Splenectomy for Hematologic Disease

The UCLA Experience with 306 Patients

GEORGE MUSSER, M.D.,* GARY LAZAR, M.D.,t WILLIAMRONALD W. BUSUTTIL, M.D., PH.D.*

Between 1956 and 1981, 306 splenectomies for hematologicdiseases were performed at the UCLA Medical Center. Of theseoperations, more than 75% were performed for therapeutic rea-sons to control anemia, thrombocytopenia, neutropenia, or painfulsymptoms of splenomegaly. Of the 65 patients who had idiopathicthrombocytopenic purpura, 77% showed an excellent response,and of the 39 patients who had hereditary spherocytosis, 90%responded. Other diseases with predictably good response rateswere autoimmune hemolytic anemias, Felty's syndrome, andhairy cell leukemia. Forty patients with Hodgkin's disease hadsplenectomies for diagnostic purposes the last 10 years. Theoverall morbidity and mortality were 24% and 6%, respectively,the most common complications being pneumonia, wound in-fections, and local postoperative bleeding, and the most commoncause of death being sepsis. The review supports the thesis thatin carefully selected patients, therapeutic splenectomy can havedesirable palliative effects and that diagnostic splenectomy hasa sufficiently low risk to warrant its consideration in patientswith Hodgkin's disease.

V AGUE REFERENCES to splenectomy have been notedin ancient Greek and Roman literature from more

than 2000 years ago. However, it was not until the mid-19th century that therapeutic splenectomies were per-formed for splenic enlargement. In the early part of thiscentury, the indication for splenectomy included variousanemias and leukemias.' In more recent years, splenec-tomy has been performed for a variety of hematologicconditions in which the spleen is felt to exert a destructiveeffect on blood cells, thereby causing thrombocytopenia,anemia, leukopenia, or a combination of these.5 Also,splenectomy has been extremely useful to define the extentof diseases, particularly in Hodgkin's disease andnonHodgkin's lymphoma.6,7We report herein a retrospective review of splenecto-

mies performed between 1956 and 1981 at the UCLACenter for the Health Sciences. This study reviews the

HOCKING, M.D.,t

From the Department of Surgery* and the Department ofMedicine,t UCLA Center for the Health Sciences, UCLA

School of Medicine, Los Angeles, California

indications for and evaluates the responses to splenectomyfor a wide variety of hematologic diseases at a universityhospital. In addition, we have assessed the morbidity andmortality associated with splenectomy for these diseases.

Materials and Methods

The patients who had splenectomy performed for he-matologic diseases at UCLA between 1956 and 1981 wereretrieved by computer from the Departments of MedicalRecords and Pathology. The medical records of thesepatients were then reviewed and the information obtainedwas submitted to the Biomathematics Department foranalysis.

All charts were examined for hematologic diagnosis,reason for splenectomy, preoperative and postoperativemedications, and complications, including death. Thespleen weight and the number of accessory spleens wereobtained from the pathology reports. Preoperative andpostoperative erythrocyte and platelet transfusions werenoted. Hematologic parameters were recorded at variousintervals after splenectomy for 1 year. To minimize falseconclusions, the highest hemoglobin, hematocrit, leu-kocyte count, and platelet count in 1 week prior to surgerywere taken as the preoperative values. The indicationsfor splenectomy in all patients were recorded as diagnostic,therapeutic (anemia, thrombocytopenia, neutropenia,symptoms of an enlarged spleen), or a combination ofthese. None of these patients had the Acquired Immu-nodeficiency Syndrome (AIDS) or the prodrome ofAIDS.

Response Criteria

Response to splenectomy was defined in terms of thedisease process for which therapy was directed. For those

40

Reprint requests: Ronald W. Busuttil, M.D., Ph.D., Department ofSurgery, UCLA Center for the Health Sciences, CHS 77-132, Los Angeles,CA 90024.

Submitted for publication: November 1, 1983.

