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Splenectomy for cytopenias associated with systemic lupus erythematosus
Splenectomy for Cytopenias Associated With Systemic Lupus Erythematosus William
W. Coon, M D , Ann Arbor, Michigan
The utilization of splenectomy for the managemen t of cytopenias, particularly thrombocytopenia, associated with systemic lupus erythematosus has become highly controversial. Although several groups of investigators have reported sustained remission of thrombocytopenia after splenectomy, others have recently claimed a high rate of initial failure or early relapse of autoimmune cytopenia after operation [1-4]. One of the reports favoring splenectomy has been criticized because criteria used for the diagnosis of systemic lupus erythematosus were not those of the American Rheumatism Association [5,6]. Our experience with this rare Complication of systemic lupus erythematosus, diagnosed according to the aforementioned criteria, has been as large or larger than that of other series. This group of patients is reported to demonstrate that splenectomy may still be of value in carefully selected patients with systemic lupus erythematosus and autoimmune cytopenias, although results are not equivalent to those achieved in patients with conventional idiopathic thrombocytopenic purpura. Methods
All patients who underwent splenectomy for the preoperative diagnosis of systemic lupus erythemat0sus and autoimmune cytopenia at our hospital during a 25 year period were included. In each patient, the diagnosis of systemic lupus erythemat0sus was confirmed by our rheumatologists using the criteria of the American Rheumatism Association, which include the presence of any 4 of the following 11 criteria, either serially or simultaneously: malar rash;discoid rash; photosensitivity; oral ulcers; From the Department of Surgery, The University of Michigan Medical Center, Ann Arbor, Michigan. Requests for reprints should be addressed to William W. Coon, MD, Department of Surgery, The University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109.
Volume 155, March 1988
nonerosive arthritis; serositis; renal disorder, such as proteinuria and cellular casts; neurolQgic disorder; hematologic disorder, such as hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia; and immunologic disorder, such as positive lupus erythematosus preparation, anti-DNA, anti:Sin, or false-positive result on serologic test for syphilis; and an abnormality of antinuclear antibody [6]. In several patients operated on before 1971, the established Criteria were confirmed retrospectively. Two patients in our recent serie s of 216 splenectomies for idiopathi c thrombocytopenia purpura who had the diagnosis Of systemic lupus erythematosus made months to years after splenectomy were not included in this analysis [71. Results Of the 20 patients studied, 7 had more than one clinically significant cytopenia. There were !5 women and 5 men with ages ranging between 20 and 62 years at the time of operation. All but four patient s had an established diagnosis of systemic lupus erythcmatosus for more than 1 year before operation and five had active disease for more than 10 years. Table I lists the cytologic response to sp!enectomy. The hematocrit value and white blood cell count are listed only for those patients with significantly depressed values (hematocrit value 30 percent or less or white blood cell count less than 3,000/ mma). In 18 patients, thrombocytopen!a was the principal indication for splenectomy. One of these patients (Patient 18) had major pancyt0penia and all cellular elements increased after splenectomy. Patient 8 had fluctuating platelet counts for 4 years while being treated with 15 to 40 mg of prednisone by the referring physician. Relapse of thrombocytopenia had repeatedly occurred when an attempt was made to decrease the dosage of prednisone. In the two remaining patients (Patients I and 7), autoim391
Coon
TABLE I
Patient
Cytologic Response to Splenectomy Age (yr) & Sex
1 2
22, F 25, F
160 28
3
44, F
1
4 5 6 7
54, 44, 21, 54,
F F F F
3 10 10 350
8
62, F
60
. . . . . .
9 10 11 12 13 14 15
27, 32, 57, 29, 58, 26, 37,
M F M F F M F
2 10 5 1 8 29 18
28 ... . . . . . . . . . . . . ... '28 ... . . . . . . . . . . . .
16
36, M
15
. . . . . .
17 18 19 20
39, 56, 35, 20,
20 44 3 43
"26-. . . . . . . . . . .
F M F F
Medication
Before Operation P H WBC (1,000/mm 3) (%) (cells/mm 3) 28 20
2,000 ...
. . . . . . .. 30'
... ...
"20
2,400 :"
Preoperative (mg/d)
Postoperative (mg/d)
None MethYl prednisolone, 80 cyclophosphamide, 125 Prednisone, 80, danazol, 600 Prednisone, 100 Prednisone, 20 Prednisone, 60 9Prednisone, 30, cyclophosphamide, 100 Prednisone, 15-40, azathioprine, 50 Prednisone, 60 Prednisone, 60 Prednis0ne, 60 Prednisone, 60-100 Prednisone, 100 Prednisone, 80 Prednisone, 40 Cyclophosphamide, 50 Hydrocortisone, 240
Prednisone, 25-10 Prednisone, 30 Cyclophosphamide, 50 Prednisone~ 10-60
Prednisone, 40 None Prednisone, 60 Prednisone, 15-60, frentizole, 225
mS00 :
None Methyl prednisolone, !0 Steroid taper None Prednisone, 1Q Hydrocortisone, 320 None Prednisone, 5 Prednisone, 60-20 None Prednisone, 25 (taper) Prednisone, 9 Prednisone, 60-none at last follow-up Prednisone, 25 None None Prednisone, 25-12.5
* Death. H = hematocrit value; P = platelet count; WBC = white blood cell count.
