Chapter 27: Spleen

The spleen is a dark purplish, highly vascular, coffee bean-shaped organ of mesodermal origin situated in the left upper quadrant of the abdomen at the level of the eighth to eleventh ribs between the fundus of the stomach, the diaphragm, the splenic flexure of the colon, and the left kidney (Figure 27–1). The adult spleen weighs 100-150 g, measures about 12 × 7 × 4 cm, and usually cannot be palpated. It is attached to adjacent viscera, the abdominal wall, and the diaphragm by peritoneal folds or “ligaments.” The gastrosplenic ligament carries the short gastric vessels. The other ligaments are avascular except in patients with portal hypertension or myelofibrosis.

The splenic capsule consists of peritoneum overlying a 1- to 2-mm fibroelastic layer that contains a few smooth muscle cells. The fibroelastic layer sends into the pulp numerous fibrous bands (trabeculae) that form the framework of the spleen. Corrosion cast studies demonstrate that the spleen consists of specific segments based on arterial supply numbering between two and six separated by an avascular plane.

The splenic artery enters the hilum of the spleen, branches into the trabecular arteries, and then branches into the central arteries that course through the surrounding white pulp and send radial branches to the peripheral marginal zone and the more distant red pulp. The white pulp consists of lymphatic tissue including T cells adjacent to the central artery (periarteriolar lymphoid sheets [PALS]), with a surrounding area containing lymphoid follicles rich in B cells interspersed with dendritic and reticular cells important in antigen presentation. The vascular spaces of the marginal zone between the red and white pulp channel blood into the splenic Billroth cords and out to the associated sinuses. The red pulp vascular structures have a noncontiguous basement membrane that filters cells such as senescent erythrocytes into the macrophage-lined sinuses.

Accessory spleens (spleniculi) are seen in 10%-15% of the normal population and are located primarily in the gastrosplenic, gastrocolic, and lienorenal ligaments, but they can also be found throughout the peritoneal cavity in the omentum, bowel mesentery, and pelvis. Accessory spleens probably result from a failure of infusion of splenic embryologic tissues. Ordinarily of no significance, they may play a role in recurrence of certain hematologic disorders for which splenectomy is performed. Removal of accessory spleens may lead to remission of disease in these patients. Accessory spleens are more difficult to identify with laparoscopic procedures, but the use of a hand port has allowed identification and resection of accessory spleens with a minimally invasive approach. Patients who fail to respond to initial splenectomy should undergo scanning with technetium 99m-labeled red cells or indium 111-labeled platelets to identify potential sites of missed accessory spleens and can be identified intraoperatively with a hand-held gamma counter.

Ectopic spleen (wandering spleen) is an unusual condition in which a long splenic pedicle allows the spleen to move within the peritoneum. It often resides in the lower abdomen or pelvis, where even a normal-sized spleen can be felt as a mass. The condition is 13 times more common in women than in men. Diagnostic radionuclide scan can diagnose the mass as a spleen. Acute torsion of the pedicle occurs occasionally, necessitating emergency splenectomy, and elective removal of wandering spleens in the pelvis is recommended.

The spleen has a dual function as a secondary lymphoid organ important in host immunity, and as a large filter for blood removing senescent erythrocytes and recycling iron. The anatomy of the spleen provides an ideal environment for these two functions with the immune activity in the white pulp and the hematologic function in the red pulp.

The spleen receives 5% of the total cardiac output, or approximately 150-300 mL/min, such that each red cell averages 1000 passes through the spleen each day. Normal blood cells pass rapidly through the spleen, while abnormal and senescent cells are slowed and entrapped. As they travel through the hypoxic, acidotic, glucose-deprived splenic cords and sinuses of the red pulp, senescent erythrocytes pass into the vascular spaces and are phagocytosed by macrophages in a process called “culling.” Part of the membrane of erythrocytes can be removed through the gaps between endothelial cells lining the vascular spaces in a similar process called pitting. In the presence of splenomegaly and other disease states, the flow patterns of the spleen become more circuitous as the red pulp volume expands, so that even normal cells may be trapped.

The spleen is considered to be a secondary organ of the immune system and represents the largest single collection of lymphoid tissue in the body. The white pulp of the spleen contains the various cellular components needed to generate an immune response, with structural and functional relationships similar to those of lymph nodes. Lymphocytes and circulating antigen-presenting cells enter the white pulp via the marginal zone capillaries and traverse the T cell-rich PALS before passing through bridging channels into the red pulp. Primary follicles or germinal centers with secondary follicles at the periphery of the white pulp are sites of B cell expansion and immunoglobulin production. Blood passing through the spleen is exposed to all the key cellular components necessary for both humoral and cellular immune responses. Tissue macrophages in the spleen are key components of generating an immune response particularly in encapsulated organs. Moreover, the concentration of ­macrophages in the red pulp vascular spaces facilitates opsonization of particles coated with IgG and plays an important role in the filtration and removal of senescent erythrocytes, the autoimmune hematologic diseases as well as explaining the increased risk of sepsis that follows splenectomy in children under 2 years of age. Even in adults, splenectomy leads to a slight but definite reduction in immune function.

