Surgical Diseases Of the Spleen KSMU

8/3/2019 Surgical Diseases Of the Spleen KSMU

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THE SPLEEN

ANATOMYEmbryonic development of the spleen begins in the fifth week of gestation as a small clusterof mesenchymal cells in the dorsal mesogastrium between the stomach and pancreas.Mesenchymal remnants that do not fuse with the main splenic mass account for the highincidence (15%30%) of accessory spleens in adjacent tissues.

The spleen is the second largest organ of the reticuloendothelial system. It is located in theposterior left upper quadrant of the abdomen where its relationships to the diaphragm,stomach, pancreas, left kidney, and splenic flexure of the colon are maintained by suspensoryligaments. The splenophrenic, splenorenal, and splenocolic ligaments are usually relativelyavascular, except in patients with portal hypertension, and their transection allows the spleento be displaced medially and anteriorly. The gastrosplenic ligament, which extends from thegreater curvature of the body and fundus of the stomach to the spleen, contains the shortgastric arteries and veins. Located in the most medial aspect of the splenorenal ligament andattached to the spleen at the hilum, the splenic pedicle contains the splenic artery and vein,lymphatic structures, and often the tail of the pancreas .

The arterial supply to the spleen is derived from the celiac artery from both the splenic arteryand the short gastric arteries, which usually arise as branches of the gastroepiploic or the

splenic arteries . The splenic vein is formed by a coalescence of polar veins in the splenichilum and courses with the splenic artery along the dorsal surface of the pancreas to enterthe portal system.

The normal adult spleen is a slightly concave, solid, dark red organ that measuresapproximately 3 8 14 cm., weighs between 100 and 175 gm., and frequently has fetallobulations on its anterior edge. A thin peritoneal capsule encloses the deeper organ pulp andeasily strips from it. In elderly individuals or in those with prior splenic injury, irradiation, orrecurrent infarction, the splenic capsule may become firm and thickly scarred (sugarcoated) and adherent to the diaphragm.A trabecular connective tissue framework extends into the splenic pulp from the internalcapsular surface to subdivide the organ into small communicating compartments. Afterentering the spleen at the hilum, arterial vessels branch into the trabeculae to enter the pulp.Veins and lymphatics draining the pulp also pass in the trabeculae to leave the spleen at thehilum. The splenic pulp is conventionally divided into three areas: red pulp, white pulp, and aninterfacing marginal zone. The red pulp, so designated due to its gross appearance from thepresence of blood, is composed almost entirely of large, branching, thin-walled blood vessels,called splenic sinuses or sinusoids, and thin plates or cords of cellular tissue lying between thesinuses to form splenic cords. Within this cordal meshwork, erythrocytes, platelets, and somegranulocytes are crowded with macrophages and plasma cells, with macrophages often beingthe predominant cells. Lying within and surrounded by the red pulp are small gray-whitezones of lymphatic tissue consisting of lymphocytes, plasma cells, and macrophages, whichconstitute the white pulp. The white pulp forms periarterial lymphatic sheaths and lymphaticnodules, which, like those of lymph nodes, may contain germinal centers. The marginal zone

constitutes the interface between the red and white pulp and is an ill-defined vascular spacewhere many arterial vessels terminate.Controversy has surrounded the exact nature of the splenic microcirculation for 300 years.Billroth is credited with the open circulation theory, in which either arterioles empty blooddirectly into tissue spaces or arterial capillaries open into pulp cords, with blood cells thenpassing through pores in the walls of splenic sinusoids to enter the venous circulation. In theclosed circulation theory, splenic blood follows an endothelialized pathway throughout to flowdirectly into sinusoids. Studies in rabbits using plastic microspheres too large to pass throughpores of the venous sinuses confirm the unique open splenic microcirculation. Ninety percentof splenic arterial flow enters the open circulation of the red pulp, with only 10% of the bloodin arterial capillaries emptying directly into venous sinuses. Blood cells and particles such asparticulate antigens must circulate through the meshwork of splenic cords before squeezing

through 0.5 to 2.5 mm. pores between endothelial cells of the sinuses to enter the venouscirculation.

FUNCTION


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During early fetal development, the spleen produces red and white blood cells. By the fifthmonth of gestation, the spleen and other extramedullary sites of blood cell production nolonger have hematopoietic function but retain the capability throughout life. As a result of asingular microcirculation, the spleen is a sophisticated filter having both blood cell monitoringand management functions and important immune functions. When the spleen is removed,these functions are lost.Normal red cells usually traverse the splenic circulation but may undergo repair by havingsurface abnormalities such as pits or spurs removed. Reticulocytes pass through the spleen

more slowly than mature red cells and lose nuclear remnants and excess membrane beforeentering the circulation as mature cells. In reducing the membrane surface area, the spleenconverts the red cell from a target appearance to a biconcave disc. The spleen also removeshigh-molecular-weight surface protein, Howell-Jolly bodies (nuclear remnant), Heinz bodies(denatured hemoglobin), Pappenheimer bodies (iron granules), and spur cells. These cleanedred cells, if they have the deformability to pass through the splenic circulation, re-enter thebloodstream. Aged red cells (120 days) that have lost enzymatic activity and membraneplasticity are trapped and destroyed in the spleen

The normal filtering function of the spleen also enables it to remove abnormal blood cells.Morphologically abnormal erythrocytes, such as the spherocytes of hereditary spherocytosis,fixed sickled cells, and rigid hemoglobin C cells, are trapped by the splenic filter. Blood cells

coated with IgG are destroyed by the splenic monocytes, which have surface receptors for theFc fragment of the IgG coating the cells. Because the spleen removes cells coated with IgG orIgM, it is the site of destruction in diseases such as autoimmune hemolytic anemia (AIHA),immune thrombocytopenic purpura, and probably Felty's syndrome. Parasites withintraerythrocytic habitation, such as malaria, can be pitted from the red cell by the spleen. 8Red cells that are unable to deform to pass into the splenic sinuses are eventually destroyedby the histiocytes/macrophages of the red pulp.In addition to blood cell morphology and surface characteristics, rate of blood flow throughthe splenic microcirculation and alterations of splenic pulp pressure affect the filteringfunction of the spleen. For example, patients with splenic vein thrombosis have slow red cellpassage through the splenic microcirculation due to elevated portal-splenic pulp pressure,with resultant increased red cell sequestration and destruction.

The spleen is involved in specific and nonspecific immune responses. Properdin and tuftsin,which are synthesized in the spleen, are opsonins. Tuftsin binds to granulocytes to promotephagocytosis, while properdin can initiate the alternative pathway of complement activationto produce destruction of bacteria as well as foreign and abnormal cells. Because theseopsonic proteins are also produced in other organs, the loss of the splenic contribution to theirsynthesis is probably small. However, serum levels of both tuftsin and properdin are belownormal after splenectomy and in some diseases associated with hyposplenism.

The macrophages and histiocytes of the spleen remove bacteria and abnormal or foreign cellsand are especially effective in removing bacteria coated with antibody or opsonic proteins. Ifbacteria for which the host lacks pre-existing antibody are present in the bloodstream, thespleen's unique circulation makes it the major site for clearance of these bacteria as well as

the initial site for synthesis of IgM. When radioactively labeled bacteria are administered toanimals, the liver clears most of the well-opsonized microorganisms while the spleen removesthose that are poorly opsonized. When specific antibody is lacking to facilitate bacterialremoval by the liver, the spleen becomes the primary site for clearance. Encapsulatedbacteria, which resist antibody binding, are less effectively removed in an asplenic individualthan in a normal host. 8

The role of the spleen in removing malignant tumor cells is probably underestimated.Although large metastases to the spleen are uncommon, micrometastases occur frequently,with one study reporting 50% of spleens from patients with solid tumors containing neoplasticcells. Experimental evidence suggests that intense destruction of malignant cells in the spleenlimits the incidence of clinically apparent metastases.A third important immune function of the spleen is the production of specific antibody,

especially IgM. Particulate antigens, such as Salmonella flagella, lodge in the splenic red pulpand are transported by macrophages into the germinal centers where the IgM response isthought to occur. In asplenic individuals, IgM levels fall and the antibody response to a blood-borne antigen diminishes. Because of the anatomy of the splenic microcirculation, humoraland cellular antigens remain in contact with macrophages and lymphocytes for longer periods


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than in other areas of the reticuloendothelial system. The importance of an adequate timeperiod for interaction of these cells after antigen exposure is becoming apparent aslymphocyte and macrophage subpopulations responsible for humoral and cellular immunityare identified.

