfold increase in prevalence in older adults (>55
years of age). Most patients with ITP have asymptomatic thrombo-
cytopenia. Symptoms of bleeding usually do not occur unless platelet
counts are less than 30,000/mm3. “Platelet-type bleeding” includes
bruising, purpura, petechiae, bleeding from the oral mucosa, epi-
staxis, menorrhagia, and gastrointestinal bleeding. The most severe
complication is intracerebral hemorrhage, and this occurs in approx-
imately 1% of patients. The prevalence of ITP in children is approxi-
mately 12 and 9 per 100,000 in girls and boys, respectively. Children
at a young age (approximately 5 years) may have a sudden onset of
petechiae or purpura, usually days to weeks after an infectious illness.
ITP is commonly self-limited in children, with more than 70% of
patients achieving remission within 6 months of presentation. The
risk of intracerebral hemorrhage in children is less than 0.2%.
Observation is a viable initial treatment option for selected
patients, and this is most successful in the pediatric population when
the platelet count is greater than 20,000/mm3. A trial of observation
is reasonable in adults with platelet counts above 30,000/mm3,
although this is rarely successful. Patients who exhibit persistent
thrombocytopenia despite observation, or who exhibit platelet
counts less than 30,000/mm3 (20,000/mm3 in children), should begin
corticosteroid therapy. The standard initial dose is 1 to 2 mg/kg/day
of prednisone for 2 to 4 weeks followed by a steroid taper. If platelet
counts remain low after 6 to 8 weeks of steroid therapy, or if throm-
bocytopenia recurs after steroid taper, splenectomy should be con-
sidered. Intravenous immunoglobulin (IVIG; 1 mg/kg/day for 1 or 2
days) can be considered for patients who would benefit from a rapid
increase in platelet count (e.g., in the setting of bleeding or in prepa-
ration for an invasive procedure) or for those who are unable to toler-
ate steroids. Careful coordination of IVIG administration with the
referring hematologist is important before surgery because this
usually can be performed as an outpatient.
Splenectomy is indicated for refractory thrombocytopenia,
relapses requiring multiple rounds of therapy, or in patients who
have suffered unwanted side effects. Splenectomy results in a 75% to
85% permanent response with no need for further therapy, and
platelet counts will usually start to increase shortly after surgery. If
perioperative platelet transfusion is required for persistently low
platelet counts or bleeding, transfusion should be withheld until the
splenic artery has been ligated. It has been our experience that sple-
nectomy can be performed safely with minimal bleeding risk, even
in patients with platelet counts below 10,000/mm3.
Thrombotic Thrombocytopenic Purpura
Thrombotic thrombocytopenic purpura (TTP) is a disorder in which
a deficiency of the ADAMS13 protein leads to increased platelet
aggregation and subsequent microvascular thrombosis. The interac-
tion between von Willebrand Factor (vWF) and platelets usually is
controlled by the ADAMS13 protein, which cleaves vWF and pre-
vents platelet aggregation. TTP may occur spontaneously but often
is precipitated by factors such as chemotherapy agents (gemcitabine,
mitomycin C, or calcineurin inhibitors), quinine, cyclosporine,
603
604 Splenectomy for Hematologic Disorders

elevated LDH, low haptoglobin, and indirect hyperbilirubinemia.

BOX 1:  Hematologic Disorders for Which AIHA is classified as warm autoimmune hemolytic anemia (WAIHA)
Splenectomy Can Be Indicated or cold autoimmune hemolytic anemia (CAIHA), based on the
results of a direct agglutinin test (DAT). If the DAT is positive for IgG
I. Autoimmune/acquired disorders alone, or IgG and complement 3d (C3d), then the diagnosis is most
1. Idiopathic thrombocytopenic purpura probably WAIHA. Conversely, if the DAT is positive for C3d alone,
2. Thrombotic thrombocytopenic purpura then CAIHA is the most probable diagnosis.
3. Idiopathic autoimmune hemolytic anemia In WAIHA, polyclonal IgG (sometimes IgA) autoantibodies,
II. Congenital disorders usually directed towards Rh antigens, form a light coat over red blood
Structural abnormalities cells that then are removed by the spleen. The peak incidence of
1. Hereditary spherocytosis WAIHA occurs between the ages of 40 and 70 years, but it can occur
2. Hereditary elliptocytosis at any age. In children, the disease is often self-limited, occurring after
3. Hereditary pyropoikilocytosis a viral infection and resolving over 2 to 3 months. Initial treatment
4. Hereditary stomatocytosis with corticosteroid therapy (prednisone; 1 mg/kg/day) usually results
5. Hereditary xerocytosis in improved hemoglobin levels within several days, and remission
Hemoglobinopathies occurs in 80% of patients. Children generally respond better to
1. Thalassemia steroid therapy than adults. The steroid dose is tapered gradually to
2. Sickle cell anemia the lowest dose needed to control hemolysis. Splenectomy is indi-
Enzymopathies cated for patients who fail to achieve remission by 3 weeks, or for
1. Pyruvate kinase deficiency those in whom hemoglobin levels cannot be maintained with low-
2. Glucose-6-phosphate dehydrogenase deficiency dose steroids. Response rates of 60% to 80% usually are seen within
III. White blood cell neoplasms and myeloproliferative disorders the first 2 weeks after surgery. Approximately 50% of patients will