TABLE 1. Characteristics of306 Patients Who Underwent Splenectomy for Hematologic Disease

Spleen WeightNumber with (grams)

Number of Mean Sex ComplicationsDiagnosis Patients Age M/F (%) Deaths Mean (Range)

Idiopathic thrombocytopenicpurpura (ITP) 65 35 (0.5-73) 0.3 14 (22) 1 (2%) 171 (26-660)

Hodgkin's disease 40 26 (5-57) 1.5 4 (10) 2 (5%) 349 (50-1698)Hereditary spherocytosis 39 15 (4-44) 0.8 2 (5) 0 430 (57-1500)Non Hodgkin's lymphoma 25 49 (7-76) 0.9 9 (36) 1 (4%) 573 (60-2050)Idiopathic hypersplenism 21 48 (5-74) 2.0 9 (43) 5 (24%) 798 (357-2050)Myelofibrosis 17 55 (30-72) 2.4 8 (47) 3 (18%) 1776 (205-5180)Felty's syndrome 16 56 (20-80) 0.6 3 (19) 0 766 (225-1250)Hairy cell leukemia 16 52 (32-68) 15.0 3 (19) 1 (6%) 1904 (319-5400)Autoimmune hemolytic

anemia 14 44 (16-67) 0.6 3 (21) 0 762 (175-2800)Chronic myelogenous

leukemia 9 49 (21-87) 3.5 5 (56) 3(33%) 2981 (1102-6040)Splenomegaly with portal

hypertension 9 44 (21-62) 0.1 4 (44) 0 862 (500-1830)Chronic lymphocytic

leukemia 7 62 (49-71) 2.4 5 (71) 0 2113 (685-5500)Other* 28 35 (1-77) 0.6 7 (25) 0 773 (120-3050)

Total 306 76 (25) 16 (5%)

* This category includes ill-defined myeloproliferative disorders (4),pure red cell aplasia (3), pyruvate kinase deficiency (2), thalassemia (2),aplastic anemia (2), splenomegaly without cytopenia (2), infectiousmononucleosis (2), congenital nonspherocytic hemolytic anemia (1),

patients with thrombocytopenia, a complete response was

defined as a mean postoperative platelet count greaterthan 100,000/ul. A partial response was defined as a mean

platelet count of 50,000 to 100,000/ul and no re-

sponse was defined as a mean platelet count of less than50,000/ul.

For those patients with neutropenia (absolute preop-

erative neutrophil count < 1,000/ul) a complete response

was defined as a mean neutrophil count that was at leasttwice that of the pretherapy value and was greater than1 500/ul.For those patients with anemia, response was defined

in one of three ways compared to preoperative values:

1. Decrease in the transfusion requirements by at

least 50%.2. Decrease in the mean reticulocyte count by at

least 50%.3. In those patients who received no transfusions a

mean postoperative hematocrit greater than the preop-

erative value and greater than 30%.

Morbidity and Mortality

Intraoperative bleeding was considered to be a com-

plication when the intraoperative blood administrationwas at least 3 units. Postoperative bleeding was considereda complication if it required the patient to return to theoperating room or if a wound hematoma was evacuated.

systemic lupus erythematosus (1), amyloidosis (1), sickle cell anemia(1), Letter-Siwi disease (1), Gaucher's disease (2), polycythemia vera (1),mast cell leukemia (1), subacute monocytic leukemia (1).

Postoperative pneumonia, wound infection, and intra-abdominal abscesses were recorded. Operative mortalitywas defined as any death occurring within 30 days ofsurgery.

Results

Patient Characteristics

There were 306 patients who underwent splenectomyfor hematologic diseases between 1956 and 1981 at UCLA(Table 1). Of the 149 men and 157 women, 95% werewhite Americans or had Spanish surnames and 3% wereBlack. There were 49 patients (16%) who were in thepediatric age group of 16 years or less. One hundred eight-five patients (60%) were in the adolescent and middle-aged group of between 17 and 60 years of age and 72patients (24%) were in the older age group of greater than60 years. The most common diagnoses among the groupof306 patients were idiopathic thrombocytopenic purpura(ITP) (65), Hodgkin's Disease (40), and hereditary spher-ocytosis (39). One hundred thirteen patients (36%) werefollowed for 1 year or more. The median follow-up timewas 3 months.The spleens weighed between 26 and 6200 grams; mean

spleen weights are shown according to the various diseasesin Table 1. Fifty-eight patients (19%) were found to havean accessory spleen, which was removed at the time ofsurgery. The highest incidence of accessory spleen was