INDICATIONS FOR SPLENECTOMYTwo large series of studies illustrate the changing indications for splenectomy that haveaccompanied improved diagnosis and therapy of hematologic diseases. In one report of a 30-

year experience, splenectomy was performed for primary and secondary hypersplenism(41%), incidental to other operations (30%), for trauma (10.5%), for diagnosis (9%), forHodgkin's staging (8%), and for non-Hodgkin's lymphoma (NHL) (1.5%). The more recent 5-year experience, at the University of North Carolina, Chapel Hill, showed the indications forsplenectomy in 473 cases to be Hodgkin's staging (27%), incidental to other operations(20%), hypersplenism (16%), trauma (14%), NHL (7%), and diagnosis (7%).In a comparison between two series of splenectomies performed for hematologic disordersbetween 1946 and 1962 and 1963 and 1982, 400 splenectomies (20 per year) wereperformed between 1963 and 1982, compared with 94 (5.5 per year) during the earlierinterval. 50 A sharp decline occurred in the number of splenectomies performed each yearbetween 1974 and 1982. The evolution of the staging laparotomy for lymphomas, particularlyHodgkin's disease, with the decline in the average annual incidence of staging laparotomies

since 1974 was the major factor responsible. Contributing to the differences was an increasein the total number of splenectomies for hereditary spherocytosis, idiopathic hypersplenism,and myeloproliferative disorders. The average number of splenectomies for immunethrombocytopenic purpura increased significantly between the two time periods. Hairy cellleukemia (HCL) and Felty's syndrome emerged as indications for splenectomy during thesecond time period. Of the 400 splenectomies performed for hematologic disorders between1963 and 1982, the indications were therapeutic splenectomy (57%), Hodgkin's staging(40%), and diagnosis (3%).An improved understanding of immune anemia, thrombocytopenia, and neutrocytopenia hasclarified the role of splenectomy in many hematologic diseases. Some diseases, such asimmune thrombocytopenic purpura, appear to be increasing in incidence. Splenectomy as ameans of staging Hodgkin's disease is no longer such an important diagnostic test in theoverall approach to that disease, which now can be controlled in most patients using radiationtherapy and chemotherapy. Splenectomy for splenomegaly associated with selectedleukemias and NHLs is less commonly indicated because chemotherapy and radiation therapyhave become more effective. Hypersplenism, both primary and secondary, is now diagnosedless commonly because of better definition and classification of diseases that previously werelabeled as hypersplenic syndromes. The most frequent indications for splenectomy are nowtraumatic injury, immune thrombocytopenic purpura, and hypersplenism.In another report of splenectomy for hematologic disease, 81% of the patients underwentsplenectomy to control anemia, thrombocytopenia, neutropenia, or discomfort fromsplenomegaly. 36 In 19%, splenectomy was performed for diagnostic purposes, mostcommonly Hodgkin's disease staging. The morbidity rate of 25% accurately reflects the

frequency of complications that are related primarily to bleeding and infection. Sepsis is theusual cause of death after splenectomy for hematologic disease, and the mortality rateranges from 5% to 27%

Splenic Trauma The spleen is the most common intra-abdominal organ injured in blunt trauma and isfrequently injured in penetrating abdominal injury. Selected older reports reveal mortalityrates for splenic injury as high as 20%. Although some recent series report no deaths fromsplenic trauma, others still show a mortality rate approaching 10% because of the frequentassociation of other major organ injuries.Diagnosis. Injury to the spleen should be suspected in blunt upper abdominal injuries, whichcommonly occur in motor vehicle or bicycle accidents. Splenic injuries are often associated

with fractured ribs of the left chest. The diagnosis and clinical course of an isolated splenicinjury is variable. The spleen receives approximately 5% of the cardiac output, and a largelaceration through the body of the spleen can extend into the splenic pedicle, causingextensive and continued hemorrhage, abdominal distention with hemoperitoneum, and shock.More commonly, a laceration deep into the pulp occurs or an adhesion between the spleen


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and its ligaments or diaphragm causes capsular avulsion with cessation of hemorrhage afteran initial blood loss of 500 to 750 ml. If the injury does not involve the major splenicvasculature and is limited to the pulp or capsule, the patient may remain hemodynamicallystable. However, subcapsular hematomas can form, which have the potential to rupture at atime remote from the injury, accounting for the phenomenon of delayed rupture of the spleen.Alternatively, some subcapsular hematomas evolve into splenic cysts while others resolvewith fibrosis and scarring . Unfortunately, in the acute setting of evaluating the stable patientwith splenic injury, it is difficult to identify which splenic injuries will resolve without operative

management.If a splenic injury is suspected, admission to the hospital for monitoring is mandatory.Although many useful measures are available to aid in the diagnosis of splenic injury, theirapplication requires a high index of clinical suspicion. A careful history should be obtained toinclude delineation of pain and a mechanism of injury consistent with splenic trauma. Usuallyinjury to the left upper abdomen associated with fractured ribs of the left anterior chest alertsthe clinician to proceed with evaluation by specific diagnostic tests. If the patient is in shockwith hemoperitoneum, the diagnosis of splenic injury is established at laparotomy.

The signs and symptoms of splenic trauma are those of hemoperitoneum. Generalized andnonspecific abdominal pain in the left upper quadrant occurs in approximately one third ofpatients with splenic injury. Pain referred to the tip of the left shoulder (Kehr's sign) isinconstant, varying in incidence from 15% to 75%, and is unreliable for excluding splenic

injury but is useful for enhancing the diagnostic probability if present. Kehr's sign is elicited bybimanual compression of the left upper quadrant after the patient has been in

Trendelenburg's position for several minutes preceding the maneuver. On rare occasions,patients with splenic injury have a palpable tender mass in the left upper quadrant (Ballance'ssign), caused by an extracapsular or subcapsular hematoma with omentum adherent to theinjured spleen.Patients with splenic trauma usually have hemoglobin/hematocrit values that are 10% to 30%below normal and a moderate leukocytosis. Diagnostic peritoneal lavage is a useful andinexpensive maneuver, which may reveal gross blood or an elevated red blood cell countdiagnostic of intraperitoneal hemorrhage. When intraperitoneal hemorrhage is diagnosed byperitoneal lavage, laparotomy is performed to diagnose and treat all bleeding viscera,including the spleen.A variety of imaging techniques are useful in the diagnosis of splenic injury. Standardabdominal or contrast radiography may reveal depression of the splenic flexure of the colonand medial displacement of the stomach in patients with an injured spleen but are lessreliable in establishing the diagnosis of splenic trauma than isotope or scanning techniques.Splenic angiography can demonstrate a variety of splenic injuries but is used infrequentlybecause of the equal or greater accuracy of diagnostic peritoneal lavage and less invasiveimaging techniques. Ultrasonography of the spleen can provide evidence of free blood andhematoma surrounding the splenic capsule with reasonable accuracy. Isotope scans ( 99mTcsulfur colloid) are popular in many centers for the acute diagnosis of splenic injury with adiagnostic accuracy rate exceeding 90%. However, computed tomography (CT) is probablythe most accurate method available for diagnosing splenic injury .

Reports of imaging techniques reveal a high sensitivity and specificity (>90%) for thediagnosis of splenic injury; however, considerable variation exists in the skill and enthusiasmof different radiologic units performing the tests for suspected splenic injury. Although CT andisotope imaging techniques are accurate methods for establishing the diagnosis of an injuredspleen, the accuracy in individual instances is in large part dependent on the skill of theradiologist.Changing Concepts in the Treatment of Ruptured Spleen. In recent years the spleen'simportant role in cellular and humoral immunity has been clarified and the danger ofoverwhelming bacterial infection in asplenic patients has been established. Consequently,operative techniques for splenic preservation have been developed, and a concept fornonoperative management of selected splenic injuries is evolving. Although periodic reportsof repairing injured spleens by use of suture or cauterization have been available for many

years, interest in partial splenectomy has been rekindled since 1960. In animal and humanstudies, it has been shown that segmental resection of the spleen is practical and safe. Inaddition to partial splenectomy, splenorrhaphy, ligation of segmental vessels, and capsularrepair are useful techniques for splenic salvage. Splenic salvage operations have been greatlyaided by the development and use of topical hemostatic agents such as microfibrillar collagen


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(Avitene) and a variety of absorbable envelopes to aid in hemostasis from splenic injuries. 28Although technically more difficult than splenectomy, splenic repair can be performed withcomparable transfusion requirements, reoperation rates, and morbidity.Conservatism in the management of splenic injury has extended beyond repairing andpreserving an injured spleen when possible. Because bleeding from splenic trauma appears tobe more self-limited in children than in adults, nonoperative therapy may prove to be safe inselected pediatric patients. Nonoperative therapy requires a stable patient who is found bydiagnostic tests to have an isolated splenic injury. At The Hospital for Sick Children (Toronto),

where nonoperative management of splenic injury has been pioneered, 75 children withsplenic injury were treated between 1981 and 1986. Ten (13%) required splenectomy orsplenorrhaphy, but the remaining 65 patients (87%) were successfully managednonoperatively. Of those patients treated nonoperatively, only 23% required bloodtransfusions. In comparison to an earlier report, current guidelines for management haveresulted in an increased number of patients managed nonoperatively, a reduction in thenumber of patients receiving blood transfusions, and a decrease in the length of both hospitalstay and time spent in the intensive care unit.In one large series of injuries associated with splenic trauma an appropriate note of cautionwas suggested before nonoperative management of splenic trauma is adopted. 47 In 258patients with splenic injury, concomitant injuries requiring operative therapy were present in36.5% of those with blunt trauma and 94% of patients with penetrating injury. Children

younger than the age of 16 had an incidence of intra-abdominal injuries in addition to thespleen of 32.6% for blunt trauma and 100% for penetrating trauma.One pitfall of nonoperative management of splenic trauma lies in the significant possibility offailing to diagnose and treat concomitant intra-abdominal injuries. An additional concern isthat most reported series of nonoperative management of splenic injuries include patientswith blood transfusion requirements substantial enough to expect an incidence of transfusion-related hepatitis greater than the statistical probability of postsplenectomy sepsis. In addition,hospital time is usually longer for nonoperative management (1316 days) compared withoperative management (7 days) with a longer period for convalescence.