1. Hodgkin’s lymphoma continue to require low-dose steroids (15 mg/day) to maintain
2. Non-Hodgkin’s lymphoma hemoglobin concentrations after splenectomy.
3. Hairy cell leukemia In CAIHA, monoclonal IgM autoantibodies target red blood cells
4. Chronic lymphocytic leukemia at low temperatures and cause hemolysis. Red blood cell destruction
5. Chronic myelogenous leukemia is complement mediated, and red blood cells are removed by the
6. Primary myelofibrosis liver, rather than the spleen, as seen in WAIHA. CAIHA makes up
IV. Miscellaneous 15% to 25% of AIHA. This disorder usually is caused by an infec-
1. Gaucher’s disease tious process such as Epstein-Barr virus (EBV) infection or by lym-
2. Amyloidosis phoproliferative disorders. Signs and symptoms are usually more
3. Sarcoidosis progressive. Patients also may complain of Raynaud’s phenomenon.
4. Felty’s syndrome Treatment consists of avoiding cold temperatures by staying indoors
and wearing appropriate clothing, which can prevent an acute hemo-
lytic crisis. Alkylating agents such as chlorambucil and cyclophos-
phamide have been used successfully for treatment along with
clopidogrel, ticlopidine, hematopoietic stem cell transplantation, or plasmapheresis. Steroids are usually not an effective treatment. Sple-
pregnancy. nectomy is not indicated for the treatment of this disorder because
The annual incidence of TTP is 4 to 10 cases per million. TTP is the liver is the site of red blood cell destruction and not the spleen.
characterized clinically by a microangiopathic hemolytic anemia If patients require transfusions for supportive care, a blood warmer
(MAHA), severe thrombocytopenia, fever, neurologic complications, is essential. Cross-matching blood products for transfusion can be
and renal failure. Patients often have petechiae (most commonly on challenging for these patients.
the lower extremities), fever, myalgia, and fatigue. Neurologic symp-
toms include headache, mental status changes, seizures, and even
coma. Patients can develop congestive heart failure or cardiac Congenital Diseases of the Blood
arrhythmias. TTP usually is suspected with MAHA and thrombocy-
topenia in the setting of elevated lactate dehydrogenase (LDH), ele- Hereditary Spherocytosis
vated bilirubin, a negative Coombs test, and a peripheral blood smear Hereditary spherocytosis (HS) is characterized by the presence of
demonstrating schistocytes, nucleated red blood cells, and basophilic spherocytes on peripheral blood smear, hemolytic anemia, and
stippling. increased red blood cell clearance by the spleen. HS is the most
Initial therapy consists of daily plasma exchange. Plasmapheresis common congenital anemia, prompting splenectomy with a preva-
is carried out with a goal of exchanging about 1 to 1.5 plasma lence of 1 in 5000 people in Europe and North America. The
volumes. Approximately 70% of patients will respond to this therapy. disorder is also common in Japanese and African populations. HS
Platelet transfusions generally are not recommended for use in TTP represents a heterogeneous group of membrane protein deficiencies
because of the risk of severe clinical deterioration that has been with a common pathophysiology. Most protein defects exhibit
reported after their administration. Rituximab (anti-CD20 antibody) autosomal dominant inheritance (spectrin, ankyrin, band 3 protein).
and glucocorticoids are second-line therapies. Until the 1970s, sple- However, some less common variants are inherited through an
nectomy was the only modality available for the treatment of TTP. autosomal recessive pattern (protein 4.2). Membrane protein muta-
Currently, splenectomy generally is reserved for refractory thrombo- tions lead to destabilization of the lipid bilayer with subsequent
cytopenia or frequent relapses. When combined with high-dose release of lipids from the membrane surface. The consequent
steroid therapy, splenectomy has been shown to improve disease-free decrease in cell membrane surface area results in sphering of the
interval. The response rate for splenectomy for TTP is 40%, consider- red blood cell with decreased deformability, impaired passage of
ably lower than that seen for ITP. the red blood cell through the splenic pulp, and increased osmotic
fragility. The spherocytes then are destroyed prematurely within
Autoimmune Hemolytic Anemia the spleen.
Autoimmune hemolytic anemia (AIHA) is a disorder in which auto- HS may manifest as mild or severe forms. In mild forms, patients
antibodies are formed and directed against red blood cell antigens. may be asymptomatic or suffer only mild jaundice. Patients with
AIHA should be suspected in patients with anemia, reticulocytosis, more severe forms may have anemia, jaundice, splenomegaly, and

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cholelithiasis with pigmented (bilirubin) gallstones. Peripheral blood
smear demonstrates spherocytes and reticulocytes. Treatment by
splenectomy is curative for almost all patients with dominant
forms of spherocytosis and is indicated in the presence of growth
retardation, skeletal changes, symptomatic hemolytic disease,
anemia-induced organ dysfunction, leg ulcers, or development of
extramedullary hematopoietic tumors. There is some controversy
over whether patients with mild or moderate forms of HS who do
not exhibit these sequelae should undergo splenectomy. Preoperative
abdominal ultrasonography should be performed for patients under-
going surgery for HS, and cholecystectomy should be performed at
the time of splenectomy for patients with gallstones. Splenectomy
usually is delayed until after age 5 to decrease the risk of overwhelm-
ing post-splenectomy infection (OPSI). There may be a role for
partial splenectomy in children younger than 5 years because some
studies have shown an improvement in anemia with potential main-
tenance of splenic immune function in this group.