41SPLENECTOMY FOR HEMATOLOGIC DISEASEVol. 200 * No. I

Ann. Surg. July 1984

TABLE 2. Reasons for Splenectomy and NumberofComplications in 306 Patients

Reason for NumberSplenectomy of Patients Complications

Diagnostic only 59 (19%) 10 (17%)TherapeuticOne indication 169 (55%) 36 (21%)Greater than one 78 (26%) 30 (38%)

There is a significant difference in the number ofcomplications betweenthe diagnostic and therapeutic groups (p = 0.001).

found in patients with hereditary spherocytosis (40%).Eighteen per cent of the patients with ITP were found tohave accessory spleens.

Splenectomies were performed for therapeutic reasonsin the majority of patients (76%) (Table 2). Nineteen percent of patients had splenectomy performed for diagnosticpurposes and only five per cent had splenectomy per-formed for both diagnostic and therapeutic reasons. Ofthe 247 patients who had splenectomy performed fortherapeutic reasons, the indications for splenectomy in-cluded anemia (44%), thrombocytopenia (45%), neutro-penia (15%), and symptoms ( 1%).

Diagnosis by Age Group

In the pediatric age group, 48% of splenectomies wereperformed for hereditary spherocytosis. The other com-mon indications for splenectomy in this age group in-cluded ITP (17%) and Hodgkin's Disease (13%). In theadolescent to middle-aged group the most common rea-sons for splenectomy were ITP (24%) and Hodgkin's dis-ease (13%). In the older age group ITP was the mostcommon diagnosis (17%), while idiopathic hypersplenismwas an indication in 15% ofpatients and Felty's syndromewas an indication in 12%.

Diagnosis by SexIn women ITP was more common as an indication

for splenectomy (77%). Hairy cell leukemia was an in-dication for splenectomy almost exclusively in men (94%).Staging of Hodgkin's Disease (60%), myelofibrosis withmyeloid metaplasia (71%), and chronic myelogenous leu-kemia (78%) were more common indications for sple-nectomy in men.

TABLE 3. Response to Splenectomy in 65 Patients withIdiopathic Thrombocytopenic Purpura

Mean Postoperative Platelet Count

<50,000/ul 50-100,000/ul >I00,000/ul(No (Partial (Complete

Response) Response) Response)

Number of patients 6 (9%) 9 (14%) 50 (77%)

TABLE 4. Response to Splenectomy in Patientswith Various Types ofAnemia

NumberDiagnosis of Patients Response

Hereditary spherocytosis 39 (30)* 26 (90%)Autoimmune hemolytic anemia 14 (12) 10 (83%)Idiopathic hypersplenism 15 (14) 10 (71%)Hairy cell leukemia 12 (9) 6 (67%)Myelofibrosis 15 (13) 7 (54%)

* Represents the number of patients with evaluable data.

Response to Splenectomy

Thrombocytopenia. All 65 patients with ITP had sple-nectomy performed for thrombocytopenia either becausethere was no response to glucocorticosteroids and/or cy-totoxic agents, or it was not possible to taper the glu-cocorticosteroids into a nontoxic range while maintainingan adequate platelet count. Table 3 shows the results ofall patients with ITP. A complete response was seen in77% ofpatients and a partial response in 14%. No responseoccurred in nine per cent of patients.Anemia. Table 4 shows the results of splenectomy per-

formed in patients with anemia as the primary indication.The response to splenectomy is related to diagnosis. Thehighest response rate was seen in patients with hereditaryspherocytosis (90%).

Granulocytopenia. Patients with hairy cell leukemiaand Felty's syndrome had splenectomy performed forgranulocytopenia (Table 5). The response to splenectomywas 71% and 83%, respectively.