The recommended management in adults with hemoperitoneum and demonstrated splenicinjury is laparotomy with the expectation that 30% to 50% of spleens may be salvaged withsufficient (>50%) splenic pulp retained to preserve immune function. In both children andadults with splenic injury secondary to penetrating wounds, laparotomy should be performedbecause of the risk of significant injury to other intra-abdominal organs. All patients in shockor with significant transfusion requirement should have exploratory laparotomy for control ofhemorrhage from the spleen and management of any other injured structures.Nonoperative treatment of splenic trauma in children is prudent only for the stable patientwho is being followed in an appropriate hospital area by surgeons experienced innonoperative management. There should be no hesitation to proceed with laparotomy andsplenic repair. Operation is well tolerated, and splenic salvage techniques are probably morefeasible in children than adults because of the higher ratio of splenic capsule to pulp. Anymortality from nonoperative management of splenic injury in children is unacceptable.Delayed Rupture of the Spleen. As early as 1866, Evans suggested that the spleen might

bleed catastrophically at a time remote from injury. 43 It was postulated that injury to thepulp of the spleen could not be contained indefinitely by the thin splenic capsule undercontinuous arterial pressure. The usual interval between injury and the onset of clinicallyapparent intra-abdominal hemorrhage (period de latence, Baudet, 1907) is within 2 weeks,although longer intervals have been reported. 43 Although the incidence of delayed rupture ofthe spleen has been reported to be 15% to 30%, the criteria for diagnosis are variable andunconvincing. 43 It is apparent from splenic injuries managed nonoperatively that many healby fibrosis and without sequelae. The entity of delayed rupture of the spleen is more properlyreferred to as delayed diagnosis of splenic injury. As imaging techniques for follow-up ofsuspected or proved splenic trauma become commonplace, it is likely that delayed rupture ofthe spleen will cease to be an entity with clinical meaning or application.Splenosis and Splenic Implants. Splenosis is the autotransplantation of splenic tissue after

splenic trauma. Although fewer than 200 cases have been reported, the true incidence ofsplenosis undoubtedly is more common because of the high incidence of traumatic injury tothe spleen. Appearing as sessile or pedunculated dark red nodules, splenic implants vary froma few millimeters to several centimeters in diameter. Splenic implants depend on a bloodsupply from small arteries penetrating the capsule and usually remain small or outgrow their


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blood supply and undergo infarction. Splenosis may occur anywhere in the peritoneal cavityand has been reported on the pericardium and the pleura as well as in the subcutaneoustissue of abdominal incisions. 10 Splenosis seldom causes symptoms and is usuallydiscovered as an incidental finding at reoperation years after splenic trauma. Isolated reportshave described splenosis producing intestinal obstruction from adhesions, stomach massessimulating carcinoma, and pain, presumably from torsion.Recent interest in the postsplenectomy sepsis syndrome has heightened interest in splenosisas potentially valuable for preservation of immune function by providing splenic implants at

the time of removal of an injured spleen. Splenosis can be produced in a variety of animals bytransplantation of splenic pulp. Von Stubenrauch seeded crushed splenic pulp throughout theperitoneal cavity in dogs and believed that splenoids arose de novo from the peritoneum.Perla described the histologic sequence of splenic transplants in rats. After transplantation,splenic implants underwent degeneration with only the reticulum cells at the peripheryremaining viable after 24 hours. Regeneration of splenic tissue appeared to originate from thereticulum cell precursor. 10 Recently, investigators interested in preserving the immunefunction of the spleen have injected splenic pulp into the liver to avoid mechanical problemsfrom adhesions that sometimes develop in association with splenosis.Splenosis, the born-again spleen, may provide the blood management functions of the spleen.

The absence of Howell-Jolly bodies, siderocytes, and other postsplenectomy blood changes aswell as the recurrence of the hematologic disease for which splenectomy was performed

should raise suspicion of splenosis or the presence of accessory splenic tissue. Splenosis hasbeen reported in conjunction with the expected postsplenectomy blood changes, suggesting acritical mass of splenic tissue is needed for recovery of splenic function. Residual splenictissue can be detected by isotope scanning using 99mTc sulfur colloid .Splenic reticuloendothelial function has been investigated in a series of patients previouslyundergoing total splenectomy, partial splenectomy and splenic repair, and splenicautotransplantation. 48 Partial splenectomy and splenorrhaphy resulted in normal splenicreticuloendothelial function that was indistinguishable from a control group of patientssustaining trauma but who had intact spleens. Extraperitoneal splenic autotransplantationresulted in the preservation of a small amount of reticuloendothelial function. The subnormalreticuloendothelial function achieved by splenic autotransplantation was clearly superior tothat resulting from total splenectomy without deliberate splenic autotransplantation. Splenicautotransplantation, which in this study involved placing thin slices of spleen weighing a totalof 25 to 30 gm. into an anterolateral extraperitoneal pocket, appeared to be safe and was notassociated with increased postoperative complications.Although autotransplanted splenic tissue, accessory splenic tissue, and splenosis can restoresome of the spleen's blood management functions and antibody synthesis, it is unclear howmuch splenic tissue is needed for protection against overwhelming postsplenectomy sepsis.Studies have failed to identify re-establishment of resistance to postsplenectomy sepsis afterautotransplantation of splenic tissue. Death from postsplenectomy sepsis has occurred inchildren and adults having a total mass of residual splenic tissue weighing 3 to 92 gm.Although residual splenic tissue can restore some of the spleen's functions, a critical amountof splenic tissue is required for full protection against postsplenectomy sepsis.

Immune Thrombocytopenic PurpuraImmune thrombocytopenic purpura (ITP, previously called idiopathic thrombocytopenicpurpura) is a syndrome characterized by a persistently low platelet count. Thethrombocytopenia is caused by a circulating antiplatelet factor that causes plateletdestruction by the reticuloendothelial system. In most patients, the antiplatelet factor is animmunoglobulin (IgG) antibody directed toward a platelet-associated antigen. Circulatingimmune complexes may have a causal role in some cases, but their precise role is unclear.Proof of autoimmunity is lacking. 31

The majority of patients with ITP are young women. In Schwartz's series, the average age was36 years and the duration of clinical symptoms before splenectomy was 24 weeks, with anaverage preoperative platelet count of 33,000 per cu. mm. 41 ITP is increasing in frequency,and the disease is being diagnosed more often now in men. This increase results in part from

the association of immune thrombocytopenia with the acquired immunodeficiency syndrome(AIDS) and an increasing occurrence of ITP in three groups of patients at risk for developingAIDShomosexual men positive for human immunodeficiency virus (HIV), parenteral drugabusers, and hemophiliacs receiving multiple transfusions. The diagnosis of ITP is suggestedby spontaneous and easy bruising, petechiae, and mucosal bleeding. Menorrhagia is common,


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and prolonged bleeding after shaving trauma may be an initial complaint in males.Intracranial hemorrhage is a rare and usually fatal complication.

The propensity for hemorrhage is reflected by the level of thrombocytopenia. A bleedingdiathesis is unlikely with thrombocytopenia in the range of 50,000 to 100,000 per cu. mm.Bleeding with minor trauma or surgical procedure can be expected with platelet counts in therange of 20,000 to 100,000 per cu. mm. Spontaneous bleeding with purpura and petechiae,epistaxis, menorrhagia, gingival bleeding, and so on, occurs commonly with platelet countsbelow 20,000 per cu. mm. and especially below 5,000 per cu. mm.

Crosby has suggested classifying patients with thrombocytopenia into those with dry purpura(petechiae and ecchymoses) and those with wet purpura (active bleeding from mucosalsurfaces). This distinction postulates that patients with wet purpura are at increased risk forcentral nervous system bleeding and thus require aggressive treatment.Patients with easy bruisability or hemorrhage require a careful history with special emphasison recent exposure to quinine, quinidine, sulfonamides, and thiazides that may produce drug-dependent antibodies and immune thrombocytopenia. Isoantibodies against transfusionproducts can also cause thrombocytopenia. Collagen disease such as systemic lupuserythematosus may be indistinguishable in initial presentation from ITP. 26, 31Pseudothrombocytopenia, a phenomenon in which the platelet count is spuriously low, resultswhen antibodies in the patient's serum react with platelets in blood anticoagulated withethylenediaminetetraacetic acid (EDTA), causing agglutination. Platelet clumping results in a

falsely low platelet count that will be at variance with the estimated number of plateletspresent on a peripheral blood smear obtained by fingertip puncture. EDTA-dependent plateletantibodies have been detected in several patients erroneously diagnosed as having ITP.Diagnosis of immune thrombocytopenia requires the exclusion of drug-dependent antibodies,isoantibodies, collagen vascular disease, lymphoproliferative disorders, thyroid disease,recent viral illness, and spurious thrombocytopenia. Patients with classic ITP rarely have apalpable spleen (


