The 20th century brought technical advances in terms of hemostasis and blood transfusion as well as an understanding of the pathophysiology of splenic function.⁴ The spleen was identified as the site of red cell destruction in autoimmune hemolytic anemia by Micheli in 1911. Paul Kaznelson, who was a Czech medical student, postulated that the removal of the spleen in patients with idiopathic thrombocytopenic purpura would be of benefit and, in 1916, he reported the successful treatment of a patient with that disease with splenectomy. Throughout the 20th century, as the understanding the pathophysiology of hematologic and immune disorders associated with the spleen increased, it became clearer the roles for splenectomy that are pertinent to modern-day practice.

EMBRYOLOGY AND ANATOMY

1 The spleen develops from the mesoderm as an outpouching from the mesogastrium during the 5th week of gestation^4–6 with the natural rotation of the gut during subsequent development placing the spleen in its typical position in the left upper quadrant of the abdomen (Fig. 73-1). In that location, the spleen relates to the diaphragm both superiorly and laterally, and it generally spans the 9th, 10th, and 11th ribs along the left mid to posterior axillary line. The ventral surface of the spleen relates to the greater curvature of the stomach and the tail of the pancreas. The tail of the pancreas touches the splenic capsule in 30% of cases and is 1 cm away in 70% of cases. The inferior pole relates to the left kidney posteriorly and the splenic flexure of the colon anteriorly.

The normal size of the spleen is approximately 13 × 7 × 4 cm.⁵ The typical weight of a spleen in a young adult is felt to be 150 to 200 g and this decreases to approximately 100 g in the elderly population (Fig. 73-2).^7,8 It is felt that the spleen must double in size to the range of 300 to 400 g to project below the costal margin to allow palpation of the spleen tip on abdominal examination in a patient undergoing deep inspiration.⁹ The weight assigned to the spleen in defining massive splenomegaly has been arbitrarily set at 1,500 g or 10 times the average adult splenic weight. There can be a significant cleft in the capsule of the spleen that may be confused with splenic disruption on CT scan obtained for trauma.

The vascular anatomy of the spleen is rather straightforward.¹⁰ The splenic artery is one of the three major trunks along with the left gastric artery and common hepatic artery branching off from the celiac axis (Fig. 73-3). This artery has a characteristic appearance on celiac arteriograms as a serpentine artery with loops extending both superiorly and inferiorly. There are several small pancreatic branches that supply blood to the body and tail of the pancreas along the lengths of this vessel. The first major splenic branch occurs approximately 2 to 3 cm from the hilum and it is called the superior polar artery. The main artery then divides into anywhere between three and five segmental branches that enter along the trabeculae of the spleen. Additional blood supply to the spleen comes from the left gastroepiploic artery via the short gastric vessels. When the spleen is massively enlarged, it may have direct vessels that are parasitized from the omentum, diaphragm, or the mesentery of the splenic flexure of the colon. The splenic artery generally travels outside the parenchyma of the pancreas just at the superior border although loops that go inferiorly may be completely covered by the posterior surface of the pancreas whereas superior loops may be well away from the pancreatic surface. It is these more cranially located curves that are the optimal place to provide a ligature for control of the splenic artery during procedures in which there is significant thrombocytopenia or for enlarged spleens. These are generally areas that have few pancreatic branches and avoid proximity to the splenic vein that occurs when the artery loops inferiorly.

The splenic vein is formed by segmental venous branches that leave the trabeculae and coalesce into the main splenic vein in the hilum of the spleen (Fig. 73-3). The splenic vein is intimately associated with the posterior surface of the tail and body of the pancreas to its junction with the superior mesenteric vein forming the portal vein. The inferior mesenteric vein may join the splenic vein directly at several areas along its course or may come together right at the junction of the superior mesenteric vein. There are again several pancreatic branches that directly enter this splenic vein. The blood flow to the spleen in the typical adult is estimated to be 200 to 300 mL/min or approximately 5% of the cardiac output.¹⁰

The lymph node drainage generally follows the vasculature. The primary lymph nodes are located in the hilum of the spleen and also along the splenic artery at the superior border of the pancreas and along the short gastric vessels.

There are several ligaments that maintain the spleen in its fixed position in the left upper quadrant (Fig. 73-4).⁶ Three of these ligaments are virtually always present (except in the condition of the “wandering spleen”)¹¹ and two may be present to variable extents, depending on the individual patient and the disease process. The first ligament that is constant is the splenogastric ligament that is a left-sided superior extension of the greater omentum along the proximal greater curvature of the stomach. Within this area supplied by the left gastroepiploic vessels are short gastric vessels that branch to the upper pole of the spleen and often provide the upper two-thirds of the spleen with alternative blood supply. The second and very important ligament is the splenorenal ligament that runs parallel to the posterolateral border of the spleen and attaches this to the superior pole of Gerota fascia developing the left kidney. This ligament is divided when mobilizing the spleen during splenectomy and allows reflection of the spleen with or without tail of the pancreas medially. The splenocolic ligament is short and may be avascular or have small blood vessels that go from the inferior tip of the spleen to the splenic flexure of the colon. This may be divided by cautery or may have vessels that need controlled with ties or clips during mobilization of the splenic flexure of the colon.

Two ligaments that are variably present are the spleno- omental attachments and the splenophrenic attachments (Fig. 73-4). The free part of the greater omentum may have variable association with the splenic capsule along the inferior pole. There are often small vessels that may be controlled by electrocautery. This attachment may be absent or may be quite extensive over the lower pole of the spleen. It is this attachment to the omentum that often leads to disruption of the capsule along this inferior pole causing bleeding in other abdominal procedures and may even eventually result in splenectomy for control with an inadvertent injury. Before exerting inferior traction on the omentum during any procedure, the extent of attachments to the lower pole of the spleen should be investigated and, if present, should be divided prior to more vigorous mobilization. There may be direct ligaments connecting the spleen to the diaphragm identified as splenophrenic ligaments. These typically are present to a greater degree when the spleen is diseased or enlarged. They may be avascular or may have branches of vessels parasitized from the diaphragm blood supply especially with large spleens.

The anatomy of the spleen itself is segmental being fed by arteries and drained by veins that leave via the trabecula.¹² The trabeculae are fibrous bands that attach to the splenic capsule. The parenchyma of the spleen in between these trabeculae is divided into a small area of white pulp surrounding the arteries, a marginal zone, and the larger predominant area of red pulp that comprises 75% of the splenic parenchyma.^13,14 The capsule of the spleen is quite thin as it is only a few cells layers thick. This consists of a single layer of mesothelium and several layers of fibroelastic tissue. In other mammals but not humans, there may be variable amounts of smooth muscle in the capsule. This smooth muscle would allow contraction and mobilization of the circulating blood cells that are stored in the spleen.¹⁵ The trabecular arteries that enter the spleen as continuation of the segmental arterial branches then give off perpendicular branches to form the central arteries (Fig. 73-5). Surrounding these central arteries is the periarterial lymphatic sheath that is composed of T lymphocytes as well as follicles with B cells at various stages of development. During the antigenic stimulation, this area greatly expands with more mature and secondary follicles. The marginal zone is the borderline between the white pulp and the red pulp and contains a mixture of lymphatics and macrophages. The structure of the red pulp is made up of splenic cords with an intervening area called splenic sinuses. The splenic cords, also known as the cords of Billroth, are a meshwork of fibroblasts and a large number of mature macrophages. The splenic sinuses are an interconnective meshwork of fairly random red cell spaces that are thin walled and generally filled with large numbers of erythrocytes.¹⁴

Studies on blood flow show two alternative routes to the spleen being fast flow and slow flow.¹⁶ A small proportion of the blood goes through the splenic arteries and returns rapidly to the splenic veins. This fast flow pattern consists of a greater predominance of plasma and few erythrocytes because of streaming and accounts for only 10% of flow. A particularly large portion of the erythrocytes that enter the spleen travel through the highly fenestrated meshwork in the red pulp as part of the filtration process of the spleen. This slow path or slow flow comprises up to 90% of the splenic blood flow and relates to the role of the spleen in clearly senescent erythrocytes.

