Splenectomy For Hematologic Disorders
Splenectomy For Hematologic Disorders
Splenectomy for 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
Hematologic Disorders 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
John-Paul Bellistri, MD, and Peter Muscarella II, MD 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-
INDICATIONS FOR SPLENECTOMY 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
Splenectomy continues to play an important role in the management at a young age (approximately 5 years) may have a sudden onset of
of a number of hematologic disorders. Indications for splenectomy petechiae or purpura, usually days to weeks after an infectious illness.
in patients in this population include symptoms related to spleno- ITP is commonly self-limited in children, with more than 70% of
megaly and decreased blood counts related to sequestration or auto- patients achieving remission within 6 months of presentation. The
immune destruction. Symptoms associated with splenomegaly risk of intracerebral hemorrhage in children is less than 0.2%.
include abdominal pain, early satiety, weight loss, and abdominal Observation is a viable initial treatment option for selected
distension. Cytopenia is defined as a decrease in the circulating cell patients, and this is most successful in the pediatric population when
count of one or more blood components (anemia, leukopenia, the platelet count is greater than 20,000/mm3. A trial of observation
thrombocytopenia). Hypersplenism is a common complication of is reasonable in adults with platelet counts above 30,000/mm3,
hematologic disorders, whereby the spleen sequesters one or more although this is rarely successful. Patients who exhibit persistent
blood cell lines. Hypersplenism is defined as cytopenia with a normal thrombocytopenia despite observation, or who exhibit platelet
compensatory hematopoietic response by the bone marrow, spleno- counts less than 30,000/mm3 (20,000/mm3 in children), should begin
megaly, and correction of cytopenia with splenectomy. In addition, corticosteroid therapy. The standard initial dose is 1 to 2 mg/kg/day
splenectomy should be considered for patients with unexplained of prednisone for 2 to 4 weeks followed by a steroid taper. If platelet
splenomegaly. Splenectomy for hematologic conditions rarely leads counts remain low after 6 to 8 weeks of steroid therapy, or if throm-
to cure of the underlying hematologic disorder but may be beneficial bocytopenia recurs after steroid taper, splenectomy should be con-
for resolution of hematologic abnormalities and ameliorating symp- sidered. Intravenous immunoglobulin (IVIG; 1 mg/kg/day for 1 or 2
toms of splenomegaly, thus leading to an overall reduction in the days) can be considered for patients who would benefit from a rapid
morbidity associated with these disorders. These may be classified increase in platelet count (e.g., in the setting of bleeding or in prepa-
broadly as autoimmune/acquired disorders, congenital disorders, ration for an invasive procedure) or for those who are unable to toler-
neoplasms, and myeloproliferative disorders (Box 1). ate steroids. Careful coordination of IVIG administration with the
referring hematologist is important before surgery because this
Autoimmune and Idiopathic Disorders usually can be performed as an outpatient.
Splenectomy is indicated for refractory thrombocytopenia,
Immune Thrombocytopenia relapses requiring multiple rounds of therapy, or in patients who
Immune thrombocytopenia (ITP; formerly idiopathic/immune have suffered unwanted side effects. Splenectomy results in a 75% to
thrombocytopenic purpura) is a condition characterized by platelet 85% permanent response with no need for further therapy, and
destruction secondary to platelet autoantibodies. This leads to platelet counts will usually start to increase shortly after surgery. If
thrombocytopenia (<100,000/L) with a relative underproduction of perioperative platelet transfusion is required for persistently low
platelets by the bone marrow. Production of immunoglobulin G platelet counts or bleeding, transfusion should be withheld until the
(IgG) directed towards platelet glycoproteins (GPIIb/IIIa, GPIb/IX) splenic artery has been ligated. It has been our experience that sple-
increases platelet destruction by the reticuloendothelial system of the nectomy can be performed safely with minimal bleeding risk, even
spleen. In addition to humoral immune mediated factors, there is a in patients with platelet counts below 10,000/mm3.
