Compelling Splenectomy in Medically Compromised Patients

JAMES J. BERGIN, M.D., COLONEL, MC, THOMAS F. ZUCK, M.D.,LT COLONEL, MC, ROBERT E. MILLER, M.D., COLONEL, MC (RET.)

THE VALUE OF SPLENECTOMY in hematologic disordershas been established.2372123 Benefit has been re-

ported in hypoplasia,13 acute idiopathic thrombocyto-penia,8 chronic idiopathic thrombocytopenia,28 myeloidmetaplasia,9'1'15"7 Felty's syndrome,4"9 lymphoma,18,20,24 and leukemia.6'22'25'26 The indications for splenec-tomy are not the subject of this clinical study. Rather,the practicality of the procedure is assessed in an unusualclinical setting in which splenectomy was deemed neces-sary for survival in the medically compromised patient.This approach is exemplified by Crosby, et al.,5 with theapplication of splenectomy to the elderly patient.Between September, 1965 and March, 1971, splenec-

tomy was performed in 15 patients characterized by (a)a hematologic malignancy o;r an autoimmune disorderand (b) life-threatening cytopenia. The majority hadbeen treated with prednisone and immunosuppressiveagents. These circumstances define the patient groupingand lead us to consider them as medically compromised.They are poor risks on the basis of underlying disease,serious thrombocytopenia or hemolytic anemia, and pre-vious immunosuppressive therapy. Thus, the hazards ofmajor surgery, such as infection, hemorrhage, and deathmust be carefully weighed against the potential gain ofuseful life.The hematologic malignancies included 5 patients with

Hodgkin's disease, all of whom were Stage 4-A or B.There were 3 with chronic granulocytic leukemia withone having entered an accelerated phase of the disease.Two patients suffered from smoldering granulocytic leu-kemia (pre-leukemia) and both eventually manifestedacute granulocytic leukemia. Of the autoimmune pa-tients, 3 suffered systemic lupus erythematosus and one

Submitted for publication September 25, 1972.Reprint requests: Medical Library, Fitzsimons General Hos-

pital, Denver, Colorado 80240.

From the Departments of Medicine and Pathology,Fitzsimons General Hospital, Denver, Colorado 80240

autoimmune hemolytic anemia. There was one patientwith idiopathic aplastic anemia who could be consideredto fall into either category, depending upon etiologicbias.

In regard to the life-threatening cytopenia, 14 of the15 had severe thrombocytopenia. All 14 patients hadskin, mucous membrane, or gastrointestinal bleeding.Thirteen patients required preoperative platelet supportor intensive prednisone therapy. One patient did not havethrombocytopenia but severe autoimmune hemolyticanemia which had relapsed after prednisone. Nine pa-tients had received prednisone or a similar drug, and 7,some of whom also had steroids, had taken other im-munosuppressive therapy. Three patients with Hodgkin'sdisease had been given radiotherapy. The ages rangedfrom 19 to 67, with a mean age of 35 years.

Case Reports

Case No. 1, J. C. This 42-year-old female was noted to havesplenomegaly, white count of 140,000, and bone marrow examina-tion consistent with chronic granulocytic leukemia seven yearsbefore admission. Intermittent busulfan therapy maintained a

relatively normal white count. She was admitted with a 4-monthhistory of generalized bone pain. The spleen was 6 cm belowthe left costal margin, WBC 33,000, with 3's blast forms, platelets54,000, and Hct 33. After allopurinol 100 mg q.i.d. and 6-mer-captopurine 50 mg daily for one week, she became asymptomaticwith a WBC of 10,000, platelets 2,000, and Hct 25. Bone marrow

aspirate was hypercellular with a profusion of imnmature granulo-cytes and decreased megakaryocytes. After one week of platelettherapy, an antibody unresponsive to 100 mg of daily prednisonewas encountered, and splenectomy was performed on September9, 1967. Hemostasis was assured with 500 cc of platelet-richpacked cells, four units of platelet concentrate, and three units ofplatelet-rich plasma. The postoperative course was complicated

761

BERGIN AND OTHERSby a supraventricular tachycardia and hypotension. Bone marrow

section was hypocellular with predominant early granulocytic

cells. The patient was discharged with a Hct of 27, WBC 2,700,

and platelets 31,000 on 6-mercaptopurine and allopurinol. She

was readmitted three months later severely thrombocytopenic re-

quiring a total of 182 platelet infusions until her death one month

later of leukemia and diffuse hemorrhage.

Comment. This patient entered an accelerated phase of

chronic granulocytic leukemia after seven years of intermittent

busulfan. Splenectomy was performed because of an acquired

platelet antibody which compromised platelet therapy. Initial

platelet therapy was deemed necessary to determine the potential

of a remission of acute leukemic transformation. Major surgery

can be performed in this type of patient but it is questionable that

this approach is warranted in view of the extremely low remission

rate accomplished in blastic transformation of long-standing

chronic granulocytic leukemia.