2 Accessory spleens are small nodules of splenic tissue that are completely separate from the main body of the spleen. They typically range in size from 0.5 cm up to 3–4 cm. The reported incidence of accessory spleens ranges between 10% and 20%. The most common location for these small nodules of splenic tissue is in the splenic hilum, the omentum most commonly between the stomach and transverse colon but also within the greater omentum, and the small bowel mesentery. However, they can occur virtually anywhere in the abdomen including the retroperitoneum behind the spleen and in the pelvis. Accessory spleens are important in disease processes in which a complete removal of all splenic tissue is mandatory for long-term cure such as certain autoimmune disorders. A preoperative nuclear medicine spleen scan may also be helpful in some circumstances to identify sources of residual splenic tissue,¹⁷ particularly when present in less common locations.

PHYSIOLOGY

The major functions of the spleen can be divided into two general categories of hematologic functions and immunologic functions (Table 73-2).¹⁴ For hematologic functions, the spleen primarily is an organ related to the destruction or clearance of the circulating blood cell elements as a normal physiologic mechanism. This physiologic filtration function is increased in disease states that produce hypersplenism. The spleen may play a minor role in hematopoiesis and storage of blood cells that can be mobilized for the circulation with the predominantly stored cell being platelets predominantly platelets. In terms of the immunologic functions, the spleen relates to the vascular system in many of the same ways that lymph nodes relate to the lymphatic system. The white pulp and marginal zones are most important for the immunologic functions, whereas the red pulp is primarily related to the hematologic functions. However, the macrophages that line the cords or fill the cords in the red pulp are clearly also important for immunosurveillance for intravascular pathogens.

3 The primary hematologic function of the spleen is removal of senescent erythrocytes or remodeling of abnormal red blood cells with various deformities and the recycling of iron by splenic macrophages.¹⁴ The average life span of a normal erythrocyte measured on clearance studies in humans is estimated to be approximately 120 days.¹⁸ It is also estimated that the spleen destroys approximately 100 billion erythrocytes daily in the red pulp. The process of removal or phagocytosis of erythrocytes or other blood cells is called culling. The blood flow patterns of the spleen lead to a hemoconcentrated erythrocyte-laden fluid that enters the sinuses of the red pulp. Here a slow flow through the sinusoid network with adjacent macrophage filled cords leads to the environment in which erythrocytes may become trapped and then phagocytized by the macrophages. The precise mechanism by which senescent red cells are identified for destruction in normal physiology is unclear. One hypothesis would be that over the course of the life span of an erythrocyte, there is loss of either membrane elements or total membrane material such that the red cells become less compliant and therefore become trapped in the mesh of the sinusoids. A second hypothesis is that specific cell surface marker molecules may become either more exposed or less available to allow identification of senescent cells targeted for destruction. Pathologic destruction of red cells occurs in diseases such as hereditary spherocytosis or elliptocytosis in which genetic defect creates abnormal red cell pliability limiting its passage through the red pulp. Similarly, in sickle cell anemia, the genetic defect in the hemoglobin alters red cell shape and creates destruction with clogging of the sinusoids. A second pathologic mechanism in which destruction of red cells is increased is in disease processes in which there is an increase in red pulp volume, a condition known as hypersplenism.

The second physiologic process involving circulating erythrocytes is remodeling or pitting that is partial removal of the cell membrane typically associated with the cytoplasmic inclusions. Erythrocytes with a remnant of the cell nucleus remaining pass more slowly through the splenic red pulp because of their larger size.¹⁴ The nuclear remnant may be trapped passing through a small space in the spleen and this solid particle that does not allow deformation gets pinched off in the process of pitting. Intracytoplasmic inclusions include Howell–Jolly bodies that are nuclear remnants, Heinz bodies that are denatured hemoglobin, and Pappenheimer bodies that are iron granules.

The destruction of the other circulating cellular elements of the blood (platelets and leukocytes) is more in the realm of pathophysiology of the spleen than normal physiologic function. The disease processes in which these cells are removed are related to either autoantibodies to cell surface elements or hypersplenism. If either platelets or white blood cells become coated with antibodies, the Fc portion of the immunoglobulin will interact with the Fc receptors on the macrophages in the splenic cords leading to phagocytosis of these cell types. With splenic enlargement from various causes of hypersplenism, a similar process of destruction may occur even without any autoantibodies or defects in the cells just because of an increase in splenic mass.

The spleen serves as a potential source for hematopoiesis of all cell types during gestation. In normal humans, there is felt to be very little if any production of red cells, granulocytes, or platelets, which is not the case in other mammals. In the white pulp of the spleen, there are germinal centers with amplification and production of reactive lymphocytes. The cords of the spleen are filled with macrophages and throughout normal adult life there may be production of lymphocytes and macrophages in the spleen. In certain disease states, the spleen may develop the capacity for erythropoiesis and myelopoiesis. The best example is agnogenic myeloid metaplasia (AMM), discussed in more detail later. In this disease, the bone marrow is replaced with fibrotic scar and a portion of the hematopoietic function of the marrow is taken over by the spleen that is typically quite enlarged.

The final hematologic function of the spleen may be as a reservoir of circulating cellular elements.¹⁵ In humans, the only significant cell type that is stored in the spleen is platelets and it is estimated that 30% of all platelets may reside in the spleen. This function may be more important than other mammals particularly those with significant smooth muscle lining the capsule of the spleen that allows contracture with expulsion of large numbers of stored cells as a physiologic response to injury.

4 The immunologic function of the spleen is primarily to generate an immune response to antigens that are identified and cleared from the blood system. Either opsonized antigens or specific encapsulated microorganisms are important examples of target antigens trapped by the spleen. The spleen is an ideal environment for generation of either a cellular or humoral immune response. There are all of the necessary cells types for stimulation of the immune response including phagocytic cells, dendritic cells, T cells, and B cells that may form general follicles to generate specific antibody responses. These interactions primarily occur in the marginal zone in the white pulp that may become quite enlarged and hypertrophied during antigen stimulation. These cellular components and the structure of the germinal follicles are essentially identical to those found in lymph node tissue that becomes enlarged in a similar way with antigenic stimulation via microbes or antigens in the lymphatic system.

The spleen is also involved in nonspecific immune responses. It is the site of synthesis of both properdin and tuftsin that are opsonins. Tuftsin is a small peptide that binds to the surface of granulocytes and promotes phagocytic function by these cells.¹⁹ Properdin can initiate the alternate pathway of complement activation that may be important in destruction of abnormal cells or bacteria that are antibody bound. The spleen is not the only source of these nonspecific immune-enhancing proteins and therefore splenectomy may lead to only a modest alteration in this function.