component of cellular immunity involved in platelet and megakaryo-
cyte destruction. ITP is a diagnosis of exclusion, and other illnesses Thrombotic Thrombocytopenic Purpura
that can cause secondary ITP, such as human immunodeficiency Thrombotic thrombocytopenic purpura (TTP) is a disorder in which
virus infection, systemic lupus erythematosus, antiphospholipid a deficiency of the ADAMS13 protein leads to increased platelet
antibody syndrome, hepatitis C virus, and lymphoproliferative aggregation and subsequent microvascular thrombosis. The interac-
disorders, must be considered. Certain drugs also may elicit tion between von Willebrand Factor (vWF) and platelets usually is
similar immune-mediated platelet destruction. A medication controlled by the ADAMS13 protein, which cleaves vWF and pre-
history of cocaine, gold, certain antibiotics, antihypertensives, anti- vents platelet aggregation. TTP may occur spontaneously but often
inflammatories, heparin, quinidine, and abciximab may result in is precipitated by factors such as chemotherapy agents (gemcitabine,
this immune phenomenon. mitomycin C, or calcineurin inhibitors), quinine, cyclosporine,
603
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
604 Splenectomy for Hematologic Disorders
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Th e S p l e e n 605
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
606 Splenectomy for Hematologic Disorders
accompanied by splenomegaly. Clinically, the effects of hemolysis are In the past, splenectomy was an essential component of standard
often milder than in other hemolytic anemias because of elevated of treatment. Splenectomy results in symptomatic improvement
levels of 2,3-DPG in pyruvate kinase deficient red cells. These red from massive splenomegaly and a 40% to 70% improvement in the
blood cells permit more efficient delivery of oxygen to the tissues hematologic cell lines for up to 10 years irrespective of splenic size.
given the same concentration of hemoglobin in the blood. Splenec- Treatment with the purine analogues pentostatin and cladribine has
tomy is indicated for patients with the severe hemolytic variants of supplanted the use of interferon-alpha2, other chemotherapeutic
PKD, or patients that require significant numbers of transfusions. As agents, and splenectomy as primary therapy. These agents have
in the previous sections, splenectomy commonly is delayed until after proven response rates of 92%, with complete remission rates of 80%
the age of 5. and 10-year survival rates greater than 90%. Splenectomy rarely is
indicated for the treatment of HCL and is reserved for cases of
G6PD Deficiency incomplete response to first-line therapy, persistent splenomegaly in
Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most the absence of bone marrow involvement, atraumatic splenic rupture,
common enzyme deficiency in the world. The disease is an X-linked and severe bleeding from thrombocytopenia.
disorder of the enzyme G6PD in the glutathione pathway that leads
to damage of red cell macromolecules by toxic oxygen products. Chronic Lymphocytic Leukemia
Hemolysis can be precipitated by acute infections, oxidant drugs Chronic lymphocytic leukemia (CLL) represents a B-cell leukemia in
(sulfas and antimalarials), and fava beans. Treatment is directed at which there is progressive accumulation of functionally incompetent
inciting agent. Severe anemia is treated with transfusion. Splenec- lymphocytes. CLL arises usually after the fifth decade of life and is
tomy is rarely, if ever, indicated for the anemia associated with G6PD more common in men than in women. Splenic infiltration is common
deficiency. in advanced stages and can lead to severe splenomegaly and substan-
tial cytopenias because of hypersplenism. Splenectomy is indicated
Neoplasms and Myeloproliferative Disorders to relieve symptoms associated with massive splenomegaly, such as
abdominal pain, distension, and early satiety. Splenectomy for the
Hodgkin’s Lymphoma treatment of severe thrombocytopenia and anemia, in the setting of
Hodgkin’s lymphoma is a malignant neoplasm of lymphoreticular secondary ITP or AIHA, has a 60% to 70% hematologic response rate
cell origin that usually affects young adults in their second and third and has been shown to lead to improved overall survival.
decades. Primary treatment may consist of chemotherapy and/or
radiation. Historically, splenectomy was performed as part of a Chronic Myelogenous Leukemia
staging laparotomy that included lymph node sampling and liver Chronic myelogenous leukemia (CML) is a disorder of abnormal
biopsy. Staging laparotomy is used rarely today and largely has been proliferation and accumulation of granulocytes. Ninety-five percent
replaced by imaging modalities such as computerized tomography of CML patients will have the characteristic Philadelphia chromo-
(CT) scanning and positron emission tomography scanning. Sple- some with a reciprocal translocation between chromosomes 9 and
nectomy rarely is indicated but may be beneficial for patients who 22 [t(9;22)] leading to fusion of the breakpoint cluster region and
develop thrombocytopenia or symptoms related to splenomegaly. Abelson leukemia virus gene. CML may occur in childhood but is
found mainly in adults with a mean age of 65 at diagnosis. Diagnosis
Non-Hodgkin’s Lymphoma commonly is made during the chronic phase, which is commonly
Non-Hodgkin’s lymphoma (NHL) is the most common type of lym- asymptomatic. Splenomegaly occurs in 40% of patients in the chronic
phoma and comprises a diverse group of lymphomas varying in phase. The disease can progress to an accelerated phase with the
prognosis based on histologic subtype and clinical features. NHL development of fever, night sweats, weight loss, bone pain, increased
represents the most common primary splenic neoplasm with splenic white blood cell count, and increasing splenomegaly despite medical
involvement occurring in 65% to 80% of cases. Splenectomy is indi- therapy. An acute blastic crisis can develop, resulting in severe sple-
cated for symptoms related to massive splenomegaly and cytopenias nomegaly and hypersplenism, leading to severe anemia, bleeding
resulting from splenic sequestration. It is not uncommon for hema- complications, and infection. Current first-line therapy is with ima-
tologists to request splenectomy to assist with diagnosis to determine tinib, a tyrosine kinase inhibitor. Bone marrow transplantation or
appropriate therapy. This may occur in situations in which patients interferon-alpha can be used in cases of poor response or relapse.