Case No. 2, E. S. This 26-year-old pregnant female noted

a rash on her arms and legs 5 months before admission. Biopsy

was consistent with discoid lupus erythematosus. She subsequently

developed arthritis with severe thrombocytopenia and bleeding

from the gums, nose, rectum, and into the urine. LE preparations

were positive. Bone marrow biopsy revealed ample megakaryocytes

and mild plasmacytosis. She was placed on 60 mg daily of oral

prednisone and intermittent platelet therapy. Suboptimal platelet

survival prompted intensified therapy of 30 mg of dexamethasone

and 250 mg of 6-mercaptopurine without alteration of transfused

platelet survival.On referral, physical examination showed a gravid female with

a diffuse maculopapular rash and multiple ecchymoses. The Hct

was 36, WBC 12,700, and platelets 4,000. Eight units of platelets

were administered before spontaneous delivery of a normal male.

Following delivery, splenectomy was performed. Her postopera-

tive course was complicated by left lower lobe pneumonitis. For

5 days, 156 units of platelets were transfused as a continuous

infusion to maintain a platelet count of 15,000 to 20,000. Bv

the sixth postoperative day, the platelet count had risen to 175,000

and steroids were discontinued over three days. On discharge,

the Hct was 32, WBC 7,900, and platelets 140,000. She has

remained well except for arthralgias responding to indomethacin

with a platelet count of 750,000.

Comment. This patient, while pregnant, converted from dis-

coid lupus erythematosus to disseminated as manifested by

arthritis, positive LE preparations, and severehemorrhagic throm-

bocytopenia unresponsive to high dosage of corticosteroids and

6-mercaptopurine. Platelet therapy, initially successful in stanching

hemorrhage, was compromised by a platelet antibody. Splenectomy

was complicated by a left lower lobe pneumonitis and a remark-

able postoperative requirement for 156 units of platelets. This case

illustrates not only the value of splenectomy in thrombocytopenia

secondary to lupus erythematosus but also the importance of

preoperative platelet preparation and the necessity of postoperative

maintenance when recovery is delayed.

Case No. 3, B. T. A 20-year-old gravid female noted multiple

ecchymoses and recurrent nosebleeds one month before admission.

Platelet count was 8,000 and bone marrow examination revealed

ample megakaryocytes. A transient rise in platelets to 38,000

after 100 mg daily of oral prednisone was followed by severe

thrombocytopenia, necessitating platelet transfusions for delivery

of a mature thrombocytopenic male.

Admission examination showed subsiding ecchymoses and a

poorly healing episiotomy. Hct was 34, white count 8,000, and

platelets 20,000. Splenectomy was performed on December 29,

1969 with platelet infusion support. Platelet survival did not

improve and 190 units of platelets were given as a continuous

infusion over the next five days. Her platelet count reached100,000, platelet infusion was discontinued, and steroids abruptlystopped. Nine days postoperatively, the patienit was treated ap-propriately for an Addisonian crisis. Because of concomitantthrombocytopenia, hemorrhage necessitated further platelet in-fusions. She then bled from ulcerations of the terminal ileum,requiring resection of the involved segment. Coagulation studiesrevealed an inhibitor to factors VIII and IX. An ileostomy andcolocutaneous fistula were constructed due to disruption of theanastomotic site. The patient died of E. coli peritonitis and septi-cemia 2 months after admission.Comment. The patient developed severe hemorrhagic throm-

bocytopenia minimally responsive to prednisone during the lastweeks of her pregnancy. Delayed platelet response to surgerynecessitated intensive platelet infusion postoperatively to a totalof 190 units. The abrupt cessation of prednisone after two monthsof therapy was ill-advised. Further, the surgical procedure per-formed for ileal ulcerations' with bleeding should not have beenprimary resection. In a patient on high dosage prednisone, ilealexteriorization might have prevented the subsequent anastomoticdisruption. The splenic histology, namely white pulp reticulumcells, severe thrombocytopenia, and coagulation inhibitors of VIIIand IX strongly suggest the diagnosis of systemic lupus erythe-matosus.

Case No. 4, A. F. This 23-year-old male noted right cervicallymphadenopathy 3 years prior to admission. Biopsy revealedHodgkin's disease and mantle therapy with extension to periaorticnodes was delivered to 3,900 rads. Two years later, he notedfatigue and weight loss. Lymphangiography suggested positivepelvic nodes and 2,000 rads were delivered to an inverted Y.Because of progressive thrombocytopenia to 49,000 and hemolyticanemia of Hct 23, chromium red cell half-life of 17 days, andsplenomegaly, a splenectomy was performed on April 4, 1969.The postoperative course was uneventful with a hematologicresponse of platelets to 478,000 and Hct 40. He returned toemployment and one year later was begun on sequential, andthen multiple chemotherapy because of systemic symptoms.He died of disseminated Hodgkin's disease 30 months aftersplenectomy.