PATHOPHYSIOLOGY

There are characteristic responses that share many common features under the broad category of hyposplenism and hypersplenism. These features highlight the normal physiologic functions of the spleen and provide guidelines and influence clinical decision-making when managing patients after splenectomy or in deciding which patients should undergo splenectomy.

Hyposplenism

By far, the most common cause of hyposplenism is surgical removal.²⁰ Other explanations would be an unusual situation of a congenitally small or absent spleen or acquired destruction of splenic tissue as occurs in sickle cell anemia or celiac disease. The diagnosis can be verified by 99Tc-labeled spleen scan or pitted red blood cell count. Pathophysiologic consequences of hyposplenism or the changes seen after a splenectomy are predictable from the known functions of the spleen. There are hematologic changes in the circulating cells that can be predicted from the splenic functions of culling, pitting, and as a reservoir for platelets (Table 73-3). There are changes in the immunologic responses that are important primarily in infants or young children, which can lead to the problem of overwhelming postsplenectomy sepsis. There are a variety of other causes for hyposplenism listed in Table 73-4.

The changes in circulating blood cells after splenectomy in cases of hyposplenism affect the erythrocytes, leukocytes, and platelets. Over time, the intracytoplasmic inclusions in the red cells that are normally cleared by the spleen accumulate resulting in presence of Howell–Jolly bodies, Heinz bodies, and Pappenheimer bodies as well as target cells with excess red blood cell membrane and occasionally increase in the circulating nucleated red blood cells or reticulocytes. As the spleen is the organ of storage for a large proportion of the platelets, a splenectomy often results in thrombocytosis with platelet counts postsplenectomy ranging between 500,000 and up to one million in some cases. This increased platelet count tends to be transient and may be a reflection of the fact that the spleen while being a storage organ for platelets may not be a primary area of platelet destruction after the typical half-life of 10 days. The immediate response after a splenectomy in white cells is leukocytosis again reflecting storage of a large proportion of white cells in the spleen.²¹ As with the thrombocytosis, this effect is transient but there may be long-term increases in the proportion of circulating lymphocytes and monocytes after the splenectomy. Preserving even a small amount of spleen can preserve splenic function in clearing senescent blood cells.²²

Clinical sequelae of hyposplenism or following splenectomy are discussed in more detail at the end of this chapter.

Hypersplenism

Hypersplenism is increased splenic function that is manifested clinically by the decrease in one or more of the circulating blood elements. The specific criteria for hypersplenism are: (1) documented anemia, thrombocytopenia, or leukopenia; (2) normal compensatory response by the bone marrow to correct the cytopenia; and (3) correction of this cytopenia by splenectomy. Some definitions of hypersplenism may also include the criteria for splenomegaly. This more restrictive definition would not necessarily incorporate, however, diseases or disorders related to abnormalities in circulating blood cells such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia. The second approach to categorizing hypersplenism is to classify the disorders on the basis of whether the primary abnormality is in the circulating blood cells versus in the spleen itself (Table 73-5). For either situation, the pathophysiology is that the spleen is the site of destruction for one or more circulating blood elements. In cases of significantly enlarged spleen, additional symptoms relate to mass effect from the spleen on adjacent organs. The most important symptom is early satiety and weight loss as the stomach is compressed between the liver and the enlarged spleen. There are a variety of causes of hypersplenism that are typically neoplastic but may be related to primary blood cell dysfunction or abnormalities or other condition such as portal hypertension due to cirrhosis or splenic vein thrombosis. Hypersplenism is the most important indication for elective isolated splenectomy²¹ to reverse the cytopenia and often to relieve compressive symptoms from splenomegaly.

SURGICAL TREATMENT FOR DISEASES RELATING TO THE SPLEEN

Until fairly recently, the only pertinent operation to discuss in relationship to disease involving the spleen was open splenectomy. Appreciation of the increased risk of infection in inpatients who are asplenic or hyposplenic in the late 1960s and the early 1970s led to two new surgical procedures. First, there was an interest in splenic preservation in cases of trauma with procedures including splenorrhaphy and other types of ways to save damaged spleen. Second, procedures to do partial splenectomy were developed primarily for elective surgery in which hypersplenisim existed but a complete splenectomy was not necessary and there were advantages to partial splenectomy. The most recent change in surgery of the spleen relates to the explosion in the minimally invasive surgery that has happened over the past 25 years.²³ The spleen is very susceptible to a laparoscopic excision and recent reports have utilized laparoscopic splenectomy for virtually all indications including to remove massive spleens. Despite its increasing utilization in most major centers, though, laparoscopic splenectomy still appears to constitute only a minority of the splenectomy procedures performed nationally.

Indications for Splenectomy

To better describe and understand operative indications in surgery of the spleen, one could categorize splenectomy or procedures of the spleen into eight general areas:

1. Trauma or injury to the spleen.

2. Autoimmune/erythrocyte disorders. In this category of disease, there are specific cytopenias related to antibodies targeting platelets, erythrocytes, or neutrophils with the second category of diseases related to intrinsic structural changes within the erythrocyte. For these disorders, total splenectomy is typically indicated for cure.

3. Hypersplenism results in decreased circulating blood cells often including all subtypes of platelets and red blood cells. Hypersplenism may be related to neoplastic infiltration of the spleen or infiltration with lipids and other stored products that lead to massive spleen. Hypersplenism may cause symptoms due to the splenic size.

4. Incidental splenectomy. The spleen may be removed as part of a standard operation to remove the distal pancreas most commonly, and also for proximal gastric cancers due to the direct or nodal involvement. Other enlarged tumors of the left upper quadrant and retroperitoneum such as sarcoma and adrenal tumor, and left-sided renal cell cancers, may require splenectomy because of association of these tumors with the spleen or its vessels.

5. Iatrogenic splenectomy. This is a category that may be underreported but includes splenectomy or splenic preservation procedures due to inadvertent injury to the spleen during surgery for other reasons within the general abdominal cavity or, specifically, the left upper quadrant.

6. Diagnostic procedures. This category of splenectomy includes cases when the spleen is removed primarily to make a clinical diagnosis when none is available.²⁴ A subcategory of this would be staging laparotomy for Hodgkin disease that is rapidly becoming more of a historical footnote as the treatment of this lymphoma now rarely requires splenectomy.

7. Vascular abnormalities. Splenectomy for vascular events or abnormalities includes patients with splenic vein thrombosis or less commonly splenic artery aneurysms.

8. Miscellaneous procedures. This would include treatment of simple and neoplastic cysts, echinococcal cysts of the spleen, and treatment of the symptomatic “wandering spleen,” a congenital anomaly.