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sensitization has occurred, phagocytosis is triggered by the Fc portion of the IgG molecule orby complement activation with C3b fixation to the platelet surface. The macrophage Fcreceptor mechanism clearly is important as increased platelet-bound IgG is present inessentially all patients with ITP. Macrophage Fc and C3b receptors may act synergistically,resulting in a greatly enhanced phagocytic efficiency.Because 30% of the total circulating platelet mass is within the spleen at all times as anexchangeable platelet pool, the spleen is the most active site of platelet destruction. Thestagnant blood flow in the splenic microcirculation allows sensitized platelets to be readily

removed by phagocytic cells lining the reticular network of the red pulp. Having no residentplatelet pool and possessing a rapid microcirculation by contrast, the liver assumes a majorrole in platelet destruction when severe disease and high antibody titers result in heavilysensitized platelets. The bone marrow is the most likely source of antibody in patients whohave undergone splenectomy. 31 Intramedullary platelet destruction and inhibition ofthrombopoiesis may occur as a result of antiplatelet antibody binding to both platelets andmegakaryocytes, although the efficiency of the marrow reticuloendothelial system is belowthat of the liver and the spleen.A study investigating the mechanisms of increase in the platelet count after treatment of ITPdetermined the survival time and localization of radiolabeled autologous platelets andmeasured platelet-associated immunoglobulin levels before and after prednisone therapy orsplenectomy. 12 Prednisone therapy produced an increased platelet count from increased

platelet production. The increased platelet count after splenectomy correlated with increasedplatelet survival. The degree of radiolabeled platelet localization in the liver was normal inpatients in whom splenectomy was effective and was increased to above normal in patients inwhom splenectomy was ineffective. The conclusion that prednisone improves platelet countsprimarily by increasing platelet production requires modification of the pathophysiologicconcept of ITP to incorporate the hypothesis that in some patients the predominant cause ofthrombocytopenia is ineffective marrow production of platelets rather than acceleratedplatelet removal.In summary, thrombocytopenia in patients with ITP usually occurs from a combination ofintramedullary platelet removal by reticuloendothelial cells, causing ineffective plateletproduction and decreased survival of circulating platelets due to peripheral sequestration anddestruction in the spleen and liver. Successful therapy may produce an increase in theplatelet count either by increasing the effective production of platelets or by decreasingperipheral platelet sequestration and destruction. Splenectomy appears to increase plateletsurvival by removing a major organ of peripheral destruction. If the liver is the major site ofplatelet destruction, splenectomy may not result in improvement in the platelet count.

Treatment. The goal of therapy in chronic ITP is to obtain a complete and sustained remissionof the disease and to remove the patient from the risks of hemorrhage. This can be achievedin 80% to 90% of patients.When ITP is initially diagnosed, the patient should be hospitalized. A patient having activebleeding should remain at bed rest and have specific therapy instituted. Platelet transfusionsprovide immediate benefit and should be administered as needed to control bleeding.Although transfused platelets rapidly become coated with antibody and destroyed and

provide only transient benefit, they afford protection against life-threatening bleeding. High-dose intravenous gamma-globulin is also useful but requires several days for a beneficialplatelet increase to occur.Corticosteroid therapy (prednisone, 1 mg. per kg. per day or the therapeutic equivalent) isinstituted at the time of diagnosis. Most patients with ITP are improved with administration ofcorticosteroids, with an increase in the platelet count occurring within 3 to 7 days andreaching a maximum in several weeks. 31 Complete and sustained remission withcorticosteroid therapy is rare, although rates as high as 25% have been reported. 31 In mostcases, even if the platelet count becomes normal, the response is transient, andthrombocytopenia recurs as the corticosteroid dose is tapered.Splenectomy should be performed in patients with ITP that is refractory to corticosteroidtherapy. In the majority of patients, splenectomy is performed electively. Emergent

splenectomy is necessary in patients with ITP who have evidence of central nervous systembleeding.Complete remission after splenectomy is more likely in patients who have shown a responseto corticosteroids. Additional clinical features indicating the likelihood of a favorable responseto splenectomy include patients who are younger than 60 years old, who have disease of


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relatively short duration, and who exhibit a prompt thrombocytosis with platelet countsreaching 500,000 per cu. mm. or more after splenectomy. Most patients, however, areimproved after splenectomy, even if their platelet counts were not significantly increased bycorticosteroid therapy.Eighty-eight percent of Schwartz's patients responded to splenectomy and developed normalplatelet counts. Of those responding to splenectomy, 20% had platelet counts exceeding100,000 per cu. mm. by the third postoperative day, and 90% of them had normal plateletcounts after 1 week. The remaining responders developed normal platelet counts within 1 to 6

months postoperatively. In three patients, thrombocytopenia recurred after a long intervaland was attributed in one patient to an accessory spleen.The level of platelet-associated IgG falls to normal after a response to splenectomy due to theremoval of a large site of antiplatelet antibody production. 31 A corticosteroid response is alsoaccompanied by a decrease in platelet-associated IgG. An increase in the platelet count oftenoccurs before platelet-associated IgG falls because of the corticosteroid influence on thereticuloendothelial system. A response to immunosuppressants such as cyclophosphamideand vincristine is also associated with a decrease in platelet-associated IgG.ITP During Childhood. In children, particularly those younger than age 6, ITP often appearsafter a viral upper respiratory tract infection. In contrast to the adult form of the disease,childhood ITP usually undergoes spontaneous remission without specific therapy. A shortcourse of prednisone therapy is usually prescribed; however, a clear benefit has not been

demonstrated. 26Intracranial hemorrhage is a life-threatening complication of childhood ITP and occurs in 1%to 2% of cases. It is responsible for the majority of deaths from the disease in this age group.

The risk of intracranial hemorrhage is greatest during the first month of the illness. Mostreported cases appear to be spontaneous, but minor head trauma may result in intracranialhemorrhage in patients with platelet counts below 10,000 to 20,000 per cu. mm. 52Development of intracranial hemorrhage in ITP is an indication for emergency splenectomy.Spontaneous and complete remission occurs in approximately 85% of children with ITP. Thosein whom spontaneous remission does not occur within 1 year are considered to have chronicITP and usually undergo elective splenectomy to avoid the risks of chronic thrombocytopenia.Splenectomy and Perioperative Therapy for ITP. Most patients are referred for splenectomyafter corticosteroid therapy has failed to achieve a complete and sustained remission. A smallgroup of patients have ITP diagnosed due to abnormal bleeding during surgical procedures orafter injury. A third group of patients require emergent splenectomy for intracranialhemorrhage.High-dose intravenous gamma-globulin is very effective in achieving an increase in theplatelet count preoperatively in patients who do not respond to corticosteroids or are notcandidates for corticosteroid therapy. It is postulated that intravenous gamma-globulintherapy promotes a rise in the platelet count due to temporarily reducing platelet destructionby saturating macrophage Fc receptors, thus producing a transient blockade of thereticuloendothelial system. A significantly improved platelet count (100,000250,000/cu.mm.) occurs within 4 to 6 days and provides a therapeutic window for performance ofsplenectomy. 23, 51 In addition to affecting an increase in the platelet counts of patients

failing to respond to corticosteroids or who are not candidates for corticosteroid therapy, high-dose gamma-globulin therapy is appropriate for the patient with ITP needing urgentsplenectomy in whom a trial of corticosteroids is not warranted and in the pregnant patientwith ITP late in the third trimester of pregnancy.Immunizations with polyvalent pneumococcal vaccine , Haemophilus influenzae vaccine, andNeisseria meningitidis vaccine should be administered as soon as it becomes likely thatsplenectomy will be performed. Ideally these immunizations should be carried out 10 to 14days preoperatively. It is probable that patients receiving corticosteroids have a suboptimalearly response to these vaccines but ultimately will develop protective antibody titers. Theavailability of blood and platelets for transfusion should be ensured, although the need forblood transfusion is rare. Intraoperative thrombocytopenic bleeding usually ceases after thesplenic artery is ligated. In Schwartz's series, platelets were not used preoperatively and were

administered intraoperatively or postoperatively in only 9 of 120 patients having splenectomyfor ITP. Although a nasogastric tube is advisable for postoperative gastric decompression inmost patients undergoing splenectomy, some avoid use of a nasogastric tube in patients withITP because of the potential risk of precipitating hemorrhage from the nose or nasopharynx.


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Splenectomy can be performed through a variety of abdominal incisions. The midline incisionis preferred in ITP because it allows entry into the peritoneal cavity without transection ofabdominal muscles and thus reduces the potential for postoperative muscle hematoma. Thespleen, usually of normal size, is assessed for adhesions and the nature of its ligamentousattachments. Splenic ligaments vary considerably in composition, being thin membranesaffording easy dissection in some patients and being thick and tendinous in others. Thetechnique for splenectomy is a matter of personal preference. The authors prefer thesequence of initially incising the posterior splenic ligaments followed by mobilizing the spleen

and tail of the pancreas toward the midline for subsequent dissection of the splenic vessels inthe hilus. Caution is taken to avoid excessive traction or trauma to the tail of the pancreas.Division of the gastrosplenic ligament is performed with suture ligation of the gastric ends ofthe short gastric arteries. After removal of the spleen, laparotomy pads are placed in the leftupper quadrant while a search is made for accessory splenic tissue. Approximately 20% ofpatients have an accessory spleen, and common sites are the splenic hilus, adjacent to thesplenic vessels and tail of the pancreas, greater omentum, and gastrosplenic and gastrocolicligaments. Rarely has an accessory spleen been found in the intestinal mesentery, presacral,and gonadal regions. The left upper quadrant is not drained routinely. Indications for closedsuction drainage are injury to the pancreas during hilar dissection and incomplete hemostasis.During the immediate postoperative period, corticosteroid therapy is continued intravenously,and the platelet count is monitored. It usually is possible to begin tapering the corticosteroid

dose immediately, and in patients demonstrating a satisfactory thrombocytosis,corticosteroids are gradually reduced over 4 to 6 weeks and discontinued.

The mortality rate for splenectomy in ITP is under 2% and occurs primarily in patients withintracranial hemorrhage. In approximately 80% of adult patients who have splenectomy forITP, the platelet count returns to normal or above-normal levels within the first 6 weeks afteroperation. 31 In approximately 15% there is substantial improvement in the platelet countfrom preoperative levels, but it does not reach a normal level. Only about 5% of patientsremain severely thrombocytopenic after splenectomy and require some form of chronictherapy. In these patients with refractory ITP, therapy having the least side effects is chosento maintain the platelet count at a safe level (30,000 to 50,000/cu. mm.). Ingestion ofantiplatelet drugs, trauma, azotemia, fever, and infection increases the bleeding tendency inthrombocytopenic patients. 31 Immunosuppressants such as cyclophosphamide, Vincaalkaloids (vincristine and vinblastine), azathioprine, and danazol, a modified androgen, havebeen used to treat patients with refractory ITP, with variable results.