Comment. The indication for splenectomy was progressivethrombocytopenia and anemia. He returned to full employmentafter a gratifyinghematologic response. In the latter stages ofhisdisease, chemotherapy was employed until his death from dis-seminated Hodgkin's disease.

Case No. 5, D. N. This 21-year-old male was referred fora left pleural effusion and fever of 6 weeks duration. Petechiaewere present on both lower extremities. The platelet count was

3,000 and a bone marrow section revealed megakaryocytichyper-plasia. Coagulation data showed an inhibitor to factors VIII andIX. Multiple ANA and LE determinations were negative. Onehundred mg prednisone was begun and eight units of plateletconcentrate given until the platelet count rose to 50,000 andbleeding ceased. Repeated attempts to decrease the prednisonedosage resulted in thrombocytopenia. Accordingly, the prednisonewas returned to 60 mg per day until the factor VIII and IXinhibitors were controlled and the platelet count retumed tonormal. After 5 months of therapy, the spleen was removedand the postoperative course was uneventful. After prednisonewas discontinued, the platelet count was 850,000 and the factorVIII and IX inhibitors were no longer present. After 18 monthswithout steroids,he remained asymptomatic with a normal plateletcount, coagulation studies, and LE preparations.Comment. The patient presented with systemic symptoms,

left pleural effusion, inhibitors to factors VIII and IX, and pro-gressivehemorrhagic thrombocytopenia, consistent with the diag-

762 Ann. Surg. * Dec. 1973

COMPELLING '

nosis of systemic lupus erythematosus. Massive doses of predni-sone controlled the platelet count and bleeding tendency, butdecrements in dosage were accompanied by a precipitous dropin circulating platelets. A sustained rise of platelets to 850,000ensued after steroids were discontinued and remained at 600,000after 18 months. The patient has remained well and gainfullyemployed.

Case No. 6, H. H. This 35-year-old male was referred forevaluation of splenomegaly. WBC was 190,000, with a differentialcount and bone marrow section consistent with chronic granulo-cytic leukemia. Hct was 35 and platelets 440,000. Busulfan was

started at 0.1 mg/Kg, accomplishing a WBC of 10,000, platelets200,000, and Hct 45. Treatment was discontinued, but twomonths later WBC was 2,000, Hct 23, and platelets 4,000. Platelettransfusions were instituted because of the severe thrombocytopeniaand purpura. A striking decrease in transfused platelets in spiteof steroids prompted consideration of splenectomy. Bone marrow

section demonstrated severe hypoplasia and moderate fibrosis.The postoperative course was complicated by a wound hematomaand abscess culturing Staph. aureus and recurrent pancreatitis.One month later, the patient was discharged without symptoms,with a Hct of 32, platelets 34,000, and WBC 7,400. After 2months, his peripheral blood returned to normal values and he

was placed on maintenance 6-mercaptopurine for control of histotal white count. For the next 20 months, he was gainfully em-

ployed prior to death from blastic crisis.Comment. Profound thrombocytopenia and generalized skin

and mucous membrane hemorrhage necessitated platelet support.Splenectomy was performed when decreased infused plateletsurvival, unresponsive to corticosteroids, ensued. This patientshould be contrasted with Case No. 1 in whom splenectomy was

performed during the accelerated phase of chronic granulocyticleukemia. This patient recovered a normal platelet level andwas employed full time for 20 months.

Case No. 7, M. H. This 50-year-old male presented 8 yearsbefore admission with fatigue, low grade fever, and splenomegaly.Total WBC of 85,000 and bone marrow aspiration were consistentwith chronic granulocytic leukemia. After busulfan therapy, he

became asymptomatic with normal physical examination andperipheral blood. For 2 years before admission, he received 2 mgbusulfan maintenance weekly. He was admitted for evaluaionof thrombocytopenia. Physical examination was normal withWBC of 8,000, Hct 40, and platelets 8,000. Bone marrow sectionrevealed granulocytic hyperplasia, decrease in megakaryocytes,normal erythrocytes, and no myelofibrosis. A Philadelphia chro-mosome was obtained from the marrow aspirate. Busulfan was

discontinued and 20 mg prednisone and 40 mg fluoxymesteroneadministered orally daily. Within one month, he developed in-sulin-dependent diabetes mellitus with a striking decrease invisual acuity. When daily platelet counts dropped below 20,000,platelet therapy was begun with encounter of a platelet antibodyin seven days. On October 16, 1967, splenectomy was performedwith platelet component support. Microscopic examination of thespleen was consistent with chronic granulocytic leukemia. Thepostoperative course was complicated by a left lingular pneu-

monitis. Steroids and fluoxymesterone were discontinued. He was

asymptomatic at discharge and two months later the WBC was

11,000, Hct 40, and platelets 400,000. He has remained welland employed for five years, receiving intermittent 6-mercapto-purine for control of the white count.Comment. This case is remarkable for the long survival of

chronic granulocytic leukemia. However, severe thrombocyto-penia related to an unusual sensitivity to busulfan became life-threatening. Discontinuance of prednisone abolished the diabetesand visual difficulty. Intermittent chemotherapy has maintained

SPLENECTOMY 763

a relatively normal white count. He has been asymptomatic andemployed for five years.