have failed to respond to therapy or when inadequate tissue is avail- Splenectomy has not shown any survival benefit in the early chronic
able for proper histologic or cytometric analysis. phase or before bone marrow transplantation but may offer pallia-
There are some subtypes of NHL that involve the spleen more tion in patients with severe symptoms of splenomegaly or hemato-
than others. Splenic marginal zone lymphoma (SMZL) is an indolent logic disorders from hypersplenism.
B-cell lymphoma causing microvascular invasion of the spleen with
marginal zone differentiation that occurs in older patients. Splenec- Primary Myelofibrosis (Myelofibrosis
tomy is both diagnostic and therapeutic in SMZL. Splenectomy is an With Myeloid Metaplasia)
appropriate initial treatment and has been shown to lead to partial Primary myelofibrosis (PMF) is a chronic malignant hematologic
or complete remission in many patients because the spleen is the site disorder that results in hyperplasia of abnormal myeloid precursor
of lymphoma origin. Chemotherapy may be recommended for some cells leading to marrow fibrosis and extramedullary hematopoiesis in
patients as the initial therapy at the discretion of the referring oncol- the liver and spleen. This can lead to significant splenomegaly, cyto-
ogist, and data suggest that this is appropriate. penias from splenic sequestration, and portal hypertension from
venous thrombosis. PMF is prevalent in patients with history of
Hairy Cell Leukemia radiation or toxic industrial agent exposure. It is more common in
Hairy cell leukemia (HCL) is a rare leukemia, representing 2% of men than women with the average age of diagnosis being 65 years.
leukemias. Patients have fatigue, left upper quadrant abdominal pain, Splenectomy is indicated for patients who develop hemolysis
fever, infection, and/or coagulopathy. The disease is characterized by requiring significant transfusions, thrombocytopenia, symptomatic
B-lymphocytes that possess cytoplasmic projections from the cell splenomegaly, recurrent splenic infarctions, hypercatabolic symp-
membrane (“hairy cells”). This is an indolent disease that commonly toms (anorexia, fatigue, fever, night sweats, weight loss) and portal
occurs in the fifth decade with splenomegaly (80% to 90% of hypertension with refractory ascites and variceal hemorrhage. Sple-
patients), pancytopenia, neoplastic peripheral mononuclear cells, nectomy in PML has a substantial risk of morbidity (15% to 30%)
and bone marrow infiltration. Pancytopenia is caused by hypersplen- and mortality (10%) and only should be performed in a select
ism and replacement of bone marrow by leukemic cells. group of patients. Splenectomy in patients with PML has been
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Th e S p l e e n 607
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
608 Splenectomy for Hematologic Disorders
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Th e S p l e e n 609
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Habermalz B, Sauerland S, Neugebauer E, et al. Laparoscopic splenectomy: Price VE, Blanchette VS, Ford-Jones EL. The prevention and management of
the clinical practice guidelines of the European Association for Endo- infections of children with asplenia or hyposplenia. Infect Dis Clin North
scopic Surgery (EAES). Surg Endosc. 2008;22:821-848. Am. 2007;21:697-710.
Ikeda M, Sekimoto M, Takiguchi S, et al. High incidence of thrombosis of Somasundaram SK, Massey L, Gooch D, et al. Laparoscopic splenectomy is
portal venous system after laparoscopic splenectomy. Ann Surg. 2005;241: emerging ‘gold standard’ treatment even for massive spleens. Ann R Coll
208-216. Surg Engl. 2015;97:345-348.
Mourtzoukou EG, Pappas G, Peppas G, Falagas ME. Vaccination of asplenic
or hyposplenic adults. Br J Surg. 2008;95:273-280.
Downloaded for FK Unisba ([email protected]) at Bandung Islamic University from ClinicalKey.com by Elsevier on May 17, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.