Thrombotic Thrombocytopenic Purpura Thrombotic thrombocytopenic purpura (TTP, Moschcowitz's syndrome) is a syndromecharacterized by thrombocytopenia, microangiopathic hemolytic anemia, fluctuatingneurologic abnormalities, progressive renal failure, and fever. TTP is produced by widespreaddeposition of platelet microthrombi, and the pentad of clinical manifestations results fromocclusion of arterioles and capillaries by subendothelial and intraluminal deposits of hyaline

material composed of aggregated platelets and fibrin. The etiology of TTP is unknown, andapproximately 90% of the cases of TTP are idiopathic. The pathologic response in TTP may beinitiated by various stimuli, including viral and bacterial infection, pregnancy, drugs (oralcontraceptives, mitomycin, and cyclosporine), and nonspecified toxins. The syndrome hasbeen associated with systemic lupus erythematosus and other connective tissue disorders,malignancies, and more recently with AIDS. TTP has a peak incidence in the third decade oflife and occurs more frequently in females than in males.

The differential diagnosis includes hemolytic-uremic syndrome, disseminated intravascularcoagulation, drug reaction, eclampsia, aplastic anemia, idiopathic AIHA, ITP, leukemia,paroxysmal nocturnal hemoglobinuria, periarteritis nodosa, infection, systemic lupuserythematosus, and exposure to toxins. The exact role of the spleen in TTP is unclear, butapproximately 20% of patients will have splenomegaly.

Prognosis for untreated patients with TTP is very poor, with less than 10% surviving beyond 1year. 23 The current therapeutic regimen of infusions of fresh-frozen plasma results indramatic improvement for the majority of patients with TTP. A combined therapeuticapproach using plasma therapy, antiplatelet agents (aspirin and dipyridamole) and high-dose


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corticosteroid therapy is instituted immediately after the diagnosis is established. Plasmainfusion or plasma exchange using plasmapheresis and replacement with fresh-frozen plasmaachieves response rates between 70% and 90%. 23 It is speculated that plasma infusion orplasma exchange replaces a deficient plasma component or removes some toxic substance.23, 51 Immunosuppressive drugs (vincristine and azathioprine) are also beneficial adjunctiveagents in the present combined therapeutic approach for TTP. If combined-modality therapyfails, splenectomy should be performed. Splenectomy occasionally results in spectacularimprovement, particularly when combined with high-dose corticosteroid therapy and

antiplatelet drugs. 23 Although a clear physiologic explanation is lacking for this occasionalresponse to splenectomy, prior experience has documented that 70% of the long-termsurvivors with TTP were patients who had undergone splenectomy.HypersplenismHypersplenism is a concept, probably first used by Chauffard in 1907, which refers to avariety of ill effects resulting from increased splenic function that may be improved bysplenectomy. 23, 51 Criteria for diagnosis include: (1) anemia, leukopenia,thrombocytopenia, or combinations thereof; (2) compensatory bone marrow hyperplasia; (3)splenomegaly; and (4) improvement after splenectomy. 8, 23, 51 Hypersplenism is classifiedas primary when an underlying disease cannot be identified to account for the exaggeratedsplenic function. Secondary hypersplenism refers to those cases in which a specific or more-or-less well-defined disorder has been diagnosed. Because it now is possible to obtain more

specific diagnoses for many patients who previously would have been thought to haveprimary hypersplenism, primary hypersplenism is now diagnosed much less frequently thansecondary hypersplenism.Primary hypersplenism was initially described in 1939 by Doan and Wiseman as an illnessconsisting of neutropenia and splenomegaly for which splenectomy was curative. 40 Thedefinition of the syndrome subsequently was broadened to include patients with variabledegrees of anemia, thrombocytopenia, or pancytopenia. Subclassification of primaryhypersplenism is used to describe splenic hyperfunction producing depression of one or moreof the formed elements of the blood (red cells, white cells, and platelets). Primary splenicpanhematopenia (pancytopenia) refers to depression of all formed elements, whereas inprimary splenic neutropenia, depression of the white blood cells is the prominent feature.Most patients with primary hypersplenism are women. Clinical manifestations are dependenton the specific formed elements that are depressed and include pallor and other signs ofanemia, fever, recurrent infections, oral ulcerations, ecchymoses, and petechiae.Splenomegaly is common. The peripheral blood smear shows leukopenia or varying degreesof pancytopenia without evidence of leukemia or myeloproliferative disorders. Pancellularhyperplasia is present in the bone marrow.Primary hypersplenism is a diagnosis of exclusion and should be accepted only after anexhaustive search for a specific etiology of hypersplenism has been unrewarding.Corticosteroids are seldom of benefit in primary hypersplenism. Splenectomy is indicatedwhen the diagnosis is established and usually results in marked hematologic improvement forvirtually all patients. Occasional patients have subsequently developed reticulum cell sarcomaor histiocytic lymphoma.

Lymphoma having primary presentation in the spleen may present as asymptomaticsplenomegaly with or without hypersplenism. Radionuclide studies, CT, and magneticresonance imaging usually reveal nonspecific, featureless organ enlargement. If parenchymalexpansion secondary to tumor infiltration and congestion becomes massive, splenic poolingand increased regional blood flow may result in hypersplenism. Lymphoma with primarypresentation in the spleen may result in the diagnosis of idiopathic splenomegaly untilsplenectomy permits accurate histopathologic diagnosis.Secondary hypersplenism classically refers to a syndrome of pancytopenia (anemia,thrombocytopenia, and leukopenia) associated with portal hypertension from intrahepatic orextrahepatic portal or splenic vein obstruction. Hypersplenism associated with portalhypertension secondary to cirrhosis seldom requires splenectomy. Cytopenias commonly areimproved after a shunt between the portal and systemic circulations, presumably caused by

relief of congestive splenomegaly. Splenic vein thrombosis with bleeding from gastric varicesshould be treated by splenectomy, which usually cures the gastric variceal bleeding and anyexisting hypersplenism.


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Secondary hypersplenism includes a number of diseases sharing the common feature ofsplenomegaly. Rather than listing these, it is more appropriate to consider the mechanismsproducing splenic enlargement

8 Work hypertrophy from immune response and/or red blood cell destruction, venouscongestion, myeloproliferation, infiltration, and neoplastic proliferation within the spleenproduce variable degrees of splenomegaly. Diverse pathophysiologic mechanisms areinvolved in the resulting hypersplenism . 8 In both primary and secondary hypersplenism, thedegree of splenomegaly does not correlate closely with the severity of clinical symptoms or

the degree of depression of formed elements of the blood.HyposplenismHyposplenism is a potentially lethal syndrome characterized by diminished splenic function.Hyposplenism was first described by Dameshek in 1955 in a patient with sprue who had anasplenic peripheral blood picture with Howell-Jolly bodies and target cells. 8 As in the asplenicpatient, other peripheral blood findings that suggest hyposplenism are the presence ofacanthocytes and siderocytes, a long-term lymphocytosis and monocytosis, and a mildthrombocytosis. 8 Diagnosis of hyposplenism is confirmed by an isotope scan ( 99mTc sulfurcolloid) revealing an atrophic spleen. Hyposplenism can occur in the presence of a normalsized or an enlarged spleen .

The danger of hyposplenism is the risk of developing potentially lethal sepsis (see TheProblem of Overwhelming Postsplenectomy Sepsis). Sickle cell anemia is the most common

disease associated with hyposplenism. Children with sickle cell anemia are vulnerable tooverwhelming pneumococcal infection similar to that seen in asplenic children. The child withsickle cell anemia is most vulnerable when the spleen is enlarged. By the time the spleenbecomes atrophic from recurrent infarctions (autosplenectomy), the patient will havedeveloped some immunity from exposure to different pneumococcal strains.

The most common surgical disease associated with hyposplenism is chronic ulcerative colitis,in which 40% or more of patients develop hyposplenism as the pancolitis progresses. Otherconditions associated with hyposplenism in which the surgeon is commonly involved includethyrotoxicosis, corticosteroid administration, and patients who have received Thorotrast(thorium dioxide) as a radiocontrast agent. If a patient is suspected or proved to havehyposplenism, the same precautions against sepsis recommended for asplenic patientsshould be instituted.Hodgkin's DiseaseDescribed by Thomas Hodgkin in 1832, Hodgkin's disease is a malignant lymphomacharacterized by the presence of typical, multinucleate giant cells. The unique cell, describedby Sternberg and later Reed around the turn of the century, is essential for diagnosis.Hodgkin's disease is relatively rare, with a bimodal age-incidence curve that peaks in the late20s and declines to the mid 40s. After age 45, the incidence of Hodgkin's disease increaseswith age. The disease is slightly more common in men than women.Most patients with Hodgkin's disease have asymptomatic lymphadenopathy at the time ofdiagnosis. The site of initial nodal involvement is the cervical area in most patients (65%80%), followed by the axillary (10%15%) and inguinal (6%12%) regions. Retroperitoneallymph nodes may be involved but require lymphangiography or CT for diagnosis. Mediastinal

involvement occurs in 6% to 11% of patients at the time of diagnosis.Constitutional symptoms (B symptoms) such as fever, night sweats, weight loss, and pruritusare usually indicative of widespread involvement and are unfavorable prognostic signs. Theymay appear simultaneously with lymph node enlargement or may precede development oflymphadenopathy. A typical fever pattern is a high temperature alternating for a few dayswith an afebrile period (Pel-Ebstein fever). Less specific constitutional symptoms includelocalized acute discomfort in areas of adenopathy after ingestion of alcoholic beverages,malaise, lethargy, easy fatigability, generalized weakness, and anorexia.Many patients have a mild normochromic normocytic anemia. One third have a leukocytosisdue to a neutrophil increase, and eosinophilia is present frequently. Lymphopenia is commonin the later stages of the disease. The platelet count is normal initially but is frequentlydepressed in advanced disease. There is a progressive loss of T-lymphocyte function with

reduced cell-mediated immunity.A classification of Hodgkin's disease was developed by the international symposium held inRye, New York, in 1965, at which time the earlier classifications were simplified. In the Ryeclassification there are four histopathologic subtypes of Hodgkin's disease: lymphocytepredominance, nodular sclerosis, mixed cellularity, and lymphocyte depletion. Lymphocyte