Case No. 8, A. T. This 39-year-old male first noted rightinguinal adenopathy 7 years prior to admission. Biopsy was inter-

preted initially as Hodgkin's disease but, on review, was readas reactive hyperplasia. A recurrence in the same area was

biopsied three years before admission and interpreted as lympha-denitis. Six months before referral, he complained of weightloss and fever. Hepatosplenomegaly and lymphadenopathyprompted a left axillary node biopsy. Hodgkin's disease was diag-nosed. Two courses of MOPP (mustargen hydrochloride, vin-cristine sulfate, prednisone, and procarbazine hydrochloride) were

administered with resultant severe and persistent pancytopenia.Hct was 25, WBC 1,800, and platelets 12,000. Bone marrow

biopsy revealed panhyperplasia. The postoperative course was

complicated by a staphylococcal pneumonitis and septicemia.Hodgkin's disease histologically involved the liver, spleen, andabdominal lymph nodes. Hematologic improvement occurred afterthe postoperative complications abated. The Hct was 35, WBC16,000, and platelets 130,000i one month after a single course

of MOPP. Hydroxyurea was then administered for 2 days. Hedied 5 months subsequent to surgery without significant remission.

Comment. Repeated biopsies for years prior to admissionwere suggestive, but not diagnostic of Hodgkin's disease. Whenthe diagnosis was established, he was staged as 4-B and begunon MOPP therapy. Optimal therapy was compromised by severe

persistent cytopenia and splenectomy was performed in the hopeof improving tolerance to chemotherapy.16 The bone marrow

was hyperplastic and compatible with hypersplenism. Hematologicimprovement allowed a course of MOPP and two days of hydroxy-urea. The surgery was successful in that the desired response ofelevation of blood elements occurred. The patient died of dis-seminated Hodgkin's disease with extensive hepatic involvement.

Case No. 9, C. D. This 37-year-old male was given 2,880 radsto left cervical Hodgkin's disease 14 years before admission. Be-cause of systemic symptoms and a positive abdominal lymph-angiogram, similar dose radiation wvas administered eight years

later to periaortic, inguinal, and mediastinal portals. Feverrecurred six months prior to admission and physical examinationrevealed right cervical adenopathy and splenomegaly. Pancyto-penia was treated by 60 mg of daily prednisone. There was a

transient rise in all blood elements. On referral, the right cervicaladenopathy and splenomegaly were apparent. Bone marrow

section revealed fibrosis, Hodgkin's disease, and erythroid hyper-

plasia. The platelet count was 65,000, Het 27, and WBC 8,600.Splenectomy was performed with increase of platelet count to220,000. The spleen demonstrated Hodgkin's disease and extra-medullary hematopoiesis. Abdominal nodes revealed Hodgkin'sdisease. He was discharged on chemotherapy and lived for 18months before dying of his basic disease.Comment. This patient received radiotherapy prior to his

admission for splenomegaly, anemia, and thrombocytopenia. Be-cause of cytopenia unresponsive to prednisone, the spleen was

removed without complication. His platelet count returned tonormal and the hematocrit to acceptable levels. He toleratedsequential chemotherapy for the remaining 18 months of his life.

Case No. 10, W. M. This 35-year-old male had right cervicalnode biopsies nine and 4 years prior to admission for asymptomaticlymphadenopathy. On both occasions, no evidence of malignancywas noted. Another biopsy from the same area was diagnosed as

Hodgkin's disease and treated with 3,000 rads to a mantle dis-tribution three years before referral. Because of symptomaticCoombs' positive anemia and splenomegaly six months prior to

admission, he was given 60 mg of prednisone. A partial remission

ensued but was complicated by overt diabetes mellitus. On ad-

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BERGIN AND OTHERS

mission, pallor and splenomegaly were noted. Peripheral bloodvalues were Hct 20 with a brisk reticulocytosis, WBC 4,800, andplatelets 53,000. Bone marrow section revealed erythroid hyper-plasia, myelofibrosis and Hodgkin's disease. Splenectomy was

performed with a benign postoperative course. Prednisone was

discontinued in one month. The spleen contained myeloid meta-plasia and Hodgkin's disease. Postoperative Hct was 34, WBC6,000, and platelets 920,000. He subsequently returned to hisoccupation and two years later required chemotherapy for sympto-matic Hodgkin's disease. He died 9 months later of disseminatedherpes zoster and esophageal and pulmonary moniliasis.Comment. Prednisone therapy not only failed in inducing a

remission of a disabling Coombs' positive hemolytic anemia, butwas complicated by symptomatic diabetes mellitus. Splenectomywas followed by a functioning hematocrit and normal plateletcount. After prednisone was discontinued, blood sugar determina-tions became normal. The patient remained well for over twoyears when sequential chemotherapy was instituted for symptom-atic Hodgkin's disease. Of interest was absence of demonstrableHodgkin's disease at autopsy.