An estimated 22,000 splenectomies are performed annually in the United States.²⁵ Two recent reports have been published describing 10-year experiences for all splenectomies done in their respective institutions. The first report is the combined series of 1,280 splenectomies over a 10-year interval from the Barnes Hospital in St. Louis and the Brigham and Women’s Hospital in Boston.²⁴ The second report is a single institution over the identical time period from Vanderbilt University.²⁶ In the Barnes/Brigham series, there were 1,280 splenectomies, and in the Vanderbilt series there were 896 splenectomies (see Table 73-6). One can see that dependent on the type of institution and referral patterns, the indications for splenectomy vary to some degree. In the Vanderbilt series, the majority of splenectomies are done for trauma, which account for 41.5% of all operations done in that institution. In the Barnes/Brigham & Women’s series, the most common indication was incidental splenectomy in which the spleen was removed as part of an excision of another organ, typically large tumor somewhere in the left upper quadrant of the abdomen. The second most frequent indication for splenectomy was staging laparotomy for Hodgkin disease. This is likely to be different in the ensuing decade as both treatment indications and diagnostic techniques have significantly eliminated this practice after 1990. These differences highlight that indications for splenectomy can vary dramatically among centers, in part related to trauma volume at the centers and cancer case referrals. It also should be noted that if one eliminates the traumatic, incidental, and staging procedures, the most common indication in both series relates to autoimmune or erythrocyte disorder.

The details of the indications for splenectomy in each of these categories are discussed. The specific indications for splenectomy (whether total or partial), the alternative treatments that are available, and the results from surgical removal of the spleen are also reviewed.

Trauma of the Spleen

5 The spleen is the most common intra-abdominal organ injured by blunt trauma in the United States and in many institutions splenectomy remains the most common operative procedure performed on the spleen.²⁷ The history of splenic surgery mirrors the history of surgery for trauma. In the ancient medical literature, there have been reports of resection of portions of the spleen that had herniated through a flank wound.²⁸ The first documented splenectomy for penetrating trauma occurred in San Francisco by a British naval surgeon named O’Brien in 1816 when a spleen protruded out the side of a knife wound.¹² In the late 19th century, Theodor Billroth observed during an autopsy of a patient who died of head trauma 5 days earlier that there was minimal blood in the peritoneum from the fracture of the splenic capsule and predicted that these injuries might be managed operatively. Although in the earlier part of the 20th century, splenic trauma was uniformly managed by a complete splenectomy, Dr. Campos Christo of Brazil reported partial splenectomy and splenic salvage for both penetrating and blunt trauma in 1962 (Table 73-1).⁴ This initial report, combined with the ability to obtain repeated cross-sectional imaging and with the understanding of splenic function, has led to the current management guidelines of nonoperative management for lower-grade splenic injuries and operative management centered around splenic preservation when possible.²⁹

The most common modes of blunt injuries leading to splenic rupture are motor vehicle accidents as well as bicycle accidents in which upper abdominal trauma may occur. The signs and symptoms of isolated splenic injury include tenderness in the left upper quadrant of the abdomen. Attention must be directed towards the lower lateral left ribs; focal tenderness over ribs 9 through 11 in that region should raise suspicion of possible splenic injury. Approximately 20% of cases of rib fracture can be demonstrated on radiographs. Patients may have referred pain to the left shoulder (Kehr sign) particularly when placed in the Trendelenburg position with palpation of the upper abdomen. The spleen itself is rarely palpable but when a left upper quadrant mass is palpable, it likely represents a contained hematoma or a subcapsular hematoma (Ballance sign). Depending on the severity of the injury, patients may have no hemodynamic instability or may be in frank hypovolemic shock. The grading system for splenic trauma is summarized in Table 73-7.

The diagnostic studies associated with splenic rupture would potentially include a decrease in hematocrit and hemoglobin although initial assessment before volume resuscitation may show normal levels. After a short period of time there is often a leukocytosis in the range of 15,000 to 20,000. Plain abdominal x-ray films, in addition to possibly showing left rib fractures, may show displacement or a corrugated appearance along the greater curvature of the stomach due to a hematoma infiltrating the gastrosplenic ligament (Fig. 73-6). Peritoneal lavage will reveal the presence of blood in the abdomen. The most important current tool for diagnosis particularly in patients who are hemodynamic stable enough to be managed conservatively is the CT scan. Contrast CT scan will show the splenic contour and will also show the amount of extrasplenic blood (Fig. 73-7).³⁰

Overall blunt injuries comprise the majority of splenic trauma, but the spleen is susceptible to penetrating trauma in the retroperitoneum, lower thoracic penetrating trauma, or upper abdominal penetrating trauma. A 15-year state review of splenic trauma in Pennsylvania reported 10,652 (92%) blunt injuries and 893 (8%) penetrating.²⁹ The management and diagnosis of penetrating injuries trauma of the thorax and upper abdomen are less of a diagnostic dilemma as a majority of these patients undergo abdominal exploration because of associated injuries. In some series, there are additional injuries in 90% to 100% of patients with penetrating trauma to the spleen and 40% to 60% associated injuries in cases of blunt trauma.

Management of splenic injuries historically has been a laparotomy with splenectomy. Since Christo introduced the ability to do either partial splenectomy or splenorrhaphy, there has been an increased trend with surgical procedures to try to repair or preserve part, if not all, of the spleen. The current trend in management is a nonoperative approach with observation in serial CT scans.³¹ The presence of peritonitis, associated injuries requiring surgery, overall injury severity, evidence of hypovolemic shock with ongoing bleeding, and the patient’s age are the primary factors that are taken into consideration while deciding on nonoperative versus operative management of blunt splenic injuries.²⁹ If patients have diffuse peritonitis or if patients have hypotension related to hypovolemic shock, urgent laparotomy is indicated (Fig. 73-8). There have been increasing reports of splenectomy successfully performed laparoscopically for blunt splenic trauma³²; however, a minimally invasive approach is typically used very selectively in this setting, given the frequent hemodynamic instability and concurrent injuries that may be better addressed via laparotomy. For patients who are hemodynamically stable and do not have other injuries that require surgical management, the recommendation is to attempt nonoperative observation of these patients.

The standard nonoperative management protocol would include very close observation in an intensive care unit or a similar monitored environment. Patients would have serial abdominal examinations as well as serial hemoglobin and hematocrit assessments. Any change in status in which patients remain otherwise relatively stable would be evaluated with a follow-up CT scan to see if there is progressive or ongoing bleeding demonstrated by increased hemoperitoneum or expansion of splenic hematoma. A recent report noted that routine follow-up CT scans did not alter management in patients treated nonoperatively.³³ Only patients with changes in hemodynamic parameters had a change in management. With this conservative management, the majority of patients would avoid laparotomy for isolated splenic blunt trauma.³⁴ If patients are older, have associated injuries, or have ongoing blood loss, a laparotomy is appropriate for blunt splenic trauma.^28,35 Again, the nature of the splenic injury is graded relative to the degree of damage to the splenic parenchyma and the proximity to the splenic hilum and major blood vessels (Table 73-7). The principles of operative management would include stopping ongoing hemorrhage while preserving the maximal amount of viable splenic parenchyma. Nonviable or devascularized tissue must be debrided.³⁶ Partial splenectomy has been popularized on the basis of the concept of segmental blood supply via the trabecular arteries. A variety of approaches can be taken to more minor peripheral splenic trauma including primary repair or mesh repair (Fig. 73-9). Utilization of multiple material that are available for hemostasis including microfibrillar collagen, thrombins of gelfoam, or fibrin glue sealants have been utilized to obtain control of splenic hemorrhage. The argon beam coagulator is a very useful instrument for capsular tear or evulsions. Of note, all of these techniques that have been applied to patients with blunt trauma can be similarly applied to patients who have inadvertent trauma to the spleen during operations for other reasons (surgeries involving dissection of the splenic flexure of the colon or the left kidney, adrenal gland, or stomach).