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predominance and nodular sclerosis subtypes have a more favorable prognosis than mixedcellularity and lymphocyte depletion subtypes. However, the prognostic implications ofsubtyping are becoming less useful because of the excellent results of current aggressivetreatment.Hodgkin's disease metastasizes initially in a predictable, nonrandom pattern throughlymphatic channels to contiguous lymph node groups and organs with a prominent lymphatictissue component. The predictable mode of spread of Hodgkin's disease provides the basis forirradiation of adjacent lymph node areas in patients with apparently localized disease. 3

Treatment and ultimately survival of the patients with Hodgkin's disease depend on theanatomic distribution of the disease and the presence or absence of specific symptoms, thestage of the disease, and the histopathologic subtype.Histopathologic diagnosis is made by lymph node biopsy in which the largest and mostcentrally placed node should be selected for excision. In a matted group or cluster of nodes, acentral node from the group should be excised or a generous incisional biopsy specimenobtained. Nodes from the lower cervical or axillary areas provide the most satisfactory tissuefor histopathologic evaluation, because nodes from the parotid, submandibular, and inguinalregions often show changes due to previous inflammatory processes in their regions ofdrainage. When only mediastinal adenopathy is present, biopsy is performed throughmediastinoscopy or thoracotomy, as indicated. Laparotomy is seldom required to obtain theinitial diagnosis in Hodgkin's disease.

Since the concept of staging was introduced approximately 30 years ago, the staging processhas undergone continued modification with the intent of accurately defining the anatomicsites of involvement and thus improving patient selection for the most appropriate type andamount of therapy. Stage I disease indicates nodal involvement in only one lymph noderegion. Stage II disease is limited to two or more lymph node regions on the same side of thediaphragm. Stage III refers to disease involving lymph node regions on both sides of thediaphragm (the spleen is considered a lymph node). Stage IV disease encompasses diffuse ordisseminated involvement of one or more distant extranodal organs with or withoutassociated lymph node involvement. Stage IV is further classified as A (absence) or B(presence) with regard to fever, night sweats, weight loss, and pruritus. The subscript E isused to classify selected patients having localized extranodal disease in Stages I to III (e.g.,lung, muscle, bone, skin) contiguous to involved nodes. In general, the E designation isreserved for patients having extralymphatic disease so limited in extent and/or location that itis amenable to definitive treatment by radiotherapy. The S subscript indicates splenicinvolvement. Anatomic substages of Stage IIIA disease have been designated to differentiatebetween upper abdominal disease (III 1) and lower abdominal disease (III 2). A biologicdifference or prognostic significance has not been clearly shown with respect to 5-yearsurvival or disease-free survival between upper and lower abdominal involvement. 42 Both aclinical stage designation and a pathologic stage designation are implied by the Ann Arborstaging classification.Clinical stage is dependent on history and physical examination, the initial diagnostic biopsy,laboratory tests, and the results of radiographic and imaging studies. Pathologic stage is moreaccurate than the clinical stage because histopathologic data from the bone marrow, liver,

spleen, intra-abdominal lymph nodes, and other involved tissues (e.g. bone, skin, lung)provide precise knowledge of the extent of the disease.Lymphangiography and abdominal CT are reliable and complementary tests to evaluateretroperitoneal and abdominal nodal involvement. Lymphangiography has an overall accuracyof 80% to 90% with high sensitivity and specificity and can detect disease in nodes that arenot significantly enlarged. Shortcomings include the need for bipedal incisions and a failure toadequately visualize the celiac, splenic hilar, and portal nodes. These and other enlargedlymph nodes can be detected by CT, which has lower overall accuracy, sensitivity, andspecificity than lymphangiography. 42 CT is not helpful in detecting splenic involvementunless extensive splenic disease exists. 24, 25 When the lymphangiogram is positive,involvement of retroperitoneal nodes by Hodgkin's disease is confirmed by staginglaparotomy in 80% to 90% of cases. 24, 42 Additionally, approximately 40% of patients with

abnormal lymphangiograms have another site of Hodgkin's disease within the abdomen, mostcommonly the spleen. 24 A normal lymphangiogram usually indicates that the retroperitoneallymph nodes are uninvolved (10%15% incidence of false-negative results) but does notexclude other abdominal sites of occult disease. Approximately 20% of patients with negativelymphangiograms have intra-abdominal disease, usually in the spleen.


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Subdiaphragmatic Hodgkin's disease is frequently confined to the spleen and splenic hilarlymph nodes. The probability of subdiaphragmatic Hodgkin's disease is related closely tohistopathologic subtype, with mixed cellularity and lymphocyte depletion subtypes havinggreater likelihood of subdiaphragmatic extension than lymphocyte predominance and nodularsclerosis subtypes. The probability of splenic involvement increases with increasing spleensize and is almost always present in spleens weighing more than 400 gm. The absence ofsplenomegaly does not exclude splenic involvement. Hodgkin's disease involving the spleen iscommonly apparent on gross examination as grayish white nodules ranging from several

millimeters to several centimeters. Liver involvement with Hodgkin's disease rarely occurs inthe absence of splenic disease. Hepatic disease, in contrast to splenic disease, may not beapparent from inspection and palpation.In a report of the Stanford experience, the spleen was found to be involved with Hodgkin'sdisease in 39% of patients undergoing staging laparotomy. 42 In 50% of these, the spleenwas the only site of intra-abdominal disease detected by staging laparotomy. Splenicinvolvement consisted of fewer than five nodules in 27%, with all of the nodules being toosmall to have been detected by CT or found on random biopsy. All positive liver and accessoryspleen specimens were associated with positive splenic involvement, suggesting that thespleen is the trigger for visceral dissemination.Staging laparotomy, which in the past was frequently employed for pathologic staging ofHodgkin's disease, is now being used less frequently. Its use as a diagnostic test has been

based on the following:1. Hodgkin's disease generally begins in a single area and spreads initially in a predictableand nonrandom manner through lymphatic channels to contiguous lymph node areas andorgans having a prominent lymphatic tissue component.2. Selection of therapy is dependent on pathologic stage.3. Assignment of stage using clinical criteria alone is often inaccurate. Twenty-five to 30% ofclinically staged patients will have their stage of disease increased (upstaged), and 10% to15% will be downstaged after laparotomy for a total alteration in stage of approximately 40%.(Patients with AIDS who develop Hodgkin's disease have great likelihood of being upstaged bylaparotomy.)4. Prognosis is related primarily to the pathologic stage of the disease.

The role of staging laparotomy continues to be re-evaluated as a routine staging procedurefor Hodgkin's disease. Diagnostic advantages and contributions of staging laparotomy havehelped to significantly change the understanding and therapeutic management of patientswith Hodgkin's disease, and the current success and widespread use of combinationchemotherapy has challenged the need to know the precise anatomic extent of the diseaserequired for treatment by radiation therapy. 31 Staging laparotomy is not applicable to allpatients with Hodgkin's disease and should be performed only in patients in whom the resultsmay change management decisions and plans for therapy. Patients with advanced disease,clinical Stage IIIB or Stage IV, do not benefit from staging laparotomy because treatmentemploys combination chemotherapy. (If splenomegaly is present or develops in theseadvanced stages of Hodgkin's disease, splenectomy may be of value to control cytopeniasand reduce tumor burden.) Staging laparotomy has been restricted by the recognition of the

limitations of radiation therapy for patients with extensive mediastinal presentation or withmultiple extranodal sites. The success of combination chemotherapy in treating minimal oroccult disease and for controlling recurrent disease after radiation therapy is a majorconsideration in further restricting the use of staging laparotomy. 31 Splenectomy inHodgkin's staging has been shown to be a predisposing risk factor for acute leukemia inpatients older than 40 years of age who have received combination chemotherapy (MOPPmechlorethamine, vincristine, procarbazine, and prednisone). This surprising associationsuggests that staging laparotomy with splenectomy should not be done in patients of this agegroup who may eventually require MOPP-like chemotherapy.Controversy continues regarding the role of staging laparotomy, and improved noninvasivediagnostic tests and the introduction of more effective and less toxic chemotherapy continueto reduce the indications for this procedure. Currently, staging laparotomy is appropriate for

selected patients with Hodgkin's disease of low clinical stage (Stage IA, IIA, and IIIA) in whomthe results will have major influence on therapeutic management.Staging laparotomy is based on a systematic abdominal exploration with an organizedapproach to tissue sampling and consists of splenectomy, liver biopsy, and selective excisionof abdominal and retroperitoneal lymph nodes based on CT, lymphangiographic, and