Case No. 11, G. G. This 67-year-old male had noted a paularpruritic rash of the face and neck resistant to topical therapyfor 5 years. Biopsy revealed a mononuclear cell infiltrate. Pancyto-penia had progressed over 2 years. Two months previous to admis-sion, he developed severe purpura following an upper respiratoryinfection. No platelets could be found on blood smear. He spon-taneously recovered to the admission level of 42,000 platelets,Hct 30, and 2,800 WBC. Except for the papular rash and paleness,physical examination was normal. Bone marrow was panhyper-plastic with megaloblastic erythroid hyperplasia and increasedgranulocytic precursors with poor maturation. The marrow was

unresponsive to parenteral B-12 or folic acid. The diagnosis was

chronic myeloproliferative disease, with probable smoldering acutegranulocytic leukemia. Splenectomy was performed and his post-operative course complicated by left lower lobe pneumonitis anda left flank hematoma. The maximum hematologic response, one

month later, was 166,000 platelets, 7,000 WBC, and Hct 40.Within 3 years, his blood element values gradually assumed pre-splenectomy levels, although, in spite of infections, he had no

further platelet crises. Six years after splenectomy, he was placedon anti-leukemic therapy for blatant acute granulocytic leukemiawith a WBC of 120,000, the majority of which were blast forms.

Comment. Even though the diagnosis of smoldering granulo-cytic leukemia was thought relatively secure, splenectomy was

performed. Moderately severe thrombocytopenia had acceleratedinto a severe purpuric crisis with platelets absent on peripheralblood smear. His age of 67 and his demonstrated platelet crisiswith infection were considered indications for splenectomy. Inspite of recurrent bacterial and viral infections over the next sixyears, his platelet count never dropped below 35,000 and he

has led a normal existence until his leukemia recently becameaccelerated.

Case No. 12, M. B. For 2 years, this 46-year-old female was

known to have a progressive pancytopenia and a hypoplasticbone marrow. Purpura, epistaxis, and gingival bleeding occurredintermittently for one year with a recent exacerbation promptingadmission. Except for extensive purpura, her physical examinationwas normal. The platelet count was 13,000, Hct 31, and WBC2,700. Bone marrow biopsy was bypoplastic with a granulocyticlineage of smoldering granulocytic leukemia. Splenectomy was

performed, with preoperative and operative infusion of platelets.Her course was complicated by left lower lobe pneumonitis. Herhematologic improvement was modest with a platelet count of60,000, Hct 40, and WBC 7,000. She returned to a normal lifeuntil 26 months later, when symptomatic anemia necessitated

intermittent blood transfusions. Thirty-one months post-splenec-tomy, acute granulocytic leukemia, unresponsive to therapy, be-came manifest and she died of hemorrhage.

Comment. The patient was observed for 2 years for progressivepancytopenia. Because of severe hemorrhagic thrombocytopenia,a splenectomy was performed with full consideration of the diag-nosis of smoldering granulocytic leukemia. It was recognized thatthe megakaryocytes were greatly reduced in number, but a modestincrease in circulating platelets rendered her asymptomatic. Forover 2 years, she pursued a normal life until her leukemiaexacerbated.

Case No. 13, M. M. Fourteen days prior to admission, a19-year-old male complained of pain in a wisdom tooth. Extrac-tion was carried out the next day complicated by chills andfever persisting until three days before hospitalization. The Hctwas 25, platelets 20,000, and WBC 2,000. On admission, thephysical examination revealed only dependent petechiae. Theplatelets were 15,000, WBC 875, Hct 35 (after transfusion) andthe marrow biopsy was devoid of hematologic elements. Thepatient was given prednisone and fluoxymesterone. After one

week without response, a splenectomy was performed complicatedby postoperative pneumonitis. Hemostasis was assured by plateletinfusion therapy during surgery and postoperatively until his death.A total of 100 platelet concentrates, 20 platelet-rich plasma, and20 units of fresh whole blood was given. At no time was a hema-

tologic response to medical therapy or splenectomy noted. Theremainder of his life was characterized by recurrent sepsis.Comment. Although it was recognized that total aplasia of

the marrow has rarely been followed by a remission, splenectomyhas been performed to achieve this end. The procedure was com-

plicated by pneumonitis and was not followed by hematologicimprovement. It is of interest that 80 postoperative platelet ad-ministrations were not associated with a platelet antibody."0 Deathwas due to infection.