Hereditary Elliptocytosis
Hereditary elliptocytosis (HE) is a rare disorder that results from
mutation of the red blood cell membrane skeleton proteins spectrin,
protein 4.1R, and glycophorin C. HE has a prevalence of approxi-
mately 3 to 5 per 10,000 in the United States. Inheritance usually
follows an autosomal dominant pattern, and the disorder is more
common in people of African and Mediterranean descent. The true
incidence is unknown because of the wide variety of clinical pre-
sentations. Most patients with the dominant inheritance are asymp-
tomatic with a mild compensated anemia or no anemia at all.
Affected cells are morphologically characterized by biconcave ellip-
tocytes, or rod-shaped, cells. These cells are much more deformable
than spherocytes, and patients have a less severe clinical course. In
contrast, the rare autosomal recessive form can lead to severe hemo-
lysis. Patients with mild HE, who are asymptomatic and without
evidence of hemolysis, do not require treatment. Patients with
chronic hemolysis may require blood transfusions and daily folic
acid. Splenectomy is indicated for patients with symptomatic anemia
and is curative.
Hereditary Pyropoikilocytosis
Hereditary pyropoikilocytosis (HPP) is an autosomal recessive,
severe hereditary hemolytic anemia in which red blood cells demon-
strate striking micropoikilocytosis and thermal instability. HPP rep-
resents a subtype of HE, arising from the same molecular defects.
Patients with HPP usually have a common hereditary elliptocytosis
mutation from one parent and a milder subclinical defect in spectrin
synthesis from the other parent. The disease usually is seen as anemia
and jaundice in newborns and infants. Splenectomy is curative for
patients with severe anemia.
Hereditary Stomatocytosis (Hydrocytosis) and
Xerocytosis (Desiccytosis)
Hereditary stomatocytosis and xerocytosis are rare autosomal domi-
nant hemolytic anemias characterized by a variable clinical course
from asymptomatic to mild hemolytic anemia. In stomatocytosis, the
underlying defect leads to increased erythrocyte cation permeability
and an increased erythrocyte volume. In xerocytosis, there is a
decrease in intracellular cation content and cell volume. Stomato-
cytes have a mouth-shaped area of central pallor, whereas target cells
and spiculated cells are identified on peripheral blood smear in
patients with xerocytosis. For cases of severe hemolysis, splenectomy
may improve the anemia but does not fully correct the hemolysis. In
patients with these conditions, the role for splenectomy should be
considered carefully. Patients with stomatocytosis and xerocytosis
can develop severe complications after splenectomy, such as hyper-
coagulability leading to catastrophic thrombotic episodes and chronic
pulmonary hypertension. Fortunately, most patients with these rare
forms of hemolytic anemia have a mild clinical course and do not
require splenectomy.
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Th e S p l e e n 605
Thalassemia
The thalassemias are a group of autosomally dominant inherited
hematologic disorders caused by a defect in the synthesis of one or
more of the hemoglobin chains. As a group, the thalassemias repre-
sent the most common genetic disorder known worldwide. The
clinical manifestations associated with thalassemia arise from quan-
titatively imbalanced accumulation of globin subunits and inade-
quate hemoglobin production. Each subtype is characterized by the
affected globin chain (alpha, beta, gamma, or delta). The beta subtype
is the most common form of thalassemia in the United States and
occurs mainly in patients of Italian and Greek descent.
Patients that have the heterozygous (thalassemia minor) form of
beta-thalassemia are usually asymptomatic with a microcytosis and
mild anemia. The homozygous form (thalassemia major or Cooley’s
anemia) is much more severe. Patients are usually asymptomatic
until 6 months of age because of the presence of fetal hemoglobin
(HgF). Patients then have severe hemolytic anemia, abdominal swell-
ing, growth retardation, irritability, jaundice, pallor, splenomegaly,
pigmented gallstones, and skeletal abnormalities. Laboratory values
show a severe microcytic anemia with nucleated red blood cells,
anisocytosis, and poikilocytosis. Patients also may have mild neutro-
penia and thrombocytopenia.
Treatment consists of periodic, lifelong blood transfusion and
iron chelation therapy. Splenectomy is reserved for patients with
increased blood transfusion requirements arising in the setting of
hypersplenism. Massive splenomegaly is usually rare in appropriately
transfused patients, and by itself, is not an indication for splenec-
tomy. A transfusion requirement of more than 180 to 200 mL/kg/
year of packed red blood cells usually represents excessive red blood
cell requirements and warrants splenectomy. A 25% to 60% reduc-
tion in transfusion requirements can be expected after splenectomy.
Splenectomy usually is delayed until the age 4 or 5 to decrease the
risk of infectious complications (OPSI).