Over the past decade, this trend towards non-surgical management has expanded, with increasing success rates noted with conservative management. A recent study of more than 625 patients with blunt trauma over the past decade compared with the prior decade showed that there was an increase in initial nonoperative management from 61% to 85%.³⁷ The success rate of nonoperative management increased as well from 77% to 96% and the splenic salvage rate from 57% to 88%.³⁷ This may be partly due to a decreased distribution of more severe splenic injuries and partly the result of an increasing trend toward the use of embolization of splenic arteries as part of the nonoperative management of blunt trauma. A recent systematic review of 16,490 patients with blunt splenic trauma reported that for severe splenic trauma, nonoperative management was associated with a decreased mortality rate as compared with operative management (4.8% vs. 13.5%).³⁸ However, the higher mortality rate observed in the group managed operatively appeared could be explained by the presence of other concurrent injuries in that group. The authors concluded that, while nonoperative management remains the recommended approach by the American Association for the Surgery of Trauma for grade I and II injuries, the data for managing more severe splenic injuries are very heterogeneous with multiple potential confounders, making it more difficult to interpret.

Since its introduction in the early 1992 as a potential maneuver to improve the nonoperative management of blunt splenic injury, embolization with either coils or gelfoam of either proximal or distal splenic vessels has had increased utilization,³⁹ extending into the management of selected grade 3 or 4 injuries. In the study comparing the outcome of blunt trauma over the past two decades, the use of embolization increased from 2.7% to 22.6%.³⁷ The majority of studies provide similar data that the overall success rate for nonoperative management with splenic artery embolization is improved and could decrease the use of blood products.⁴⁰ There have been some recent studies stating that this may be overutilized and a report of a failure rate of 27% in patients with embolization failed and needed surgical exploration.⁴¹ Again, these comparative studies are not matched in terms of severity of injury or even the techniques used for the splenic artery embolization.

One corollary with the nonoperative management of blunt splenic trauma is the risk of delayed rupture. Standard guidelines of conservative management are that patients should have stable hemoglobin for 36 to 48 hours and have resolution of abdominal pain prior to discharge. The delayed rupture rate in a large series of more than 1,900 patients showed that 27 patients were readmitted for splenectomy within 180 days of discharge,⁴² a delayed rupture rate of 1.4%. The median time from injury to readmission for splenectomy was 8 days with the range of 3 to 146 days. Similar results were obtained in an institutional study of 450 patients with nonoperative management of blunt splenic injury. In this group, 4% failed with eventual splenectomy due to delayed rupture.⁴³ Both studies stress that with the increased use of nonoperative management, the potential risks of delayed rupture require very specific discharge instructions to patients regarding reonset of acute abdominal pain with other signs and symptoms of hypotension requiring emergent transportation to the nearest emergency room or hospital facility.

Another area of splenic trauma is atraumatic splenic rupture. This can be considered more spontaneous rupture and it occurs primarily with enlargement of the spleen with malignant disorders either primary or secondary metastases, infectious disease, or inflammatory diseases, or technical disorders such as pregnancy or peripartum rupture. In a large series of more than 900 patients with atraumatic spontaneous rupture of the spleen, only 6.4% had no pathologic or mechanical causes that were identified.⁴⁴

Autoimmune/Erythrocyte Disorders

There are two categories of disease in which abnormalities do not originate in terms of the histology, pathology, or size of the spleen but rather are due to either autoimmune phenomenon or intrinsic diseases within circulating cells that lead to their destruction. The most common and obvious example of this is ITP in which antibodies to platelet antigens lead to destruction of platelets and thrombocytopenia with the spleen being the primary source of platelet elimination. Related diseases affecting erythrocytes and neutrophils with specific antibodies and splenic elimination occur to lesser degrees.

A second category of disease is not an autoimmune phenomenon but rather an intrinsic cellular defect that leads to a shortened half-life of this specific blood cell within the circulation primarily to elimination within the spleen. As discussed in the physiology section given earlier, a normal role of the spleen is to eliminate senescent erythrocytes and the anatomic structures of splenic circulation are well suited to that task. If erythrocytes are altered in terms of their structure, this may lead to more rapid elimination. In other diseases, genetic differences in the hemoglobin may result in splenic changes particularly in the setting of hypoxia that occurs within the splenic sinusoids. The most obvious example of this would be sickle cell anemia. A final example is an alteration in the cellular adhesion molecule that leads to increased interaction and thrombocytopenia in the Wiskott–Aldrich syndrome.

Immune Thrombocytopenic Purpura

ITP is often a diagnosis of exclusion once all other causes such as drug-induced thrombocytopenia or evidence of bone marrow failure are eliminated.⁴⁵ ITP is a disease characterized by autoimmune destruction of platelets with clinical manifestations of thrombocytopenia manifest by susceptibility to easy or excess bleeding.⁴⁶ ITP may be classified into an acute form and a chronic form. Acute ITP generally occurs in children younger than 8 years following an upper respiratory viral illness. The majority of children with acute ITP will have spontaneous remissions, whereas only a small minority of adults who develop ITP have remission and most go on to develop chronic ITP. This disease is usually self-limited and requires surgical intervention only in the case of intracranial bleeding. Chronic ITP accounts for the vast majority of cases considered for splenectomy. Similar to autoimmune hemolytic anemia, this disease may be idiopathic or may be secondary to a lymphoproliferative disorder, connective tissue disorder such as systemic lupus erythematosus, or drug or bacterial exposure. The average age at diagnosis is in the fourth decade of life and it affects women more commonly than men. As HIV was identified in the mid-1980s, it was noted that patients with acquired immunodeficiency syndrome (AIDS) were developing disease virtually identical to ITP.⁴⁷ AIDS patients with newly diagnosed ITP and risk factors for HIV should undergo screening.

6 The pathophysiology of ITP is development of an IgG antibody to a platelet antigen. This is felt to be most commonly directed against the fibrinogen receptor (glycoprotein IIb/IIIa and IR/IX).⁴⁸ The spleen plays a predominant role in this disease as it may be the site of initial antibody production.⁴⁹ It is almost certainly the site of continued antibody production, and in the majority of patients the spleen is the primary site of platelet destruction. Since the targeted antigen is an intravascular cell, and since the spleen stores large numbers of platelets, it is felt that the initial reaction to the platelet cell antigen may occur in the spleen. Studies on antibody levels have indicated that overall IgG production in spleens from patients with ITP is markedly increased over individuals with normal spleens. Similarly, following splenectomy the amount of IgG antibody is somewhat decreased. The spleen is also the predominant site of platelet destruction. As noted earlier, the macrophages located in the cords of Billroth have receptors for the Fc portion of the IgG and will bind and phagocytize the antibody-coated platelets. A second more recently described component of the pathophysiology is an inappropriately decreased level of production of thrombopoietin for that level of thrombocytopenia. Cloning of the thrombopoietin receptor or the megakaryocytes has led to several new agents that can alter this aspect of the pathophysiology of ITP.^50,51