Case No. 14, D. H. This 31-year-old male was hospitalized fora severe autoimmune hemolytic anemia showing anti-c,C,e,Especificity, responsive to three months of 60 mg of prednisonedaily. No etiology for the hemolytic process was found and hewas discharged without medication with a hematocrit of 45. Hewas well until he experienced an exacerbation with jaundice,anemia, and hemoglobinuria. Prednisone, 60 mg a day, was

reinstituted with return of the Hct to 48 from 28. Again, an

etiology for the hemolytic anemia was not apparent. Splenectomywas performed and complicated by left lower lobe pneumonitis.Prednisone was gradually tapered and discontinued after threemonths. He has had normal hematocrit for two years.Comment. A severe autoimmune hemolytic anemia responded

to 60 mg prednisone daily for 3 months only to relapse 8 monthslater. Again, there was a response to the same dosage of predni-sone. After 5 months of treatment, splenectomy was performed.'The delay in operation was due to difficulty in cross-matching as

the patient was compatible only with -D- or Rh..,, cells. Be-cause of the severity of the hemolytic episodes, even though eachwas responsive to prednisone, splenectomy was considered advis-able because of the virtual impossibility of transfusing the patientand the hazards of long-term steroids.

Case No. 15, W. S. At the age of 25, an axillary node biopsywas interpreted as Hodgkin's disease. One thousand rads were

given to each axilla, the only sites of adenopathy. Eight yearslater, an appendectomy was performed with the remainder ofthe abdominal exploration judged normal. Chills, fever, and a

12-pound weight loss prompted admission 12 years after diagnosis.Physical examination revealed hepatosplenomegaly. The plateletcount was 35,000, WBC 1,300, and Hct 17. Splenectomy was

perfonned with operative platelet infusions. The postoperative

764 Ann. Surg. - Dec. 1973

COMPELLING SPLENECTOMY

course was complicated by a right lower lobe pneumonitis. Thehematologic response was a platelet count of 330,000, Hct 28,and WBC 7,000. Four months after surgery, he developed peri-orbital cellulitis and a nephrotic syndrome. At autopsy, Hodgkin'sdisease was found in the liver and lymph nodes, similar to theoperative histologic specimens of the spleen, lymph nodes and rib.Comment. The prolonged course of Hodgkin's disease in this

patient is remarkable in view of the radiotherapy given which,in view of present knowledge, would be deemed inadequate. Theprogressive and severe thrombocytopenia responded to splenec-tomy. Although the hematologic response was satisfactory, theunderlying disease was unaltered. The patient died of a severe

nephrotic syndrome prior to the time that chemotherapy couldbe instituted for Hodgkin's disease.

Results and Discussion

All but one of the patients were seriously threatenedby thrombocytopenia. Six patients were administeredplatelet components prior to surgery. In each case, theindication was severe skin, mucous membrane, urologic,or gastrointestinal bleeding. Once treatment was insti-tuted, platelet counts were maintained over 10,000 untilsurgery was performed. During surgery, the plateletcount was kept over 30,000. Two additional patients were

transfused only intraoperatively to insure the same hemo-static platelet level. The postoperative platelet therapyindication was the same as preoperatively. The total unitsof platelet components given appear in Table 1.During and after surgery, hemostasis was uneventful.

To stanch serious clinical bleeding and maintain a plate-let level over 10,000 a substantial blood bank commitmentwas needed. In all cases, an operative platelet level of30,000 insured adequate hemostasis. Platelet infusion sup-

port traditionally has been geared toward a successfulsurgical procedure. Although this approach often may besufficient, some patients postoperatively may tax bloodbank logistics. The requirements of two patients withchronic granulocytic leukemia, namely, 182 and 22 plate-let units, and 80 units for the patient with aplasticanemia, were predictable. However, the 190 and 156-unitreplacement in two patients with thrombocytopenic lupuserythematosus was unexpected. One of these patients re-

mains alive and well; whereas, the other died two monthsafter surgery. Thus, planning of platelet support shouldnot only include the preoperative and surgical manage-

ment but also a delayed endogenous platelet recovery

must be anticipated.The platelet response to splenectomy in the 14 patients

with thrombocytopenia was assessed 2 months aftersurgery (Table 2), at which time they were free of plate-let replacement. Over the succeeding 2 months, all plate-let counts albove 200,000-400,000 returned to normal withthe exception of one patient with lupus erythematosus(E.S.) who remained unchanged at 800,000. Except forthose who required intensive chemotherapy for underly-

TABLE 1. Total Platelet Support.(Donor Units)

Case Preop Operative Postop

#1 (J-S.) 32 7 182#2 (E.S.) 30 14 156#3 (B.T.) 36 8 190#6 (H.H.) 65 8 22#7 (M.H.) 6 2 0

#12 (M.B.) 0 6 0#13 (M.M.) 50 10 80#15 (W.S.) 0 2 0

ing disease, there was no further substantial change inplatelet levels.