Sickle Cell Anemia
Sickle cell anemia is an autosomal recessive hemoglobinopathy char-
acterized by an amino acid substitution on the beta chain of the
hemoglobin molecule. The abnormal hemoglobin S (HgS) molecule
confers red blood cells with the propensity to deform and take on a
sickle shape when exposed to low oxygen tension. Sickle cells cause
stasis and vasoocclusion in the microvasculature of the body, leading
to tissue ischemia, severe pain, and chronic organ tissue damage.
Exacerbations of symptoms are referred to as sickle cell crises. Patients
who are homozygous for the disorder have sickle cell disease, and
many undergo autosplenectomy by an early age as a result of multiple
infarcts. Treatment is by avoidance of situations that can precipitate
a sickle cell crisis, hydration, and transfusions.
Splenectomy rarely is indicated for sickle cell disease because of
autoinfarction of the spleen but can be indicated for splenic abscesses
and splenic sequestration. Splenic abscess can be a complication of
splenic infarction and is an indication for splenectomy. Acute splenic
sequestration has a high mortality (up to 15%). It is characterized by
massive splenomegaly, acute exacerbation of anemia, and hypovole-
mia. This initially is treated with restoration of blood volume and
red blood cell mass, but recurrence is common. Splenectomy should
be considered to prevent further episodes of sequestration. It is
important to maintain euvolemia and normothermia to prevent
complications of an acute sickle cell crisis in the perioperative period.
Pyruvate Kinase Deficiency
Pyruvate kinase deficiency (PKD) is the most common genetic defect
causing congenital nonspherocytic hemolytic anemia. PKD is an
autosomal recessive disease that occurs when a defect in the glycolytic
pathway results in a deficiency of adenosine triphosphate. Red blood
cells are less deformable and often are destroyed in the spleen, leading
to splenomegaly. Hemolysis can be exacerbated by acute infections
and pregnancy. Patients with PKD have mild to severe anemia
606 Splenectomy for Hematologic Disorders
accompanied by splenomegaly. Clinically, the effects of hemolysis are
often milder than in other hemolytic anemias because of elevated
levels of 2,3-DPG in pyruvate kinase deficient red cells. These red
blood cells permit more efficient delivery of oxygen to the tissues
given the same concentration of hemoglobin in the blood. Splenec-
tomy is indicated for patients with the severe hemolytic variants of
PKD, or patients that require significant numbers of transfusions. As
in the previous sections, splenectomy commonly is delayed until after
the age of 5.
G6PD Deficiency
Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most
common enzyme deficiency in the world. The disease is an X-linked
disorder of the enzyme G6PD in the glutathione pathway that leads
to damage of red cell macromolecules by toxic oxygen products.
Hemolysis can be precipitated by acute infections, oxidant drugs
(sulfas and antimalarials), and fava beans. Treatment is directed at
inciting agent. Severe anemia is treated with transfusion. Splenec-
tomy is rarely, if ever, indicated for the anemia associated with G6PD
deficiency.
Neoplasms and Myeloproliferative Disorders
Hodgkin’s Lymphoma
Hodgkin’s lymphoma is a malignant neoplasm of lymphoreticular
cell origin that usually affects young adults in their second and third
decades. Primary treatment may consist of chemotherapy and/or
radiation. Historically, splenectomy was performed as part of a
staging laparotomy that included lymph node sampling and liver
biopsy. Staging laparotomy is used rarely today and largely has been
replaced by imaging modalities such as computerized tomography
(CT) scanning and positron emission tomography scanning. Sple-
nectomy rarely is indicated but may be beneficial for patients who
develop thrombocytopenia or symptoms related to splenomegaly.
Non-Hodgkin’s Lymphoma
Non-Hodgkin’s lymphoma (NHL) is the most common type of lym-
phoma and comprises a diverse group of lymphomas varying in
prognosis based on histologic subtype and clinical features. NHL
represents the most common primary splenic neoplasm with splenic
involvement occurring in 65% to 80% of cases. Splenectomy is indi-
cated for symptoms related to massive splenomegaly and cytopenias
resulting from splenic sequestration. It is not uncommon for hema-
tologists to request splenectomy to assist with diagnosis to determine
appropriate therapy. This may occur in situations in which patients
have failed to respond to therapy or when inadequate tissue is avail-
able for proper histologic or cytometric analysis.
There are some subtypes of NHL that involve the spleen more
than others. Splenic marginal zone lymphoma (SMZL) is an indolent
B-cell lymphoma causing microvascular invasion of the spleen with
marginal zone differentiation that occurs in older patients. Splenec-
tomy is both diagnostic and therapeutic in SMZL. Splenectomy is an
appropriate initial treatment and has been shown to lead to partial
or complete remission in many patients because the spleen is the site
of lymphoma origin. Chemotherapy may be recommended for some
patients as the initial therapy at the discretion of the referring oncol-
ogist, and data suggest that this is appropriate.