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operative findings. The operation is performed through a midline incision. The liver isexamined initially, and if no gross evidence of disease is identified, a 2-cm. wedge of tissue isexcised from the left hepatic lobe, and deep biopsy samples are obtained from the right andleft lobes with a Trucut needle. Splenectomy is then performed with biopsy of splenic hilarlymph nodes and placement of identifying metal clips on the splenic pedicle. Partialsplenectomy does not provide an adequate degree of accuracy in staging to justify its use asan alternative to splenectomy. The lesser omentum is incised, and a lymph node is removedfrom the celiac axis region. The hilum of the liver, cystic duct, and distal common duct areas

are inspected, and representative lymph nodes are removed. Representative nodes areexcised from the small intestinal mesentery and mesocolon. Exposure of the para-aortic,paracaval, and iliac lymph nodes is necessary to adequately examine these areas. If anyabnormal or suspicious retroperitoneal nodes were demonstrated on the lymphangiogram,the nodes are excised and the sites are marked with metal clips. Confirmation that thespecific node or nodes have been excised can be obtained by comparing an intraoperativeabdominal radiograph with the lymphangiogram. Ten to 15% of patients with normallymphangiograms will have involvement of the retroperitoneal lymph nodes by Hodgkin'sdisease (false-negative), and representative nodes should be excised even if thelymphangiogram is normal. A bone marrow biopsy should be obtained from the iliac crest toconclude the staging aspects of the operation. Preoperative bone marrow biopsy has a false-negative rate of 2% to 3% and would constitute a significant treatment error if not corrected

by staging laparotomy findings.Oophoropexy (ovarian translocation) is advisable in the premenopausal woman in whomradiation therapy using an inverted Y port is likely. Both ovaries should be moved from thepotential field of radiation and identified with metal clips. Lead shielding is an importantadjunct to the protective effects offered by oophoropexy, and menstrual function is retainedin approximately 55% of women receiving pelvic irradiation for Hodgkin's disease afteroophoropexy and lead shielding. Ancillary procedures such as appendectomy orcholecystectomy add an unnecessary risk to the staging laparotomy and are notrecommended.Staging laparotomy has minimal morbidity, and the mortality rate is less than 0.5%. The riskof developing postsplenectomy sepsis in patients with Hodgkin's disease is 10% or higher.Current treatment of Hodgkin's disease integrates radiation therapy and combinationchemotherapy to achieve the maximum potential for cure. The success of combinationchemotherapy in controlling and even curing Hodgkin's disease in patients demonstratingrecurrence after radiation therapy has been a major therapeutic advance. In the Stanfordexperience from 1974 to 1980 for patients at all stages of Hodgkin's disease, survival was86%, and freedom from progression (FFP) was 77% in surgically staged patients. 42 Forpatients with Stage IA and IIA disease being treated by irradiation only, survival and FFP were91% and 82%, respectively, with no advantage being shown by adding chemotherapy (usuallyMOPP). Adding chemotherapy to radiation improved survival from 65% to 92% and FFP from70% to 82% in patients with Stage IIIA disease. Patients with Stage IIIB disease had agenerally poorer prognosis even with combination therapy, but alternating chemotherapy andradiation therapy has yielded significantly improved survival. Extensive extranodal disease

(Stages IIE, IIIE, IV) has a poor survival (approximately 60% at 5 years), whether irradiation orcombined therapy is used.Most patients with Hodgkin's disease present with Stage II or III disease. Ten to 15% presentwith Stage I or IV. Untreated Hodgkin's disease has a 5-year survival rate of 5%. Currentsurvival rates for Hodgkin's disease, however, approximate 85% for all stages. The goldstandard for the management of Stage I and IIA Hodgkin's disease is external-beam radiation.

The potential contribution of adjuvant radiation therapy to the management of advanced-stage Hodgkin's disease remains controversial. The cornerstone of therapy for advancedHodgkin's disease is combination chemotherapy. It is the staging between IIA and IIIA thatmight make some difference.

There are subsets of patients in whom the likelihood of any staging change that would altertherapy is remote. The risk of having abdominal involvement is less than 10% in women with

clinical Stage I disease, in men with clinical Stage I disease with lymphocyte predominance,and in women with clinical Stage II disease who are younger than 27 years of age with threedifferent sites of involvement. Alternatively, the patient with Stage I disease who has a largemediastinal mass now usually requires chemotherapy in addition to external-beam radiation,because of recurrence outside the radiation ports and the fact of cardiac, especially


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pericardial, complications from radiation. Patients with Stage IIIB disease require no staging,nor do ones with multiple E, IIA 2. Another contraindication or reason for the decline in staginghas been the appearance in significant numbers of patients of acute myeloid leukemia inpatients who have had MOPP therapy and have received staging laparotomy withsplenectomy.

The approximate results of different stages of Hodgkin's disease, then, are as follows: Stages Iand IIA treated by external-beam radiation alone have an 80% FFP (free from progression)and a 90% regression-free survival; Stage IIIA has a 94% relapse-free survival at 10 years with

MOPP; and Stage IVA with alternating MOPP and ABD has an 80% remission. The potential ofbone marrow transplantation adding to the treatment is an additional therapeutic maneuver.The reason, then, that staging laparotomies are less frequently done currently is not entirelydue to the ability to better stage the disease by noninvasive means (e.g., CT, laparoscopicsurgery). It in part results from the effectiveness of the various therapeutic modalitiesavailable. Salvage after recurrence is quite possible with most patients with Hodgkin'sdisease, making it less important that the small differential that would be changed from astaging process at the present time would make much difference in overall survival.

Non-Hodgkin's LymphomasNon-Hodgkin's lymphomas constitute a diverse group of primary malignancies oflymphoreticular tissue. The clinical course and natural history of NHL are more variable than

those of Hodgkin's disease, the pattern of spread is irregular, and more patients haveleukemic features. Current histologic classifications incorporate the nomenclature based onlight and electron microscopic morphology, histochemical studies, and selected cell-surfaceantigens. For prognostic and therapeutic purposes, NHL is classified according to nodular(favorable) and diffuse (unfavorable) types.In contrast to Hodgkin's disease, only about two thirds of patients with NHL initially haveasymptomatic lymphadenopathy. In 20% to 35% of patients, the onset of NHL occurs in anextranodal site. 3 In addition to peripheral and mediastinal lymphadenopathy, NHL iscommonly found initially as an abdominal mass (retroperitoneal or mesenteric) or as hepaticand/or splenic enlargement. Constitutional symptoms such as fever, weight loss, and nightsweats are frequently present. Occasionally the first manifestation of NHL is an oncologicemergency such as superior vena caval syndrome, spinal cord compression, or ureteralobstruction.In NHL the mode of spread generally is unpredictable, and most patients have disseminateddisease at the time of presentation.

In patients with initial nodal involvement, early spread may be limited to contiguouslymphatic sites or adjacent extranodal sites. More often, NHL spreads rapidly to distant nodaland extranodal sites through the bloodstream. Progression of NHL arising in extranodal areasmay be through (1) local invasion of adjacent structures, (2) extension to regional lymphnodes, and/or (3) dissemination to noncontiguous lymph nodes and/or distant extranodalsites. The extranodal spread of NHL is comparable to the pattern of metastasis observed incarcinoma. 3

The median age at the time of diagnosis is 50 years, without sex preference. Patients younger

than age 35 and older than 65 are more likely to have diffuse histology. The majority of NHLsare monoclonal B-cell tumors that are sometimes associated with an IgM or IgG protein. Insome patients, particularly children with a mediastinal mass, the disease is thymic.

As with Hodgkin's disease, chemotherapy and/or radiation therapy are the primary forms oftreatment. Therapeutic considerations are based on the histopathologic type of lymphomaand the stage (extent) of disease. Because the majority of patients with NHL havedisseminated disease at the time of presentation, staging laparotomy is seldom required andis indicated only for the patient with limited disease in whom laparotomy findings mayinfluence selection of therapy.NHL having primary presentation in the spleen may present as asymptomatic splenomegaly,with or without hypersplenism. Radionuclide scanning, CT, and magnetic resonance imaging

usually reveal nonspecific, featureless organ enlargement. If parenchymal expansionsecondary to tumor infiltration and congestion becomes massive, splenic pooling andincreased regional blood flow may result in hypersplenism. NHL with primary presentation inthe spleen may result in the diagnosis of idiopathic splenomegaly until splenectomy permitsaccurate histopathologic diagnosis.


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Splenectomy in NHL is also performed for hematologic depression secondary tohypersplenism or to relieve symptomatic splenomegaly or discomfort from recurrent splenicinfarctions. Hypersplenism may produce symptomatic anemia requiring red blood celltransfusions, dangerous levels of thrombocytopenia, and leukopenia with recurrent infections.

The severity of the cytopenia may require withholding of chemotherapy and radiationtherapy. Immunohemolysis or AIHA occasionally contributes to the anemia in NHL and isdiagnosed by a positive Coombs test.

The bone marrow typically has significant infiltration by neoplastic cells and additionally

shows erythroid hypoplasia and decreased megakaryocytes. Because most patients with NHLhave received chemotherapy or radiation therapy before becoming candidates forsplenectomy, the splenic contribution to the pancytopenia can only be determined by theresponse to splenectomy. 13 Almost all patients with NHL undergoing splenectomy forhypersplenism require red cell and platelet transfusions preoperatively.Significant therapeutic benefit can be achieved by splenectomy in 80% to 90% of patientswith advanced lymphomas (including Hodgkin's disease). Although patients with both NHLsand Hodgkin's disease may develop remission with reinstituted chemotherapy after correctionof cytopenias, the eventual outcome of the underlying disease is unchanged. Most patientswith well-differentiated lymphocytic lymphoma survive for 5 years, and many live 10 yearsafter the diagnosis is made. The prognosis is more favorable for the nodular than for thediffuse forms of NHL.