Considering a normal platelet count to be in excess of200,000 mm3, 9 patients attained this level. Four patientsincreased to levels of 40,000 to 200,000 without recur-rence of spontaneous hemorrhage. Only the one patientwith marrow aplasia was unresponsive. Thus, 64% ofpatients reached or exceeded normal levels and another29M, although thrombocytopenic, were free of hemor-rhage. Of the partial responders, 2 suffered fromsmoldering granulocytic leukemia and one was in theaccelerated phase of chronic granulocytic leukemia. Theremaining patient was stage 4-B Hodgkin's disease whowas operated in the hope of improving tolerance tochemotherapy. From this small sampling, it would ap-pear that a gratifying, but incomplete response may beanticipated in patients verging on acute granulocyticleukemia. Thus, 93% were responsive to splenectomy per-formed for correction of a thrombocytopenic bleedingdiathesis by either improving or normalizing circulatingplatelet levels.

Discontinuance of prednisone is well advised to avoidboth acute and chronic toxicity. Thus, a further consid-eration of the efficacy of splenectomy is the relief of this

TABLE 2. Platelet Results.(X 103/mm3)

Case Presplenectomy Postsplenectomy Diagnosis#1 (J.S.) 2 40 CGL*#2 (E.S.) 4 800 SLEt#3 (B.T.) 20 250 SLE#4 (A.F.) 49 480 HDt#5 (D.N.) 3 850 SLE#6 (H.H.) 4 250 CGL#7 (M.H.) 8 400 CGL#8 (A.T.) 20 130 HD#9 (C.D.) 65 220 HD

#10 (W.M.) 53 920 HD#11 (G.G.) 42 165 SGL§#12 (M.B.) 13 60 SGL#13 (M.M.) 15 15 Aplasia#15 (W.S.) 35 330 HD* Chronic granulocytic leukemiat Systemic lupus erythematosust Hodgkin's disease§ Smoldering granulocytic leukemia

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Ann. Surg. * Dec. 1973

TABLE 3. Prednisone Therapy.

Case Daily (mg) Weeks Discontiinuied

#1 (J.S.) 100 1 Yes#2 (E.S.) 60 1

100 2 Yes#3 (B.T.) 100 4 No#5 (D.N.) 20 1 Yes#7 (M.H.) 20 12 Yes#9 (C.D.) 60 8 Yes#10(W.M.) 60 8

40 12 Yes#13 (M.M.) 20 1 No#14 (D.H.) 60 16 Yes

drug. The dosage and length of therapy preoperativelyare listed in Table 3.Of the 9 patients administered steroids, 7 were dis-

continued within 2 months without adverse hematologiceffect. The 2 failures were the patient with aplasia andthe patient with severe thrombocytopenia associatedwith systemic lupus erythematosus who died 2 monthsafter surgery. Six of 7 who were withdrawn from thistreatment maintained normal hematology, and one wascompensated with a platelet count of 40,000. This patientwas in the aggressive form of chronic granulocytic leu-kemia. Thus, 78% of those on prednisone were success-fully removed from this medication.The hematologic improvement and the relief from

prednisone treatment are important, but what of the im-pact of splenectomy on life? This group of 15 is divided

TABLE 4.

AliveSurvival

Case Disease Splenectomy (months)

#14 (D.H.) AIHA Apr 70 26#5 (D.N.) SLE Oct 69 32#7 (M.H.) CGL Oct 67 56#2 (E.S.) SLE Dec 67 54

# 1 (G.G.) SGL Sep 65 81

BenefitedFunctioning

LifeCase Disease Splenectomy Death (months)

#12 (M.B.) SGL Mar68 Sep 70 28#4 (A.F.) HD Apr 69 Nov 71 30#6 (H.H.) CGL Jtul 68 Jun 70 20#9 (C.D.) HD Jan 68 Jun 69 16

#10 (W.M.) HD Nov67 Feb 70 26

Not BenefitedTotal Life

Case Disease Splenectomy Death (months)

#13 (M.M.) Aplasia Feb 67 Apr 67 3#15 (W.S.) HD Nov67 Mar 68 5#8 (A.T.) HD Mar71 Jul 71 5#1 (J.S.) CGL Sep 67 Jan 68 5#3 (B.T.) SLE Dec 69 Feb 70 2

TABLE 5. Surgical Complications.

Case Disease Steroids Complications

#1 (J.S.) CGL Yes None#2 (E.S.) SLE Yes Pneumonia#3 (B.T.) SLE Yes Ileal ulcer & bleeding