Normally, about 30% of the total platelet pool is sequestered in the spleen. Splenomegaly typically involves expansion of the red pulp, which increases this sequestration to between 80% and 95% of the platelet cell mass. Storage of erythrocytes and granulocytes in the spleen is limited in humans, but newly formed reticulocytes released from the bone marrow concentrate in the spleen to undergo a maturational process.

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 would include treatment of simple cysts, echinococcal cysts, splenic abscess, and various benign neoplasms including hamartomas, hemangiomas, lymphangiomas, and rare malignant lesions.

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 of this would be 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 due to 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 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 of splenectomy. Each of these categories of disease will be discussed including the etiology and pathophysiology of the disorder, the specific indications for splenectomy, alternative treatments, and the results of splenectomy.

HYPERSPLENISM

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 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, or (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 for splenectomy.

Clinical Findings

A. Symptoms and Signs

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 varices.

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.

B. Laboratory Findings

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 due to sequestration of platelets but also possibly due to 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.

C. Evaluation 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 crossing the abdominal midline are frequently seen.

Differential Diagnosis

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 (ITP), the spleen is normal or only slightly enlarged. In aplastic anemia, the spleen is not enlarged and the marrow is fatty.

Treatment & Prognosis

The course, response to treatment, and prognosis of the hypersplenic syndromes differ widely depending on the underlying disease and its response to treatment and will be discussed for each particular disorder below. The indications for splenectomy are given in Table 27–2.

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 upon 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

Neoplastic diseases in which splenectomy may play a role in the 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.

1. Chronic Lymphocytic Leukemia

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% 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 operative morbidity.

2. Hairy Cell Leukemia

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 analogues 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 rituxamib and alpha interferon.

3. Myelodysplastic Syndrome

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/mL). The platelet count may be elevated, but values less than 100,000/mL 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 are indicated. Newer therapies include treatment with immunomodulatory drugs such as thalidomide or antibodies to VEGF and TNF. 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.

4. Systemic 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 alpha interferon has been shown to be effective.

METABOLIC DISORDERS

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.

1. Gaucher Disease

Gaucher disease is an autosomal recessive disorder characterized by a deficiency in beta-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 from either the direct effects of the size of the spleen or secondary to cytopenias from hypersplenism.

Treatment & Prognosis

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 increase 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.

2. Wiskott–Aldrich Syndrome

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/mL and 40,000/mL, 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.

Treatment & Prognosis

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 an 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.

3. Chédiak–Higashi Syndrome

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.

4. Sarcoidosis

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.

ERYTHROCYTE DISORDERS

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.

1. Hereditary Spherocytosis

General Considerations

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 all, 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 by splenectomy.

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 three decades.

Clinical Findings

A. Symptoms and Signs

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.

B. Laboratory Findings

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.

Differential Diagnosis

At present there is no pathognomonic test for hereditary spherocytosis. 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 burns.

Complications

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.

Treatment

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 the spleen.

Prognosis

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.

2. Hereditary Elliptocytosis

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 cholecystectomy if gallstones are present. The red cell defect persists after splenectomy, but the hemolysis and anemia are cured.

3. Hereditary 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.

4. Thalassemia 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.

AUTOIMMUNE DISORDERS

The production of IgG autoantibodies specific for cell membrane proteins on erythrocytes causes autoimmune hemolytic anemia; on platelets, it causes 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 Fc receptor.

1. Acquired Hemolytic Anemia

General Considerations

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 antibodies may.

Although hemolysis without demonstrable antibody (Coombs test-negative) 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 (Coombs test-positive). 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).

Clinical Findings

A. Symptoms and Signs

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.

B. Laboratory Findings

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).

Treatment

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 cross-matching 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.

Prognosis

Relapses may occur after splenectomy but are less frequent if the initial response was good. The ultimate ­prognosis in the secondary cases depends upon the underlying disorder.

2. Immune Thrombocytopenic Purpura (Idiopathic Thrombocytopenic Purpura)

General Considerations

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. Five to 15% of HIV-positive patients 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.

Clinical Findings

A. Symptoms and Signs

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.

B. Laboratory Findings

The platelet count is moderately to severely decreased (always below 100,000/mL), 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.