To be considered to have ITP, the platelet count has to at least be <100,000, but typically patients do not become symptomatic unless platelet counts are <50,000. Platelet counts in this disorder may drop to very low levels, well below 10,000 on occasion. Assays are now available to identify the IgG antiglobulin on the platelet surface verifying the disease, but over one third of the patients have no clear identification of antiplatelet antibodies. Bone marrow analysis shows an increased megakaryocytes production as compensatory mechanism to the thrombocytopenia. In this disorder, there is often no splenomegaly and the spleen may be somewhat smaller than typical. Only 2% of patients with ITP have palpable spleens. For this reason, there is virtually no leukopenia or anemia associated with ITP due to hypersplenism. There may be anemia secondary to chronic blood loss. The risk of a fatal hemorrhage in patients with ITP overall is 0.0162 and 0.0389 cases/patient year and predicted 5-year mortality rates are 2.2% for patients <40 years of age and 47.8% for patients older than 60 years.⁵²

The treatment of ITP includes standard measures to treat any ongoing bleeding, medical therapies designed to increase platelet count, and splenectomy. First-line medical therapy options include platelet transfusion, corticosteroids, gamma-immunoglobulin, and the recently approved Rho (d) immunoglobulin.⁵³ Platelet transfusions should be discouraged unless patients are actively bleeding as platelets will become rapidly coated with IgG and will be sequestered and destroyed in the spleen. High-dose corticosteroids produce an initial response in the majority of patients but this is unfortunately not sustained. Approximately 75% of the patients will have an increase in platelet count that is significant within 24 hours of starting high-dose steroids.⁵⁴ However, only 15% to 25% of patients will have a sustained remission with chronic ITP following steroid therapy. A second aspect of initial medical treatment for chronic ITP has been administration of intravenous IgG immunoglobulin. This treatment takes only between 3 and 5 days to show an effect and generally does not put patients into complete remission. The mechanism of action of immune gamma globulin is felt to be saturation of the Fc receptors on the splenic macrophages.⁵⁵ The administered gamma globulin may coat red cells and they may provide a competitive interference such that platelet destruction is decreased. A new available drug is the recently approved Rho (d) immunoglobulin that specifically targets the Fc receptors.

In patients who have not achieved a sustained remission with medical therapy, which is the majority of patient with chronic ITP, an elective splenectomy is recommended. A large series analyzed 135 case series between 1966 and 2004⁵⁶ and reported results in terms of normalization of platelet counts, predictive features evaluating which patients would likely achieve complete response following splenectomy, and reported complications of the procedure including morbidity and mortality (Table 73-8). Among the case series analyzed reporting only on adults (1,731 patients), the complete response upon splenectomy was noted to be 66% (median follow-up of 29 months). Response rates tended to be higher among children, and when cases series evaluating adults and children (2,463 patients) were included in analysis, the complete response rate was noted to be 72% (median follow-up 23 months).⁵⁶ Among cases series that included a multivariate analyses in the systematic review, age (younger) was associated with an increased likelihood of response to splenectomy. Response to prior medical therapy was not found as an independent predictor in those studies, and site of platelet sequestration also was variably reported among the case series evaluated with regard to its predictive role on response to splenectomy. A proportion of patients with initial response to splenectomy (15% to 20%) develops relapse with long-term follow-up. One cause for a failed splenectomy for ITP would be residual splenic tissue most commonly in the form of a missed accessory spleen but also in the form of splenosis.¹⁷ While earlier reports expressed concerns of laparoscopy splenectomy demonstrating a high number of failure rates secondary to residual splenic tissue,⁵⁷ more recent studies suggest similar efficacy of the laparoscopic and open approaches in the management of patients with ITP.⁵⁸

Several new agents have recently been developed or been applied to the treatment of ITP. There were initially several studies with rituximab, which is a chimeric humanized monoclonal antibody directing CD20 against B cells.^59–61 It was primarily developed to treat lymphoma but it has been used in autoimmune disorders and has been tried in phase 2 studies for chronic splenectomy failure ITP. Response rates have been somewhat sporadic between 25% and 50%. Two new drugs binding the thrombopoietin receptor on megakaryocytes have recently been approved for second-line treatment of chronic ITP: the recombinant peptide romiplostim and eltrombopag, a thrombopoeitin nonpeptide mimetic.⁶² Again, it was realized that there is decreased thrombopoietin production for the degree of thrombocytopenia seen in ITP. Romiplostim, which is a fusion protein agonist for thrombopoietin receptor administered by subcutaneous injection, led to response rates of 49% versus 2% for placebo with an overall clinical response rate of 83%.^48,63 An oral nonpeptide thrombopoietin receptor agonist, eltrombopag, showed response rates of 79% versus 28% in a placebo controlled trial.⁶⁴ Several other newer agents including AKR-501 (thrombopoietin nonpeptide mimetic), and fostamatinib disodium, a spleen tyrosine kinase inhibitor are under clinical investigation.⁶² The role of these and other agents in the armamentaria against treatment of ITP will only likely increase in scope in the future. Future studies will define the role of these new compounds and may decrease the incidence and need for splenectomy.

Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenia purpura, or Moschcowitz syndrome, is a poorly understood much more virulent syndrome than ITP in which thrombocytopenic purpura is only one manifestation. This disease is characterized by widespread occlusion of arterials and capillaries by hyalin membranes that are composed of a combination of platelets and fibrinogen. The classic pentad of symptoms reflects various organ injuries with this microvascular process. This includes thrombocytopenic purpura, with microvascular disease in the skin, neurologic manifestations due to microvascular disease in the central nervous system, renal failure or hematuria due to microvascular disease in the kidney, microvascular hemolytic anemia due to destruction of red cells traveling to damaged small vessels, and fever. The precise etiology is unknown but may be related to an autoimmune response to small vessel endothelial cell antigen.

The therapeutic options for this disease include administration of fresh frozen plasma and/or plasmapheresis, high-dose corticosteroids, and antiplatelet drugs.⁶⁵ The benefits seen with plasmapheresis would indicate that there is a toxic substance that is contributing to the etiology of this disorder circulating in the plasma, whereas the benefit of administration of fresh frozen plasma would indicate lack of some necessary substance that has yet to be identified. High-dose corticosteroids also lead to some benefit. Aspirin and dipyridamole block platelet agglutination. A combination of these therapies now leads to a significant improvement of symptoms in 70% of patients. For patients failing to respond or patients who relapse, a splenectomy has been performed with some success.^66,67 The majority of the long-term survivors with thrombotic thombocytopenic purpura (TTP) have undergone splenectomy, implying that this organ has some major role in the pathophysiology of this disease.⁶⁸ The precise mechanism of splenic contribution is unclear. Mortality rates in the past have been as high as 90% to 95% for this disorder but are improving with aggressive treatment plans and a better understanding and diagnosis of this disorder.

Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia or acquired hemolytic anemia results from antibodies produced to red cell membrane proteins that lead to red cell destruction. This disease is more common in women than in men with the ratio of 2:1, and it typically presents after the age of 50 years. Patients present with acute symptoms consisting of anemia, jaundice, and occasional fever. The spleen is enlarged in approximately half of the patients. Laboratory diagnosis shows a positive direct Coomb test indicating antibody coating the erythrocytes. There is also significant reticulocytosis and increased indirect bilirubin in the serum.

The disease is considered to be either idiopathic in 40% to 50% of the cases in which no identified drug or infectious cause is identified or secondary to infection or drug. Of the secondary cases, the most common infections are mycoplasmal pneumonia, viral infections, infectious mononucleosis, and AIDS, and it can also occur with neoplastic diseases such as leukemia and lymphoma. The major drugs that cause secondary autoimmune hemolytic anemia are penicillin, quinidine, hydralazine, and methyldopa.