Anastomotic leak andperitonitis

#4 (A.F.) HD No None#5 (D.N.) SLE Yes None#6 (H.H.) CGL No Pancreatitis

Wound hematomaStaph. wound infection

#7 (M.H.) CGL Yes Pneumonia#8 (A.T.) HD No Pneumonia and

Staph. septicemiaStaph. wound infection

#9 (C.D.) HD Yes None#10 (W.M.) HD Yes None#11 (G.G.) SGL No Pneumonia and wound

hematoma#12 (M.B.) SGL No Pneumonia#13 (M.M.) AA Yes Pneumonia#14 (D.H.) AIHA Yes Pneumonia#15 (W.S.) HD No Pneumonia

into 3 subgroups: Those who have remained well or whohad extended survival, although requiring therapy forbasic disease; those who experienced a productive lifeprior to eventual death; and the last subgroup who dieda few months after surgery. There are 5 patients in eachsubgrouping, as shown in Table 4.Three of the patients remain alive and well, with nor-

mal hematology and without medication as of May 1972.The patient with chronic granulocytic leukemia requiresoutpatient maintenance chemotherapy to normalize histotal white count. He remains fully employed. The in-dividual with smoldering granulocytic leukemia mani-fested acute leukemia 79 months post-splenectomy and isnow being administered prednisone, vincristine sulfate,and 6-mercaptopurine.The 5 who benefited from splenectomy left the hos-

pital to become economically productive. They led anormal life until the end stages of their diseases. Func-tioning life was determined as the months followingsplenectomy in which their life was not compromised byintensive chemotherapy or hospitalization. The mean pro-ductive survival was 2 years.The final one-third who did not benefit died of the

basic disease with the exception of one late postopera-tive death. Of the remaining, 2 had Hodgkin's diseasestage 4-B, one was aplastic, and the other suffered a.blastic crisis of chronic granulocytic leukemia.

Considering that benefit from splenectomy may be an-ticipated in the medically compromised patient, thensurgical complications must be analyzed. In such a poorhost, the potential gain must be balanced against themorbidity and mortality. The surgical complications andother data appear in Table 5.

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Vol. 178 * No. 6 COMPELLING SPLENECTOMY 767

There was no mortality within 30 days following sur-gery. One patient died 2 months later of postoperativecomplications after her third surgical procedure. She de-veloped ileal edema, ulceration and bleeding one monthafter splenectomy. The terminal 3 feet of ileum were re-sected and primary anastomosis performed. She subse-quently died from anastomotic leakage, peritonitis, andsepticemia. It is suggested that this complication in apatient on high prednisone dosage might be better man-aged by ileostomy and colocutaneous fistula rather thanby resection and anastomosis.

In 10 of the 15 patients (67%), there were 15 compli-cations. One patient suffered 2 complications, and 2 pa-tients each experienced three. Eight of the 15 (53%o)postoperative problems were pneumonia. Such a highrate demands meticulous attention to postoperative pul-monary preventive measures.Of those 9 patients taking steroids, 5 experienced com-

plications. Of the 6 not taking steroids, 5 had complica-tions. This reversal of anticipated results may be partiallyexplained by underlying malignancy. Three of the pa-tients not taking steroids had leukemia and three hadHodgkin's disease.Of 10 patients in whom left subcostal incisions were

made, 3 had wound complications. Similarly, of 3 patientswith midline incisions, one experienced wound complica-tions. None occurred in the 2 patients having paramedianincisions. Retention sutures were employed in 5 patients,one of whom suffered wound complications; whereas, 3occurred in the 10 patients without retention sutures.These results permit little to be said regarding the pre-ferred incision or the use of retention sutures.There was no postoperative mortality in the 15 patients

subjected to splenectomy. The morbidity rate was high,namely 67%, composed predominantly of pneumonia. Ef-forts directed toward intensive postoperative pulmonarytoilet appear mandatory. In this small series, the type ofsurgical incision or the use of retention sutures does notseem to influence the wound complication rate. Lastly,postoperative problems were related more toward thebasic disease than to the preoperative use of steroids.

SummaryThe indication for splenectomy was considered urgent

in 15 patients with severe cytopenia. Fourteen werethreatened by thrombocytopenia and one by recurrenthemolytic anemia. This group of patients was further dis-tinguished by hematologic malignancy or autoimmunedisorder. Almost all had received some combination ofradiotherapy, steroids, or chemotherapy. Life-endanger-ing cytopenia, serious basic disease, and previous therapywith immunosuppressive agents characterize these pa-tients as medically compromised.There was no immediate operative mortality, although

one patient died 2 months after splenectomy. The mor-bidity was significant, namely 67%, with pneumonia beingthe leading postoperative problem. In 67% of patients, thecytopenia corrected to normal and all but one patient ex-perienced significant improvement. Seven of 9 patientswere successfully discontinued from prednisone whilemaintaining post-splenectomy gains. The 15 patients wereequally divided into 3 subgroups regarding those whoremain alive, those who experienced significant improve-ment in functioning life, and those without benefit. Thisexperience may assist the physician who must balance therisk versus the potential gain when the indication forsplenectomy appears compelling, yet the patient's condi-tion is medically compromised.

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768Anni. Surg. *Dec. 1973

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22. Schultz, J. C., Denny, W. F. and Ross, S. W.: Splenectomyin Leukemia and Lymphoma: Report of 24 Cases. Amer-J. Med. Sci., 247:30, 1964.

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