Differential Diagnosis

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

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 eltrambopag are being studied as third line medical therapies.

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 is effective.

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) achieve 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.

Prognosis

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 TP has increased. Agents to stimulate TPO may have significant benefit for patients who have no improvement in platelet count after splenectomy.

3. Felty’s Syndrome

Approximately 1% of patients with rheumatoid arthritis have splenomegaly and neutropenia—a triad known as Felty’s 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’s 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.

4. Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura 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.

Treatment & Prognosis

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.

VASCULAR DISORDERS 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 (discussed in Chapter 34).

1. Splenic Vein Thrombosis

Etiology

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 on 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.

Diagnosis

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 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.

Treatment & Prognosis

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.

2. Cysts & Tumors of the Spleen

Parasitic cysts are almost always echinococcal (see Chapter 8). 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.

INFECTIONS OF 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.

DIAGNOSTIC SPLENECTOMY

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.

Splenic Mass Lesions

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; 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 hemangiomas.

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—would 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.

Splenomegaly 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.

Staging Laparotomy for Hodgkin Disease

Another type of diagnostic procedure would be 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 based on 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.

IATROGENIC SPLENECTOMY

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, the spleen should be attempted to be preserved to decrease the risk of postsplenectomy sepsis.

INCIDENTAL SPLENECTOMY

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 post-splenectomy 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 Hyposplenism above), 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.

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.

Preoperative preparation of patients undergoing elective splenectomy should correct coagulation abnormalities and deficits in red cell mass, treat infections, and control immune reactions. Because platelets are removed so rapidly from the circulation, they usually are not given for thrombocytopenia until after the splenic artery has been ligated. Antibodies in the patient’s serum may complicate cross-matching of blood. Many patients with autoimmune disorders require corticosteroid coverage in the perioperative period. For emergency splenectomy, hypovolemia should be corrected by whole blood transfusions. For elective cases, prophylactic vaccination with a polyvalent pneumococcal vaccine that protects against a common encapsulated offending organism in postsplenectomy infection is recommended. Elective splenectomy is now most commonly performed as a laparoscopic procedure. This reduces the recovery period and is significantly better tolerated by most patients.

Details of surgical technique are not within the scope of this text, but it should be noted that there are two approaches to open splenectomy (Figure 27–2). In one, which is of value chiefly in traumatic rupture of the spleen, the organ is immediately mobilized and the splenic artery is secured from behind as it enters the hilum. In the other, which is of vital importance in the removal of massively enlarged spleens, the organ is left in situ. The gastrocolic ligament is opened, and the splenic artery is ligated as it courses along the upper edge of the pancreas. This permits blood to leave the spleen through the splenic vein while all other ­attachments (ie, the short gastric vessels and colic attachments) are divided before the spleen is delivered. This method permits the removal of massively enlarged vascular spleens with practically no loss of blood.

Splenorrhaphy is operative repair of the spleen following trauma. The principles of splenorrhaphy are to debride the devitalized tissue and to attempt to approximate the normal contour of the spleen with capsular sutures or external wraps of material. Partial splenic resections may be performed for trauma or for disease states in which splenic debulking is indicated but may be unsuccessful with a higher immediate complication rate. Partial splenectomy for Gaucher disease, large cysts, or benign tumors has been reported using automatic stapling devices as well as microwave coagulators. On the other hand, for autoimmune disorders, it is absolutely essential for cure to remove the spleen completely including excision of accessory spleens. There may be some benefit to obtaining a preoperative nuclear scan and intraoperative identification with a hand-held gamma counter.

Massive splenomegaly is defined as a spleen weight of greater than 1500 g or 8 to 10 times the normal size. Disease processes leading to massive splenomegaly include lymphoma, leukemia, and metabolic storage diseases. The morbidity and mortality rates of splenectomy for massive splenomegaly are increased primarily as a result of the risk of severe and rapid intraoperative blood loss. The operative approach in these cases is initial ligation of the splenic artery through the lesser sac at the superior border of the pancreas. Next, ligation of the short gastric vessels along the greater curvature all the way to the gastroesophageal junction is performed, allowing the stomach and left lobe of the liver to be retracted away from the spleen. Only after decreasing the splenic arterial inflow by the above maneuvers should mobilization of the lateral and superior attachments be performed, leading to removal of the massive spleen.

Laparoscopic splenectomy is now the standard of care in most major centers with high volumes of splenic surgery. Virtually any indication for elective splenectomy qualifies for a laparoscopic approach, including patients with severe thrombocytopenia, patients with massive splenomegaly, patients needing partial splenectomy, and for the removal of accessory spleens and the wandering spleen. Contraindications to laparoscopic splenectomy include portal hypertension and severe co-morbid disease. With improved techniques, laparoscopic partial splenectomy has now been reported for focal mass lesions and hereditary hematologic diseases.