Effect ofPreoperative Antibiotics on Postoperative Infec-tions

The effect of preoperative antibiotics on postoperativeinfections is shown in Table 6. This evaluation was per-formed retrospectively and not all patients received thesame antibiotic regimen. Therefore, the results must beviewed with caution. However, as can be seen, antibioticsdid not significantly alter the incidence of postoperativeinfections. In addition, there was no relationship betweenpreoperative neutropenia and postoperative infections.

ComplicationsThere were 118 postoperative complications in 76 of

the 206 patients (24%) (Table 7). Infections were the most

TABLE 5. Response to Splenectomy in Patients with Neutropenia

NumberDiagnosis of Patients Response

Felty's Syndrome 15 (12)* 10 (83%)Hairy cell leukemia 10 (7) 5 (71%)

* Represents the number of patients with evaluable data.

42 MUSSER AND OTHERS

SPLENECTOMY FOR HEMATOLOGIC DISEASE

common complications occurring in 14% of the entiregroup. Of all patients receiving preoperative steroids, 11%had postoperative wound infections, which is significantlygreater than the risk for the whole group (p = 0.001).Seventy-eight per cent of patients with wound infectionshad preoperative steroids. A disproportionate number ofwound infections occurred in patients who underwentsplenectomy for ITP (6/18).Pneumonia occurred in seven per cent of the entire

group. The highest incidence of pneumonia occurred inpatients with chronic lymphocytic leukemia (2/7) andpatients who had splenectomy performed for non-

Hodgkin's lymphoma (4/25). Pneumonia occurred withnearly equal frequency in patients who had splenectomyfor therapeutic and diagnostic purposes. Sepsis or intra-abdominal abscess occurred in 5 per cent of the entiregroup.

Bleeding complications occurred in 16 patients (5%).There were no bleeding complications ifsplenectomy wasperformed for diagnostic purposes. Patients with chronicmyelogenous leukemia (22%) and patients with myelo-fibrosis with myeloid metaplasia (12%) had the highestincidence ofintraoperative hemorrhage. Patients with ITPhad a five per cent risk ofdeveloping severe postoperativebleeding. Wound hematoma was an uncommon com-

plication (1%) for all patients. Two per cent of patientshad thrombotic complications.

There was a six per cent mortality associated with sple-nectomy for the entire group (Table 8). The most commoncause of death was sepsis, which occurred in 50% of pa-

tients who expired.

Discussion

The normal human spleen performs several importantphysiologic functions, the most important of which are:

(1) it acts as the main site of filtering microorganismsthat have invaded the circulation; (2) it acts as the majorsite of synthesis of specific (IgM) antibody; (3) it is a siteof hematopoiesis during fetal life; (4) it is the site of syn-

thesis of tuftsin and properdin, two proteins that serve

TABLE 6. The Effect ofPreoperative Antibiotics on PostoperativeInfections in 303 Patients

Preoperative No PreoperativeAntibiotics Antibiotics

Infection (N = 72) (N = 231)

Pneumonia 4 (6%) 16 (7%)Sepsis or abscess 4 (6%) 10 (4%)Wound 3 (4%) 15 (7%)Urinary 4 (6%) 8 (4%)Number of patients with

infections 10 (14%) 41 (18%)

There is no significant difference between the number of infectionsin these two groups.

43TABLE 7. Complication ofSplenectomy in 318 Patients

with Hematologic Diseases

Diagnostic Therapeutic WholeSplenectomy Splenectomy Group

Complication (N = 58) (N = 248) (N = 306)

BleedingIntraoperative 0 (0%) 7 (3%) 7 (2%)Postoperative 0 (0%) 13 (5%) 13 (4%)Wound hematoma 0 (0%) 2 (1%) 2 (1%)

InfectionPneumonia 4 (7%) 16 (6%) 20 (7%)Wound 2 (3%) 16 (6%) 18 (6%)Sepsis 1 (2%) 7 (3%) 9 (3%)Urinary 2 (3%) 7 (3%) 9 (3%)Intra-abdominal abscess 0 (0%) 7 (3%) 7 (2%)