Hairy Cell Leukemia
Hairy cell leukemia (HCL) is a rare leukemia, representing 2% of
leukemias. Patients have fatigue, left upper quadrant abdominal pain,
fever, infection, and/or coagulopathy. The disease is characterized by
B-lymphocytes that possess cytoplasmic projections from the cell
membrane (“hairy cells”). This is an indolent disease that commonly
occurs in the fifth decade with splenomegaly (80% to 90% of
patients), pancytopenia, neoplastic peripheral mononuclear cells,
and bone marrow infiltration. Pancytopenia is caused by hypersplen-
ism and replacement of bone marrow by leukemic cells.
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In the past, splenectomy was an essential component of standard
of treatment. Splenectomy results in symptomatic improvement
from massive splenomegaly and a 40% to 70% improvement in the
hematologic cell lines for up to 10 years irrespective of splenic size.
Treatment with the purine analogues pentostatin and cladribine has
supplanted the use of interferon-alpha2, other chemotherapeutic
agents, and splenectomy as primary therapy. These agents have
proven response rates of 92%, with complete remission rates of 80%
and 10-year survival rates greater than 90%. Splenectomy rarely is
indicated for the treatment of HCL and is reserved for cases of
incomplete response to first-line therapy, persistent splenomegaly in
the absence of bone marrow involvement, atraumatic splenic rupture,
and severe bleeding from thrombocytopenia.
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) represents a B-cell leukemia in
which there is progressive accumulation of functionally incompetent
lymphocytes. CLL arises usually after the fifth decade of life and is
more common in men than in women. Splenic infiltration is common
in advanced stages and can lead to severe splenomegaly and substan-
tial cytopenias because of hypersplenism. Splenectomy is indicated
to relieve symptoms associated with massive splenomegaly, such as
abdominal pain, distension, and early satiety. Splenectomy for the
treatment of severe thrombocytopenia and anemia, in the setting of
secondary ITP or AIHA, has a 60% to 70% hematologic response rate
and has been shown to lead to improved overall survival.
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) is a disorder of abnormal
proliferation and accumulation of granulocytes. Ninety-five percent
of CML patients will have the characteristic Philadelphia chromo-
some with a reciprocal translocation between chromosomes 9 and
22 [t(9;22)] leading to fusion of the breakpoint cluster region and
Abelson leukemia virus gene. CML may occur in childhood but is
found mainly in adults with a mean age of 65 at diagnosis. Diagnosis
commonly is made during the chronic phase, which is commonly
asymptomatic. Splenomegaly occurs in 40% of patients in the chronic
phase. The disease can progress to an accelerated phase with the
development of fever, night sweats, weight loss, bone pain, increased
white blood cell count, and increasing splenomegaly despite medical
therapy. An acute blastic crisis can develop, resulting in severe sple-
nomegaly and hypersplenism, leading to severe anemia, bleeding
complications, and infection. Current first-line therapy is with ima-
tinib, a tyrosine kinase inhibitor. Bone marrow transplantation or
interferon-alpha can be used in cases of poor response or relapse.
Splenectomy has not shown any survival benefit in the early chronic
phase or before bone marrow transplantation but may offer pallia-
tion in patients with severe symptoms of splenomegaly or hemato-
logic disorders from hypersplenism.
Primary Myelofibrosis (Myelofibrosis
With Myeloid Metaplasia)
Primary myelofibrosis (PMF) is a chronic malignant hematologic
disorder that results in hyperplasia of abnormal myeloid precursor
cells leading to marrow fibrosis and extramedullary hematopoiesis in
the liver and spleen. This can lead to significant splenomegaly, cyto-
penias from splenic sequestration, and portal hypertension from
venous thrombosis. PMF is prevalent in patients with history of
radiation or toxic industrial agent exposure. It is more common in
men than women with the average age of diagnosis being 65 years.
Splenectomy is indicated for patients who develop hemolysis
requiring significant transfusions, thrombocytopenia, symptomatic
splenomegaly, recurrent splenic infarctions, hypercatabolic symp-
toms (anorexia, fatigue, fever, night sweats, weight loss) and portal
hypertension with refractory ascites and variceal hemorrhage. Sple-
nectomy in PML has a substantial risk of morbidity (15% to 30%)
and mortality (10%) and only should be performed in a select
group of patients. Splenectomy in patients with PML has been

associated with hemorrhage, infection, leukocytosis, severe throm-
bocytosis (18% to 50%), progressive hepatomegaly (12% to 29%),
fatal hepatic failure (7%), and leukemic transformation (11% to
20%). Some studies have reported an increase in the complication
rate with a laparoscopic approach versus open in PMF. The appro-
priate use of palliative splenectomy in PMF can result in improved
quality of life for patients that are unresponsive to less invasive
approaches. Postoperative use of platelet-lowering agents such as
hydroxyurea, interferon-alpha, aspirin, and anagrelide has been
shown to aid in reduction of thrombotic complications. Surgical
technique involving ligation of the splenic vein flush at its conflu-
ence with the superior mesenteric vein has been described to improve
laminar flow and decrease portal vein thrombosis. Compensatory
massive hepatic enlargement can be treated with low-level radiation
and chemotherapy.