Laparoscopic splenectomy is performed typically using four ports. Midline ports for the cannula as well as for retraction of the stomach away from the splenic hilum are placed. Left subcostal ports are used as operating sites for dissection of the splenic hilum. An angled laparoscope is required for visualization of the superior and lateral attachments of the spleen. Vessels are divided with clips, sutures, or stapling devices. Precise exposure of the hilum with gentle upward traction on the spleen to stretch and expose the vessels is preferred to blind stapling of the hilum. Clinical conditions such as ITP and hereditary spherocytosis are the most common indications for laparoscopic splenectomy as the spleen is of normal size. Search via the laparoscope for accessory spleens is important in these procedures for a successful outcome, and this may be facilitated by the use of a hand port for palpation.

HEMATOLOGIC EFFECTS OF SPLENECTOMY

Absence of the spleen in a normal adult usually has few clinical consequences. Red cell count and indices do not change, but red cells with cytoplasmic inclusions may appear, eg, Heinz bodies, Howell–Jolly bodies, and siderocytes. Granulocytosis occurs immediately after splenectomy but is replaced in several weeks by lymphocytosis and monocytosis. Platelets are usually increased, occasionally markedly so, and may stay at levels of 400,000-500,000/mL for over a year. Even more striking thrombocytosis (eg, 200,000-300,000/mL) may develop after splenectomy for hemolytic anemia. A platelet count of over a million is not an indication for anticoagulants, but antiplatelet agents such as aspirin may help prevent thrombosis.

POSTSPLENECTOMY SEPSIS & OTHER POSTSPLENECTOMY PROBLEMS

Complications related to splenectomy per se are relatively few, with atelectasis, pancreatitis, and postoperative hemorrhage being the most common. If splenectomy is done for thrombocytopenia, secondary bleeding may occur even though the platelet count usually rises promptly. Platelet transfusions should be given if primary hemostasis is abnormal (ie, oozing occurs) and the platelet count remains low. Thromboembolic complications may be more common following splenectomy, but this complication does not correlate with the degree of thrombocytosis. The risk of portal vein thrombosis is 3% and occurs most commonly after splenectomy for massive spleens hemolytic anemia and not after trauma or splenectomy for thrombocytopenia. Symptoms include fever, abdominal pain, diarrhea, and abnormal liver function tests. Treatment consists of anticoagulation plus antibiotics.

Individuals are more susceptible to fulminant bacteremia after splenectomy and have been reported between 1 week and greater than 20 years after splenectomy. This is a result of the following changes that occur after ­splenectomy: (1) decreased clearance of bacteria from the blood, (2) decreased levels of IgM, and (3) decreased opsonic activity. The risk is greatest in young children, especially in the first 2 years after surgery (80% of cases) and when the disorder for which splenectomy was required was a disease of the reticuloendothelial system. In general, the younger the patient undergoing splenectomy and the more severe the underlying condition, the greater the risk for developing overwhelming postsplenectomy infection. There is a low but significant risk of infection even in otherwise normal adults following splenectomy. Most of these infections occur after the first year, and nearly half occur more than 5 years after splenectomy. Lethal sepsis is very rare in adults. There is a distinct clinical syndrome: mild, nonspecific symptoms are followed by high fever and shock from sepsis, which may rapidly lead to death. Streptococcus pneumoniae, Haemophilus influenzae, and meningococci are the most common pathogens. Disseminated intravascular coagulation is a common complication. Awareness of this fatal complication has led to efforts to avoid splenectomy or to perform partial splenectomy or splenic repair for ruptured spleens (analogous to surgical management of liver trauma) to maintain adequate splenic function. Splenic autotransplantation may also achieve partial restoration of splenic function after splenectomy.

The risk of fatal sepsis is less after splenectomy for trauma than for hematologic disorders, probably due to splenic autotransplantation. Prophylactic vaccination against pneumococcal sepsis should be used in all surgically or functionally asplenic patients. Since splenic function may be important in the immune response to vaccine, early administration of polyvalent pneumococcal vaccine (Pneumovax) is advisable. The vaccine provides protection in adults and older children for 4-5 years, after which revaccination is advisable. Since the vaccine is only effective against about 80% of organisms, some authorities have recommended a 2-year course, treatment until age 16, or lifelong prophylaxis with penicillin following splenectomy. Others have advocated use of ampicillin to provide coverage for Haemophilus influenzae as well as pneumococci. Antibiotic prophylaxis is essential in children under 2 years of age and should be continued until at least age 6. In general, splenectomy should be deferred until age 6 unless the hematologic problem is especially severe.