A second way that autoimmune hemolytic anemia is categorized is by either cold antibodies or warm antibodies. Warm antibodies are predominantly IgG, whereas cold antibodies are predominantly IgM. This distinction is quite important when considering splenectomy as a treatment. The spleen contains macrophages that bind the Fc portion of IgG. For this reason, in patients with warm antibody hemolytic anemia, the spleen is the primary source of destruction of the red cells by the red pulp macrophages. However, since the spleen does not contain receptors to bind IgM or the cold antibodies, there is no destruction of the red cells in this form of hemolytic anemia. Rather, IgM either causes complement fixation with destruction of red cells in the liver predominantly, or there is agglutination of red cells in peripheral circulation such as the distal extremities leading to peripheral red cell destruction with clinical manifestations similar to Raynaud phenomenon. Splenectomy for patients with cold antibody or IgM hemolytic anemia is not effective.

The treatment of autoimmune hemolytic anemia initially consists of supportive therapy such as blood transfusions. For patients who have disease secondary to an acute infection such as a mycoplasm pneumonia, the disease may be self-limited. For drug-induced hemolytic anemia, the offending agent is removed as quickly as possible. The initial form of treatment is typically high-dose corticosteroids that cause a beneficial response in 75% of the patients. If patients again have drug-induced disease and the offending agent is removed or the acute infection resolves, this may lead to long-term resolution. In idiopathic autoimmune hemolytic anemia, only 25% of patients have sustained remission from steroid use. In patients who have relapse after steroid therapy or who are ineligible for steroid therapy and have warm antibodies, a splenectomy has a high likelihood of benefit. Eighty percent of patients show a good response in correcting the anemia by splenectomy.⁶⁹ This is felt to be almost certainly related to removal of the site of destruction of the erythrocytes but also may be due to a decrease in production of source of antibodies.

Autoimmune Neutropenia (Felty Syndrome)

Approximately 1% of patients with chronic rheumatoid arthritis will develop splenomegaly and neutropenia. This triad of rheumatoid arthritis, neutropenia, and splenomegaly is known as Felty syndrome.⁷⁰ High levels of IgG have been identified on the surface of neutrophils with evidence of increased production of granulocytes in the bone marrow. Pathologic analysis of spleens removed in patients with Felty syndrome show a significant but proportional increase in the white pulp of the spleen as opposed to other conditions of splenomegaly.⁷¹ Microscopically, there is evidence of excess accumulation of neutrophils in both the T cell zone and the white pulp, as well as the cords and sinuses of the red pulp.

Patients with this disease will have recurrent infections due to neutropenia as well as dysfunction of the available neutrophils that are coated with antineutrophil IgG. Recurrent infections, as well as chronic leg ulcers, are the predominant symptoms. Symptomatic patients should undergo splenectomy and the vast majority of patients will have resolution of their neutropenia within 2 to 3 days.⁷² Even patients who do not have a significant increase in neutrophil count should get some benefit because of improved neutrophil function.⁷³

Hereditary Spherocytosis

Hereditary spherocytosis, also known as congenital hemolytic jaundice or familial hemolytic anemia, is an autosomal dominant disease that is the most common of the congenital hemolytic anemias affecting 1 in 5,000 individuals.⁷⁴ There are a variety of genetic defects in this syndrome that primarily affect spectrin and ankyrin that alter the binding of the cytoskeleton to the erythrocyte cellular membrane causing decreased cellular plasticity with membrane loss.⁷⁵ The normal shape of the erythrocyte is changed from the biconcave disc into a sphere and the decreased membrane-to-volume cell ratio causes a lack of deformability that impacts the passage of erythrocytes through channels of the splenic red pulp. Because of this delay in cell transit, there is ATP deprivation resulting in increased cellular destruction. The condition is more frequent in Caucasians and in African Americans and is usually noted in the childhood or adolescent ages. Since it is an autosomal dominant inheritance, patients may be screened and diagnosed at quite an early age.

The diagnosis is primarily made by evaluation of the red cell smear showing a large number of spherocytes. Spherocytes may also appear during autoimmune hemolytic anemias but in hereditary spherocytosis the Coombs test is negative and an osmotic fragility test may be performed which is diagnostic. Also, contributing to the diagnosis is a positive family history.

Patients with hereditary spherocytosis have mild to moderate anemia, splenomegaly, and jaundice. The patients may have intermittent flares of disease that cause significant increased rates of hemolysis causing jaundice. Between 30% and 60% of patients have been reported to have pigmented gallstones due to the breakdown of hemoglobin.⁷⁴

The treatment for hereditary spherocytosis is splenectomy that is indicated in virtually all patients.⁷⁶ This treatment does not remove the spherocytes but it relieves all symptoms.⁷⁷ The major question involving management of these patients is the timing of splenectomy. Because of the increased incidence of overwhelming postsplenectomy sepsis in very young children, it is usually recommended that patients wait until after the age of at least 4 if not 6 years prior to splenectomy. For younger patients who are very symptomatic and require splenectomy, partial splenectomies have been reported to be beneficial in relieving the abdominal symptoms as well as the anemia and may be a useful alternative procedure until patients reach an age in which total splenectomy is safer.⁷⁸ Patients with partial splenectomies had regrowth of tissue but with short term did not have recurrent anemia.⁶⁹ Patients should be assessed at the time of scheduling a splenectomy for the presence of gallstones and a laparoscopic cholecystectomy should be performed if stones are identified.

Hereditary Elliptocytosis

Hereditary elliptocytosis is a disease that is related to hereditary spherocytosis although not as severe. For patients who are symptomatic, virtually all of the same comments regarding pathophysiology and treatment can be made about hereditary elliptocytosis as for hereditary spherocytosis. This disease is also inherited in an autosomal dominant pattern and the defect is felt to be present in spectrin. The predominant abnormality changes spectrin such that it exists as a dimer instead of tetramer that is the normal structure. This change leads to an alteration in membrane plasticity that creates cells that are more elliptically shaped instead of a biconcave disc.

The signs and symptoms caused in this disease are much more mild than hereditary spherocytosis in that only 10% of patients have clinical manifestations of anemia, splenomegaly, and in some cases jaundice. The treatment recommendation for symptomatic patients is splenectomy again, which may be performed with laparoscopic techniques and also cholecystectomy if gallstones are present.

Hereditary Nonspherocytic Hemolytic Anemia

There is a heterogeneous group of rare hemolytic anemias caused by inherited defects primarily enzymes involved in glycolysis. It is felt that these genetic defects may decrease cellular energy production leading to increased red cell destruction as these cells pass through the relatively hypoxic environment of the red pulp of the spleen. The most common subtypes in this group of hemolytic anemias are pyruvate kinase deficiency and glucose 6-phosphate dehydrogenase (G6PD) deficiency. Patients present with anemia, jaundice, increased reticulocytes, and possibly cholelithiasis. The diagnosis can be facilitated in that the shape of the cell does not show typically spherocytes and there is normal osmotic fragility.

The primary treatment for these diseases is blood transfusion. In G6PD deficiency, splenectomy is not felt to be beneficial whereas it may reverse some of the symptoms associated with pyruvate kinase deficiency.