Miscellaneous Disorders
Amyloidosis
Amyloidosis is a common disorder that results in extracellular depo-
sition of insoluble fibrillar proteins in tissues and organs. Hepato-
splenomegaly may occur in 25% of patients, and severe splenomegaly
is seen in approximately 10% of individuals. These patients may
develop functional splenic insufficiency. Splenectomy is indicated for
signs and symptoms associated with a massively enlarged spleen. This
does not, however, alter the ultimate course of the disease. In addi-
tion, patients with severe hepatic dysfunction from amyloid deposi-
tion may develop coagulopathy associated with factor X deficiency.
In these patients, splenectomy may improve factor X levels. Periop-
erative administration of factor VIIa is important to control bleeding
in patients undergoing splenectomy.
Gaucher’s Disease
Gaucher’s disease is a glycolipid storage disease in which a deficiency
in beta-glucosidase (glucocerebrosidase) leads to deposition of glu-
cocerebroside in the reticuloendothelial system. This deposition leads
to severe organomegaly, pulmonary infiltrates, and bone marrow
infiltration. Patients can have anemia, thrombocytopenia, osteope-
nia, bone pain, osteonecrosis, and massive hepatosplenomegaly. Sple-
nectomy is indicated for severe and symptomatic splenomegaly and
refractory cytopenia. Partial splenectomy has been advocated in some
children with Gaucher’s disease to preserve some splenic function.
Splenectomy does not alter disease progression but can improve
thrombocytopenia and reduce the risk of splenic rupture. Because
the spleen is a reservoir for storage material, splenectomy for Gau-
cher’s disease can result in redistribution and deposition in other
organs resulting in severe bone disease (tenfold increased risk of
osteonecrosis) and worsening lung or kidney function. Therefore
careful patient selection is recommended before splenectomy in this
patient population.
Felty’s Syndrome
Felty’s syndrome comprises rheumatoid arthritis, otherwise unex-
plained neutropenia, and splenomegaly. The size of the spleen may
be variable, and splenomegaly is not essential for the diagnosis. The
HLA DR4 antigen will be present in 85% of cases. Patients have severe
or chronic infections as a result of the neutropenia, especially with
neutrophil counts below 0.5 × 109/mm3. Patients may have spontane-
ous remissions of their neutropenia. First-line treatment consists of
low-dose methotrexate or disease-modifying antirheumatic drugs.
Granulocyte colony-stimulating factor may be used for treatment
failures, in cases of increased infection risk, or before planned joint
surgery. Splenectomy is indicated when medical treatment has failed
as manifested by recurrent infections or severe neutropenia. Splenec-
tomy results in an 80% hematologic response rate. Unfortunately,
infectious complications associated with Felty’s syndrome may still
ensue, and these do not always correlate with improvements in gran-
ulocyte counts.
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Th e S p l e e n 607
Sarcoidosis
Sarcoidosis is a noncaseating granulomatous disease. Although 90%
of patients have primary lung involvement, the disease can affect
every organ in the body. Primary splenic sarcoid is very rare, and
splenic involvement is often found as part of a multiorgan sarcoid-
osis. Up to 40% of patients with sarcoidosis have splenomegaly and
3% have massive splenomegaly. Splenic involvement occurs in 10%
to 15% of patients with sarcoidosis. Treatment is primarily medical
and generally includes corticosteroids or methotrexate. Indications
for splenectomy include symptoms related to symptoms of spleno-
megaly, intractable pain, exclusion of a neoplastic process, and hyper-
splenism. Splenectomy does not alter the course of sarcoidosis but
has been shown to aid in the treatment of refractory hypercalcemia
in some case reports.
Idiopathic Splenomegaly
In the setting of splenomegaly without a clear cause, splenectomy has
a diagnostic and therapeutic role. Historical series have revealed a
40% to 70% occurrence of lymphoma in this patient population.
Most of these patients do not exhibit any clinical signs of lymphade-
nopathy to otherwise indicate malignancy. Tissue obtained through
splenectomy may be the only means of performing the appropriate
histopathologic or cytologic analyses to make a diagnosis. When
hypersplenism is present, splenectomy can alleviate symptoms of
splenomegaly and correct cytopenias. Early diagnosis of lymphoma
can improve survival in this patient population because it provides
the opportunity for early diagnosis and treatment.
PREOPERATIVE CONSIDERATIONS
Preoperative imaging is important for operative planning. Both CT
and ultrasound are options for assessing splenic size. CT provides the
advantage of providing information regarding anatomic relation-
ships, vascular anatomy, presence of accessory spleens (Figure 1),
perisplenic lymphadenopathy, and inflammation. Splenic artery
embolization may be advantageous to prevent excessive blood loss in
the setting of severe thrombocytopenia, or in patients who do not
wish to receive blood transfusions for religious reasons. In addition,
embolization may help to reduce the size of the spleen in cases of
massive splenomegaly (Figure 2) to allow for laparoscopic resection.
Patient selection is important in these cases because embolization
may cause severe pain and ischemic complications.
Appropriate perioperative antibiotics are given within 60 minutes
before making skin incision and should cover skin flora. Low-
molecular-weight heparin should be administered subcutaneously
FIGURE 1  Accessory spleen.