Pancreatitis or Pancreaticfistula 0 (0%) 7 (3%) 7 (2%)

Thrombosis 0 (0%) 6 (2%) 6 (2%)

Other* 5 (9%) 16 (6%) 22 (7%)

Death 0 (0%) 18 (7%) 18 (6%)

* This category includes left pleural effusion (4), coagulopathy (4), renal failure(3), liver failure (3), pulmonary edema (3), wound dehiscence (1), small bowelobstruction (1), hepatic vein thrombosis (1), cardiac arrest (1), gastrointestinalhemorrhage (1).

as opsonins; and (5) it removes abnormal blood cellsfrom the circulation.8

However, under certain pathological conditions, thespleen can exert a destructive effect on hematopoieticelements, which is often referred to as "hypersplenism."Although "hypersplenism" is a relatively imprecise term,it usually refers to: (1) splenomegaly, (2) anemia, leu-kopenia, thrombocytopenia, or a combination of these,(3) compensatory bone marrow hyperplasia, and (4) im-provement after splenectomy.9Many hematologic diseases and syndromes cause hy-

persplenism. Removal ofthe spleen is performed for sev-eral of these conditions in an attempt to alleviate symp-toms.2-5 Besides traumatic injury, the other major reasonfor performing splenectomy is for the staging of hema-tologic diseases like Hodgkin's disease.6The complications of splenectomy can be divided into

those that occur early, which are usually postoperativeinfections and bleeding,'0 and those that occur late,most commonly associated with the effects of hypo-splenism. The most significant late complication of sple-nectomy is fulminant, often fatal, bacteremia, which mayoccur in children and adults.'21'4Most patients in this study (81%) had splenectomy

performed for therapeutic reasons. Nineteen per cent ofpatients had splenectomy performed for diagnostic pur-poses. Most of the patients in the latter group had Hodg-kin's disease and elective splenectomy was performed forstaging. Significantly fewer complications were observed

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Ann. Surg. * July 1984

TABLE 8. Deaths Due to Splenectomy

Age(Years) Sex Diagnosis Cause of Death

5 mo M Idiopathic thrombocytopenia purpura (ITP) Intracerebral hemorrhage47 F Chronic myelogenous leukemia (CML) Hemorrhage, sepsis51 F CML Sudden cardiac arrest54 M CML Sepsis49 F Myelofibrosis Gastrointestinal hemorrhage46 M Myelofibrosis Arrhythmia61 M Myelofibrosis Gastrointestinal hemorrhage38 M Hodgkin's disease Sepsis57 F Hodgkin's disease Gastrointestinal hemorrhage Liver failure63 F Idiopathic hypersplenism (IH) Arrhythmia, multisystem failure58 F IH Sepsis63 M IH Sepsis24 M IH Congestive heart failure, Pneumonia74 M IH Cardiac arrest38 M Hypersplenism, amyloidosis Sepsis64 F Gastric lymphoma Aspiration pneumonitis54 M Hairy cell leukemia Sepsis60 M Mast Cell leukemia Gastrointestinal hemorrhage

in the group undergoing diagnostic splenectomy (p0.001).The most common indication for splenectomy in our

study is ITP. Splenectomy is usually performed in thisdisease when there is a poor response to glucocorticoidadministration, or the dose of glucocorticoids necessaryto maintain an adequate platelet count is unacceptablyhigh.'5 The overall response to splenectomy was 91%,which is similar to the 65% to 88% response rate reportedby others.24"5'7 Despite severe thrombocytopenia inmany of these patients, only five per cent experiencedserious bleeding. One death was observed in 5-month oldbaby who expired with intracerebral hemorrhage. Thelow morbidity and mortality associated with splenectomyfor ITP have been similarly reported by others.15"17

Eighty-seven per cent of the patients in this study whounderwent splenectomy for congenital hemolytic anemiashad hereditary spherocytosis. In this disease, abnormalred cells are produced that are trapped and destroyed inthe spleen. Although splenectomy is not "curative" ofthe red cell defect, the complications of continuous he-molysis are prevented by this procedure. The results ofsplenectomy have been reported to be uniformly good.3'9" 4We report a 90% response rate with a very low morbidityand no deaths.