Thalassemia

Thalassemia is an autosomal dominant disease with a variety of structural defects in one of the globin chains. The disease is categorized as these are alpha, beta, gamma, or delta thalassemia, depending on which of the globin chains is defective. The vast majority of patients in North America have beta thalassemia. Thalassemia major, otherwise known as Mediterranean anemia or Cooley anemia, is a homozygous expression of this genetic defect. Thalassemia minor is a heterozygous expression and these patients are only mildly symptomatic and are carriers for the more severe form of the disease.

The pathophysiology of thalassemia major or beta thalassemia is the lack of production of normal beta-chain hemoglobin leading to a surplus of alpha-chain hemoglobin in adult patients. These excess globin chains precipitate in the cytoplasm and attach to the inner surfaces of cytoplasmic membrane leading to poor passage of these cells through the splenic sinusoids. This intracellular inclusion then leads to increased destruction and over time causes significant splenomegaly due to this increased clearance of red cells.

The diagnosis is made by identifying microcytic hypochromic anemia with target cells and an increase in reticulocytes on the peripheral smear. Protein electrophoresis will show very low levels of hemoglobin A with predominant amounts of the fetal hemoglobin or hemoglobin F. The clinical symptom of alpha-thalassemia major is severe anemia within the first year of life. Decreased growth rate, enlargement of the head, splenomegaly, and hepatomegaly are the typical clinical findings.⁷⁹

The primary treatment for thalassemia major is frequent transfusions combined with iron chelation therapy. Some patients may develop significant splenomegaly due to overload or hypertrophy from excess trapping of red cells.⁸⁰ Patients may be referred for splenectomy for symptomatic splenomegaly or for patients with massive and frequent transfusion requirements. One report suggested that episodes of transfusion are decreased from 18 per year down to 4 per year after splenectomy. In general, if there are symptoms of massive splenomegaly, these will be resolved with splenectomy as well. As with other hematologic disorders in children, there has been a recent trend toward partial splenectomy particularly in children younger than 4 to 5 years.⁸¹ This will result in symptomatic improvement in between 1 and 2 years with recurrent disease due to hypertrophy of the residual splenic remnant.⁸²

Although splenectomy may be beneficial in terms of the transfusion requirements and local symptoms, the typical mode of death with this disease is myocardial failure due to hemosiderin accumulation. Splenectomy does not alter this cardiac problem to any great extent. In fact, recent data suggest that splenectomy in thalassemia patients increases vascular complications.

Sickle Cell Anemia

Sickle cell anemia is a hereditary hemolytic anemia that is due to a genetic alteration of a single amino acid substitution in the beta chain. This results in a change from glutamic acid to valine in the sixth amino acid position of the beta chain of hemoglobin molecule. Because of this substitution, patients who are homozygous for sickle cell defect have a characteristic stiffening or sickling of the red blood cells when they become hypoxic.⁸³ This change in red cell shape leads to blockage in hypoxic areas such as the red pulp of the spleen. There can occasionally be sequestration crises in which a portion of the blood volume gets actively trapped or sequestered to the spleen during the sickle cell crisis. This pattern of red cell shape change in relatively hypoxic areas can lead to tissue infarction with bone pain, hematuria, abdominal pain, and priapism.

The incidence of this disease, which almost exclusively occurs in the black population, is approximately 0.5% for homozygous disease, with approximately 8% of African Americans being carriers for the sickle cell trait. Patients who have a combination of a sickle cell allele as well as a beta thalassemia allele manifest a similar disease process.

The clinical signs of the disease usually present during the second 6 months of life as in early infancy the patient is asymptomatic due to the presence of fetal hemoglobin. The patients may have acute crises with abdominal pain and bone pain in conjunction with significant anemia. During acute crises of splenic sequestration, there may be massive enlargement of the spleen with an urgent decompressive splenectomy required. Patients who do not need splenectomy for splenic sequestration may be followed as this disease goes through a natural progression of ischemic necrosis of large areas of the spleen with eventual hyposplenism with a shrunken organ by early adolescence. Splenectomy is reserved for the very young patients who have massive splenomegaly in sequestration crises early in life.

Wiskott–Aldrich Syndrome

Wiskott–Aldrich syndrome is an X-linked disease characterized by thrombocytopenia, combined B- and T-cell deficiency, eczema, and a propensity to develop other malignancies. The genetic defect in this disease is felt to be related to an abnormal adhesion molecule affecting immune cell interaction as well as platelet adhesion. Thrombocytopenia is the major problem with this rare disease and most patients present with manifestations of poor clotting, bloody diarrhea, epistaxis, and petechiae at a young age. The platelet counts typically range between 20,000 and 40,000 and the platelets that are present are dysfunctional being small sized, 25% to 50% of normal platelet volume. In this disease, the spleen sequesters platelets and partially degrades them releasing “microplatelets” back into the circulation.⁸⁴

Splenectomy in the Wiskott–Aldrich syndrome was initially avoided as there was a very problematic postoperative course characterized by severe and fatal infections due to the underlying immunodeficiency combined with the potential for overwhelming postsplenectomy infection. However, splenectomy does increase the number, size, and function of platelets and can lead to amelioration of the bleeding problems in very symptomatic patients.⁸⁴ The combination of splenectomy with antibiotic suppression particularly in younger patients may be beneficial. The optimal treatment of Wiskott–Aldrich syndrome is an human leukocyte antigen (HLA) match sibling bone marrow transplantation.⁸⁵ However, splenectomy with antibiotics results in better survival than unmatched bone marrow transplantation. Patients who do not undergo bone marrow transplantation or splenectomy typically do not survive past the age of 5 years. The pathology of spleens removed for Wiskott–Aldrich syndrome shows a near complete depletion of white pump supporting the clinical immune deficiency seen in this syndrome.⁸⁶

Hypersplenisim

7 Hypersplenism is a physical enlargement of the spleen that can be broadly categorized as the neoplastic disorders, hematopoietic disorders of the bone marrow, and metabolic or storage disorders. In neoplastic disorders, the spleen is infiltrative and large typically by leukemic or lymphoma cells. This often happens in the mid or late course of a person’s disease but can be associated with isolated splenomegaly in which the splenectomy is performed not only to treat hypersplenism, but also to make the definitive diagnosis (see Diagnostic Splenectomy section below). Hypersplenism can be associated with diseases of hematopoiesis related to myeloid metaplasia in which the bone marrow is infiltrated with fibrotic material and the spleen becomes a site of secondary non–bone marrow hematopoiesis. Enlargement can lead to symptoms of hypersplenism due to the massive size of the spleen and often the benefits of extramedullary hematopoiesis are outweighed by the sites of circulating blood cell destruction in this enlarged spleen. Secondary hyperplenism can also occur when there is deposition of lipid within the spleen such as in Gaucher disease leading to enlargement that can cause pancytopenia. Each of these categories of secondary hypersplenism is associated with pancytopenia and mass effect of the spleen causing early satiety and weight loss. These disorders typically lead to spleen size more than 1,500 g and can produce spleens that essentially fill the entire left side of the abdomen.

Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common of all chronic leukemias. It predominantly affects males more than females with 2:1 predominance and has a peak incidence in the sixth decade of life or older. This indolent disease presents with fatigue, lymphadenopathy, hepatosplenomegaly, and eventually anemia and thrombocytopenia. The disease progression may occur over a 5- to 10-year period.

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