608 Splenectomy for Hematologic Disorders
FIGURE 2  Massive splenomegaly in a patient who underwent
splenectomy for complications of a lymphoproliferative disorder.
before induction of anesthesia and should be continued postopera-
tively for up to 1 month as prophylaxis for splanchnic thrombosis.
The use of an orogastric or nasogastric tube can reduce gastric dis-
tension and can improve visualization and dissection of the short
gastric vessels along the greater curvature of the stomach. Blood
products should be available intraoperatively, especially in patients
with severe thrombocytopenia. Platelets are transfused only as
needed after ligation of the splenic artery. If patients have been
treated with chronic corticosteroids, stress dose steroids should be
administered with a rapid taper postoperatively. In elective cases, it
is recommended to vaccinate patients against encapsulated organ-
isms (Haemophilus influenzae B, polyvalent Pneumococcus, and
Meningococcus vaccines) 2 weeks before splenectomy. If splenectomy
is emergent, the patient should be vaccinated postoperatively.
SURGICAL PROCEDURE
Laparoscopic splenectomy has become the standard approach for
performing splenectomy in patients with hematologic disorders.
Laparoscopic splenectomy provides the advantages of shorter length
of stay, decreased postoperative pain, and decreased morbidity.
Recent studies have shown a trend toward shorter operative times
that are comparable to open splenectomy in cases of normal or
moderately enlarged spleens. Most data show comparable detection
of accessory spleens that can result in disease recurrence in cases of
autoimmune hematologic disorders. Much of the controversy sur-
rounding laparoscopic splenectomy involves the size of the spleen.
The normal adult spleen measures up to 11 cm in length and weighs
approximately 80 to 300 g. Moderate splenomegaly generally is
defined as a spleen that is 11 to 20 cm in greatest dimension, and
massive splenomegaly represents a spleen that is more than 20 cm in
greatest dimension. Laparoscopic splenectomy can be performed
safely in patients with splenomegaly, even in cases in which the spleen
is more than 20 cm in length. It has been our experience that the
ability to perform laparoscopic splenectomy in cases of massive sple-
nomegaly often is limited only by the size of the retrieval device.
Regardless, the surgeon should exercise good judgment in patient
selection for laparoscopic splenectomy. Factors to be considered
should include medical comorbidities, splenic size, indication for
surgery, blood counts, coexisting coagulopathy, and history of previ-
ous splenic irradiation. The hand-assisted laparoscopic approach
may be useful for selected patients with splenomegaly and allows
for rapid control of hilar blood flow and assistance with retraction.
Nevertheless, open surgery should never be considered to be a failure
and actually may be the safest approach for some patients.
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FIGURE 3  Port placement.
For laparoscopic splenectomy, the patient may be placed in a
lateral decubitus position or supine with a bump under the left side.
A bean bag can be used to facilitate positioning for surgeons who
prefer the left lateral decubitus position. A split-leg bed can be helpful
when the patient is supine and allows the primary operating surgeon
to stand between the legs during the dissection. Port placement gen-
erally includes a 12-mm periumbilical camera port, a 5-mm right
upper quadrant port, a 5-mm left upper quadrant port, and a 12-mm
left sided port placed more inferiorly and laterally to allow for passage
of the endoscopic stapling device (Figure 3). Access to the abdomen
can be gained using a Veress needle, an optical trocar, or an open
approach depending on the preference of the surgeon. The patient
generally is repositioned in reverse Trendelenburg position with the
left side up, after port placement and camera insertion, to facilitate
exposure of the spleen. For patients with a generous liver or spleno-
megaly, the use of a self-retaining liver retractor, such as the Nathan-
son device with a Fast-clamp, can facilitate visualization. This
generally is placed through a 5-mm incision created at the groove
between the xiphoid process and the left costal margin. The abdomen
is explored, paying careful attention to identify any accessory spleens
that may be present. The liver also should be inspected for signs of
cirrhosis. The splenocolic ligament is mobilized and divided with an
energy device. This allows for further mobilization and inferior
retraction of the splenic flexure of the colon. The gastrosplenic liga-
ment and the short gastric vessels then are divided using an ultra-
sonic vibrational energy device, endoscopic metallic clips, or bipolar
energy device. This dissection should be carried up the level of the
left crus, and the stomach can be retracted to the right. The spleno-
renal ligament then is dissected to identify the splenic artery and
splenic vein within the splenic hilum (Figure 4). These structures
then are divided using a vascular load on an endoscopic linear sta-
pling device. The splenophrenic ligament is divided last because this
structure maintains cephalad/lateral retraction of spleen during divi-
sion of the hilar vessels.
The spleen then is placed into an endoscopic bag. The edges of
the bag then are brought through the lateral trocar site. The spleen
is morcellated using ringed forceps and extracted in a piecemeal
fashion. After extraction, the splenic bed, hilum, and greater

FIGURE 4  Laparoscopic view of splenic hilar vessels.
curvature of the stomach should be inspected thoroughly to ensure
hemostasis. At this point the abdomen should be examined again for
splenunculi or accessory spleens. The most common locations for
splenunculi are the gastrosplenic ligament and greater omentum. For
open splenectomy, a midline or left subcostal incision may be used.