Acquired autoimmune hemolytic anemias may be id-iopathic or associated with other diseases.'8 The warm

antibody type is caused by IgG antibodies that usuallyare directed toward the Rh locus on red cells. The an-

tibody-coated red cells are sequestered in the spleen andthen destroyed. Glucocorticoid administration resultedin clinical improvement in 73% (8/11) of our cases. A73% response was seen after splenectomy, which is slightlyhigher than the overall response reported by others.'8"'9Anemia was the primary reason for splenectomy in

patients with myelofibrosis. Fifty-four per cent of ourpatients improved. However, there was a high morbidity(47%) (mostly bleeding) and an 18% mortality rate. Ben-bassat et al. reviewed 21 cases of splenectomy for my-elofibrosis and found a similar response rate and incidenceof complications.20 This high morbidity and mortalityhave been attributed to the advanced stage of diseasewhen splenectomy is performed in most patients.The other important disease for which anemia was the

reason for splenectomy was hairy cell leukemia. Similarto the experience of Little4 and Golomb and Vardiman,2'patients with hairy cell leukemia had a low complicationrate, despite their large spleens, and improvement in theirhematologic parameters.

Neutropenia was the primary indication for splenec-tomy in patients with hairy cell leukemia and Felty'ssyndrome. Although early splenectomy is indicated inhairy cell leukemia, controversy persists regarding theefficacy of splenectomy for all patients with Felty's syn-drome.22 We report a positive response of71% in patientswith hairy cell leukemia and 83% in Felty's syndrome.

Eighty-eight per cent of patients with Hodgkin's disease(35/40) had splenectomy performed for diagnostic rea-sons, and there were no complications or deaths in thisgroup. All of these staging procedures were done withinthe last 15 years, accounting for one of the major recentchanges in indications for splenectomy.6 Of the five pa-tients with Hodgkin's disease who had therapeutic sple-nectomy, 60% had complications and 40% died.

In children, hereditary spherocytosis and ITP rankedhighest among the hematologic indications for splenec-tomy, as have oeen reported by Kieswetter23 and Walker.24In Hong Kong, however, 62% of the therapeutic sple-nectomies in children were done for thalassemia.5 Onlytwo patients with thalassemia had splenectomy performed

MUSSER AND OTHERS44

Vol. 200 * No. I SPLENECTOMY FOR HEMATOLOGIC DISEASE 45

at UCLA. This difference obviously reflects the differencein the populations at risk.The overall incidence ofaccessory spleens in this review

(19%) is similar to the 11% to 20% incidence reportedby others.4"7'25 However, we found an extraordinarilyhigh incidence of accessory spleens in patients with he-reditary spherocytosis (40%). Lau found a 27% incidencein this disease in Hong Kong,5 and Olsen and Beaudoinfound a higher incidence of accessory spleens in hema-tologic diseases in general.26 Mintz et al. found that 40.9%of children and 22.4% of adults with ITP had accessoryspleens.'5 The importance of removing accessory spleensduring splenectomy for hematologic diseases is obviousfrom reports of a poor response if an accessory spleen isleft intact.'5We observed an overall morbidity of25% and mortality

of 28%. Others have reported complications in 13% to49% and mortality in 6% to 27% of patients.3 5 ' 1,24,25,27Overwhelming postsplenectomy infections have been re-ported both in children and adults. 12-14,28 The patientsin our study group were not followed long enough toassess the possibility ofthis often fatal complication. Vac-cination with polyvalent pneumococcal vaccine has beenreported to partially or completely prevent this compli-cation in patients undergoing splenectomy.29 It is currentlythe standard practice at UCLA that all patients receivevaccination -prior to operation.

AcknowledgmentThe assistance of Lee Youkeles of the Biomathematics Department

in the preparation and analysis of the data is greatly appreciated.