Chronic Lymphocytic LeukemiaChronic lymphocytic leukemia (CLL) is a lymphoproliferative abnormality that occurs primarilyin the elderly (sixth decade of life or older), with a male predominance (2:1). Proliferation andaccumulation of abnormal lymphocytes in lymphatic tissues result in the major signs oflymphadenopathy, splenomegaly, and lymphocytosis in the peripheral blood. The mostconstant abnormality on physical examination is lymph node enlargement, which frequently isfound either by the patient or on routine physical examination. Splenomegaly is present inmost patients and is progressive during the course of the disease. Hepatomegaly is a frequentfinding, and lymphocytic infiltration of the skin and gastrointestinal and respiratory tractsoccurs as the disease progresses. The diagnosis is based on the increase in the totalleukocyte count due to a large number of abnormal, small, immature lymphocytes. Bonemarrow examination demonstrates a variable and progressive degree of infiltration byabnormal lymphocytes. 23, 51

Therapy for CLL incorporates the judicious use of chemotherapeutic agents, corticosteroids,irradiation, and splenectomy. Although CLL is not cured by available therapeutic modalities,effective palliation is achieved in most patients, and many lead relatively normal lives. Thedisease progresses over 5 to 10 years with gradual increases in lymphadenopathy,splenomegaly, and hepatomegaly and development of weakness, weight loss, anemia, andthrombocytopenia. CLL is frequently complicated by development of immune hemolysis(AIHA), in which the hemolytic anemia is nearly always Coombs positive. If hemolysisbecomes severe and cannot be controlled by medical therapy, splenectomy is useful toameliorate the hemolytic process. As in NHL, splenectomy in chronic lymphocytic leukemia isperformed primarily for hematologic depression secondary to hypersplenism and for palliation

of symptomatic splenomegaly (Fig. 3611 Fig. 3611). Significant hematologic improvementoccurs after splenectomy in 80% to 90% of patients, but the natural course of CLL isunchanged. Unless another illness supervenes, death usually occurs from hemorrhage orinfection.

Chronic Myeloid LeukemiaChronic myeloid (granulocytic, myelocytic) leukemia (CML, CGL) is a myeloproliferativeabnormality characterized by marked elevation of the leukocyte count from myeloid cells inall stages of maturation and by neoplastic overgrowth of granulocytes in the bone marrow.

The incidence of CML increases with age and is more frequent in males than in females (ratio3:2). Splenomegaly is the most common physical finding, and sternal tenderness,lymphadenopathy, and hepatomegaly are frequently present. A unique chromosomal

abnormality designated the Philadelphia chromosome (Ph) occurs in 90% of patients withCML. Patients who are Ph-negative have an atypical course and a poorer prognosis thanpatients with CML who have the Ph chromosome.

Chemotherapy (busulfan, hydroxyurea), irradiation, radioactive phosphorus, andextracorporeal irradiation of the blood can control symptoms and most physical and


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laboratory abnormalities of CML during the chronic or treatable phase, which lasts from 1 to 4years. 23, 51 Development of myeloblastic crisis appears to be an intrinsic feature of CMLand indicates an accelerated or acute stage of the disease, which results in death frominfection or hemorrhage within 3 to 6 months.Splenectomy may be of benefit in selected patients during the chronic stage of CML to palliatesevere thrombocytopenia and/or anemia and to relieve pain from splenic infarctions ormassive splenomegaly. Splenectomy offers no benefit in delaying the onset of blastictransformation, improving the quality of life after the development of blastic crisis, or in

prolonging survival. 32Hairy Cell LeukemiaHairy cell leukemia (leukemic reticuloendotheliosis) is an uncommon form of leukemiacharacterized by pancytopenia, splenomegaly without significant lymphadenopathy, andcharacteristic mononuclear cells in the blood and bone marrow. The disease is more commonin males (ratio 4:1). The typical patient is a middle-aged man with moderate splenomegaly,absence of significant peripheral adenopathy, and variable hepatomegaly.Initial complaints among symptomatic patients are abdominal fullness or discomfort due tosplenomegaly, nonspecific symptoms of fatigue, weakness, and weight loss, easy bruisingfrom thrombocytopenia, or recurrent infections associated with leukopenia. In approximately25% of patients, splenomegaly and cytopenias are detected during a routine examination orduring evaluation for an unrelated illness.

HCL is characterized by the presence of malignant cells that have irregular, filamentouscytoplasmic projections on light microscopy that give the cells a hairy appearance. Thesurface projections are demonstrable by electron microscopy as broad-based, undulatingruffles and patches of short, blunt microvilli.A pancytopenia of moderate severity is present in approximately two thirds of patients at thetime of diagnosis. Hairy cells are frequently present in the peripheral blood and often accountfor a large proportion of the total white cell count. Demonstration in the hairy cells of tartrate-resistant acid phosphatase (TRAP) isoenzyme activity as a red reaction product is helpfulsupporting evidence for diagnosis. Although not required for diagnosis, the TRAP positivereaction product occurs in 90% to 95% of patients with HCL. Bone marrow biopsy permitsdefinitive diagnosis of HCL from characteristic morphology.

Ten to 15% of patients with HCL have an indolent course with a nearly normal life expectancyand require no specific therapy. These are usually elderly men who have minimalsplenomegaly, relatively few hairy cells in the blood, and asymptomatic neutropenia. Theremaining 85% to 90% require treatment because of one or more cytopenias resulting insymptomatic anemia requiring transfusions, thrombocytopenic bleeding, and repeatedinfections attributable to neutropenia. Pancytopenia develops from concurrent splenic poolingsecondary to infiltrative splenomegaly and bone marrow replacement with hairy cells.Symptomatic splenomegaly and recurring splenic infarctions are other indications for therapy.For the majority of patients who require some form of therapy shortly after diagnosis,splenectomy continues to be an early consideration. Splenectomy is most appropriate forthose patients with severe cytopenias, a large spleen, and patchy bone marrow infiltration. Itresults in rapid palliation, and almost all patients have hematologic improvement. Blood cell

counts return to normal in 40% to 50% of patients, with the response lasting for many yearsand almost half the patients requiring no further therapy.Patients with HCL having diffuse infiltration of the bone marrow, minimal splenomegaly, andsevere cytopenias gain only minor or short-term benefit from splenectomy and requireadditional therapy. In the past 5 years interferon alfa and pentostatin have been found to behighly effective systemic therapy for HCL. Randomized trials of interferon alfa versuspentostatin are in progress, both for newly diagnosed HCL patients and those patientspreviously having had splenectomy. Presently, interferon alfa remains the systemic therapy ofchoice, with pentostatin being indicated for patients with HCL that is refractory to interferonalfa. Splenectomy likely will continue to have a place in the sequential treatment of thosepatients with HCL requiring therapy.

SPLENECTOMY FOR ANEMIAHemolytic anemia results from an increase in the rate of red blood cell destruction. The adultbone marrow can produce red cells at six to eight times the normal rate, and hemolysis mustbe reasonably severe before laboratory or clinical evidence of anemia occurs. Diagnosticevaluation should include a detailed family history because many hemolytic anemias that


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improve after splenectomy have a hereditary basis. Congenital hemolytic anemias have adefect intrinsic to the red blood cell that may involve the cell membrane (hereditaryspherocytosis), cellular metabolism (pyruvate kinase deficiency, glucose-6-phosphatedehydrogenase deficiency), hemoglobin structure (sickle cell anemia), or hemoglobin chainsynthesis rates (thalassemia). Acquired hemolytic anemias have an extracorpuscular factorthat affects normal red cells. Chromium-51labeled red cell survival studies are sometimesuseful to confirm hemolysis and a shortened red cell life span and to determine sites of redcell destruction.

Clinical features include variable pallor related to the degree of anemia, mild, fluctuating jaundice, and splenomegaly. Pigment gallstones are common after childhood and mayproduce biliary tract symptoms. Valuable laboratory studies include serum direct and totalbilirubin and haptoglobin levels. Jaundice associated with hyperbilirubinemia resulting fromhemolysis is caused by an excess of unconjugated (free) bilirubin and is measured by anincrease in the indirect reacting fraction of bilirubin. The unconjugated bilirubin that is boundto albumin does not enter the urine, and indirect hyperbilirubinemia thus is not associatedwith biliuria. Reticulocytosis and bone marrow erythroid hyperplasia reflect increased red cellproduction. Red cell morphology is often abnormal, as is osmotic fragility. Red cells taggedwith chromium-51 demonstrate a shortened red cell survival.

Hereditary Spherocytosis

Hereditary spherocytosis is a relatively common, genetically determined red blood cellmembrane disorder that results in hemolytic anemia. The erythrocyte membrane defectresults from a deficiency in spectrin, a major component of the membrane skeleton that isthought to be responsible for the shape, strength, and reversible deformability of the redblood cell.The membrane abnormality leads to a gradual loss of red cell surface area, so that instead ofremaining a flexible biconcave disc, the red cell becomes small and spherical. Lackingadequate deformability to traverse the splenic microcirculation, spherocytes are trapped inthe splenic red pulp and are eventually destroyed by reticuloendothelial cells.Hereditar

Surgical Diseases Of the Spleen KSMU

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