The midline incision may be preferable in patients with massive
splenomegaly or a narrow costal margin.
POSTOPERATIVE MANAGEMENT AND
COMPLICATIONS
Patients should be monitored for hemorrhage, atelectasis, and infec-
tion in the early postoperative period. The most common site of
hemorrhage at re-exploration is from the undersurface of the dia-
phragm. Infectious complications include subphrenic abscess and
OPSI. If patients were unable to receive preoperative vaccinations,
they should be administered 2 weeks after surgery. If compliance is
a concern, they may be administered before discharge from the hos-
pital. Vaccinations should be held for 3 months after surgery in
patients who have been treated with immunosuppressive agents.
Patients should receive booster vaccinations every 5 years for pneu-
mococcus and meningococcus. Prophylactic antibiotics have been
recommended for at least 2 years in children but generally are not
used in adults. Penicillin is the agent of choice (Box 2). In patients
with penicillin allergies, trimethoprim-sulfamethoxazole or erythro-
mycin may be used.
The risk for OPSI is highest in children under the age of 5 and
within the first 2 years after surgery but does carry a lifelong risk.
Risk factors for OPSI include age (14% in children younger than 5
years of age vs 0.5% in children older than 5 years of age), splenec-
tomy for a hematologic disorder, and history of immunosuppressant
therapy. OPSI has a reported fatality rate of 50%. Streptococcus pneu-
moniae, Neisseria meningitides, Haemophilus influenza type B, and
group A Streptococcus account for most of the severe infections. Esch-
erichia coli, Capnocytophaga species, and intraerythrocytic parasites
also pose a risk. Patients typically have an upper respiratory infection
that rapidly proceeds to sepsis and multisystem organ failure. A high
index of suspicion is required, and early and aggressive treatment
with broad-spectrum antibiotics and supportive measures can be
lifesaving.
Other postoperative complications include a thrombocytosis,
leukocytosis, pneumonia, pleural effusion, pancreatitis, pancreatic
fistula, venous thrombosis, injury to adjacent organs, and hyper-
splenism resulting from the presence of a missed accessory spleen.
Risk factors for postoperative complications include massive spleno-
megaly and myeloproliferative disorders (mainly PMF). Thrombo-
cytosis can occur immediately postoperatively and peaks at 3 weeks.
Antiplatelet therapy is indicated with thrombotic complications or
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Th e S p l e e n 609
BOX 2:  Guidelines for Overwhelming
Post-Splenectomy Infection Prophylaxis
Incidence of OPSI
First 2 years after splenectomy: adults (0.9%) children (5.0%)
Risk factors: Age <5, hematologic disorders, immunosuppression
Vaccination and OPSI Prophylaxis Recommendations
Vaccinations
H. influenza B, Pneumococcus, Meningococcus 2 weeks
preoperatively (elective cases) or at discharge or 2 weeks
postoperatively
If patient received immunosuppression therapy, vaccinate 3
months after treatment
Booster vaccinations for Pneumococcus +/− Meningococcus every
5 years
H. influenza Ab titers can be followed for need of a booster dose
Consider monitoring Ab titers of all three in
immunocompromised patients
Antibiotic Prophylaxis
• Less than 60 minutes before incision to cover skin flora
• Continue prophylactic antibiotics for 2 years postoperatively
in children (age <16)
• Lifelong prophylaxis if immunocompromised
OPSI, Overwhelming post-splenectomy infection prophylaxis.
prophylactically when platelet levels reach 1 million. Patients with an
accessory spleen will have an absence of Howell-Jolly, Heinz bodies,
and target cells and may require re-exploration for accessory spleens
or selective embolization.
Portal vein or mesenteric vein thrombosis can be a serious
complication of splenectomy. Post-splenectomy splanchnic venous
thrombosis has been reported in 20% to 50% of patients under-
going splenectomy, with higher rate for laparoscopic splenectomy.
For this reason, patients can be maintained on prophylactic doses
of low-molecular-weight heparin for 4 weeks postoperatively. Risk
factors for thrombosis include myeloproliferative disorders, hemo-
lytic anemias, a long splenic vein stump, postoperative thrombo-
cytosis, hypercoagulable state, and splenomegaly. Patients have
vague abdominal pain, distension, ileus, fever, and nausea and
can develop intestinal infarction and portal hypertension. In the
setting of splanchnic venous thrombosis, systemic anticoagulation
is required with recannulation rates of more than 90% when
treated promptly.
CONCLUSION
Splenectomy remains an important tool for the treatment of a wide
range of acquired, congenital, and neoplastic hematologic disorders.
Splenectomy also can serve as a diagnostic tool in the setting of
idiopathic splenomegaly. Management of patients undergoing sple-
nectomy requires careful preoperative preparation and postoperative
management to ensure a safe perioperative course.
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Feldman LS, Demyttenaere SV, Polyhhronopoulos GN, et al. Refining the
selection criteria for laparoscopic versus open splenectomy for spleno-
megaly. J Laparoendosc Adv Surg Tech A. 2008;18:13-19.
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the clinical practice guidelines of the European Association for Endo-
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Ikeda M, Sekimoto M, Takiguchi S, et al. High incidence of thrombosis of
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