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mortality and end results. Ann Surg 1928; 88:409-415.2. Ly B, Albrechtsen D. Therapeutic splenectomy in hematologic dis-

orders. Acta Med Scand 1981; 209:21-29.3. Laws HL, Burlingame MW, Carpenter JT, et al. Splenectomy for

hematologic disease. Surg Gynecol Obstet 1979; 149:509-512.4. Little JM. A prospective study of 100 splenectomies. Aust NZ J

Surg 1978; 48:390-397.5. Lau JTK, Saing J, Wong J, Ong GB. Splenectomy in children in

Hong Kong. Aust NZ J Surg 1980; 50:589-593.

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7. Sweet DL, Kinzie J, Gaeke ME, et al. Survival of patients withlocalized diffuse histiocytic lymphoma. Blood 1981; 58:1218-1223.

8. Eichner ER. Splenic function: normal, too much and too little. AmJ Med 1979; 66:311-320.

9. Ellis LD, Dameshek HL. The dilemma of hypersplenism. Surg ClinNorth Am 1975; 55:277-285.

10. Albrechtsen D, Ly Bernt. Complications after therapeutic splenec-tomy for hematologic diseases in adults. Acta Chir Scand 1980;146:577-581.

11. Wolloch Y, Dagan R, Dintsman M. Complications ofsplenectomy.Isr J Med Sci 1980; 16:655-658.

12. Krivit W, Giebink GS, Leonard A. Overwhelming postsplenectomyinfection. Surg Clin North Am 1979; 59:223-233.

13. Krivit W. Overwhelming postsplenectomy infection. Am J Hematol1977; 2:193-201.

14. Sekikawa T, Shatney CH. Septic sequelae after splenectomy fortrauma in adults. Am J Surg 1983; 145:667-673.

15. Mintz SJ, Petersen SR, Cheson B, et al. Splenectomy for immunethrombocytopenia purpura. Arch Surg 1981; 116:645-650.

16. Karpatkin S. Autoimmune thrombocytopenic purpura. Blood 1980;56:329-343.

17. Schwartz SI, Hoepp LM, Sachs S. Splenectomy for thrombocyto-penia. Surgery 1980; 88:497-506.

18. Axelson JA, LoBuglio AF. Immune hemolytic anemia. Med ClinNorth Am 1980; 64:597-606.

19. Bowdler AJ. The role ofthe spleen and splenectomy in autoimmunehemolytic disease. Semin Hematol 1976; 13:335-348.

20. Benbassat J, Penchas S, Ligumski M. Splenectomy in patients withagnogenic myeloid metaplasia: an analysis of 321 published cases.Br J Haematol 1979; 42:207-214.

21. Golomb HM, Vardiman JW. Response to splenectomy in 65 patientswith hairy cell leukemia: an evaluation of spleen weight andbone marrow involvement. Blood 1983; 61:349-352.

22. Joyce RA, Boggs DR, Chervenick PA. Neutrophil kinetics in Felty'ssyndrome. Am J Med 1980; 69:695-702.

23. Kiesewetter WB. Pediatric splenectomy. Surg Clin North Am 1975;55:449-460.

24. Walker W. Splenectomy in childhood: a review in England andWales, 1960-1964. Br J Surg 1976; 63:36-43.

25. Eraklis AJ, Filler RM. Splenectomy in childhood: a review of 1413cases. J Pediatr Surg 1972; 7:382-388.

26. Olsen WR, Beaudoin DE. Increased incidence of accessory spleensin hematologic disease. Arch Surg 1969; 98:762-763.

27. Traetow WD, Fabri PJ, Carey LC. Changing indications for sple-nectomy. Arch Surg 1980; 115:447-451.

28. Eraklis AJ, Kevy SV, Diamond LK, Gross RE. Hazard of over-whelming infection after splenectomy in childhood. N Engl JMed 1967; 276:1225.

29. Ammann AJ, Addiego J, Wara DW, et al. Polyvalent pneumoooccal-polysaccharide immunization ofpatients with sickle-cell anemiaand patients with splenectomy. N Engl J Med 1977; 297:897-900.