mune hemolytic anemia was the chief reason for operation. Both had mild leukopenia. Although seven patients were still receiving steroids at the time of last follow-up, the steroids were being utilized in five patients to treat other manifestations of active systemic lupus erythematosus. Thirteen of the 18 patients operated on for thrombocytopenia had a normal platelet count (150,000 cells/mm ~ or more) at last follow-up. Of the five remaining patients, one had a stable platelet coting of 80,000 cells/mm 3. Three of the other four patients died, two from renal complications of systemic lupus erythematosus and one from carcinoma of the lung. One patient (Patient 3) had bleeding problems during the postoperative observation period. Another patient (Patient 12) had periodic relapses of thromb0cytopenia requiring short courses of steroid treatment, but at last follow-up She had a normal platelet count while receiving 10w doses of prednisone as required for the management of joint symptoms. Sixteen of the 18 thrombocytopenic patients were given high doses of steroids with or without other adjunctive immunosuppressive agents before operation. Eight had a platelet response (100,000 ceils/ mm 3 or more), and a normal platelet count after
392
splenectomy was achieved in seven of these patients. Of the remaining eight patients who had a lesser or no response to these immunosuppressive agents, four had normal postsplenectomy platelet values and in four the values were below normal. Seven patients had clinically significant autoimmune hemolytic anemia: five patients had a sustained increase in the hematocrit value of 30 percent or greater after operation, and one patient had a sustained increase of greater than 20 percent. A similar satisfactory response was observed in the three patients with leukopenia. Subphrenic abscess, renal, and respiratory insufficiency developed in one patient (Patient 9) with severe systemic lupus erythematosus including lupus cerebritis. This patient died 4 weeks after operation. No other postoperative complications were encountered. Blood transfusions during operation were required in only three instances. Eight patients, including the more recently seen patients, those who died, and those lost to follow-up, were followed for less than 1 year. Comments
The present study was confined to patients with preexisting systemic lupus erythematosus and severe cytopenias since it isthis circumstance in which
The American Journal of Surgery
Splenectomy in Systemic Lupus Erythematosus
P (1,000/mm 3)
H (%)
317 330
43 33
14
...
480 27 8OO 450
"32
525
...
At Last Follow-Up WBC (cells/mm 3) 6,800
Mo 141 12 6*
"42
6:000
6 22* 1 38
345 580 358
"34 ... ...
1 81 26* 27 10 1 184
210
...
141
37 530 380 460
'37 ... ...
33
27
400
...
80
...
481
s:600 ... ...
32
4 62 20
a surgeon consulted regarding splenectomy is required to make an informed decision. Our results in this form of autoimmune thrombocytopenia were similar to our recent 20 year experience with 216 patients with idiopathic thrombocytopenic purpura in which diagnosis depends on the elimination of any demonstrable underlying cause for a diminution in platelet number [7]. That results should be s o m e w h a t comparable is not surprising in view of the fact that both conditions are autoimmune in nature and brought about by the formation of antiplatelet antibodies. In our experience with patients with idiopathic thrombocytopenic purpura, 72 percent achieved an immediate platelet response (150,000 cells/mm 3 or more) without subsequent relapse. The results in thrombocytopenic patients with systemic lupus erythematosus was a 67 percent immediate and sustained response during the follow-up period. This comparison must be tempered by the fact that seven of these 12 patients in whom treatment was successful were followed for less than 1 year. Relapse may occur in some of these patients in the future. Late relapse may occur more frequently in patients with systemic lupus erythematosus. Of our 60 patients with idiopathic thrombocytopenic purpura who were considered to have a suboptimal response to splenectomy, only 3 had a first relapse more than 1 year after splenectomy. All
Volume 155, March 1988
of the other patients either did not achieve a platelet count of 150,000 cells/ram 3 initially or had a subsequent decrease in platelet count during the first 12 months of postoperative follow-up [7]. In patients with systemic lupus erythematosus, the disease may wax and wane. Those patients with more severe manifestations, such as renal insufficiency and lupus cerebritis, have a greater chance of less than an optimal platelet response after splenectorny. If the primary disease worsens during prolonged follow-up, the frequency of late recurrence of thrombocytopenia may be higher than in those patients with idiopathic thrombocytopenic purpura. In addition, continued treatment after operation with immunosuppressive drugs may influence the hematologic picture either favorably or unfavorably. Continued treatment with prednisone or a related adrenal corticosteroid may contribute to the sustained elevation of platelet count or hematocrit value. Cyclophosphamide or azathioprine may depress the bone marrow and decrease blood cell counts or it may decrease the severity of the primary disease and thus lessen the hazard of cytologic relapse. No criteria other than severity of underlying systemic lupus erythematosus were found that might predict cytologic response after splenectomy. Although just as in patients with idiopathic thromhocytopenic purpura, a preoperative increase in platelets after administration of high-dose steroid therapy appears to be associated with a somewhat greater likelihood of a satisfactory result from splenectomy, many patients who do not have a response to steroids do have a normal platelet count after removal of the spleen [7]. Since the hematologic response to operation is unpredictable in patients with systemic lupus erythematosus, other therapeutic measures should be considered before recommending splenectomy, including high-dose steroid therapy and perhaps danazol, vincristine, or plasmapheresis. However, if these measures fail or if more than 15 mg of prednisone per day is required for a prolonged period, removal of the spleen appears to be justified on the basis of our observations of favorable cytologic response in some patients. Summary Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm 3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count
393
Coon
increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment. References 1. Breckenridge RT, Moore RD, Ratnoff OD. A study of thrombocytopenia: new histologic criteria for the differentiation of idiopathic thrombocytopenia and thrombocytopenia associated with disseminated lupus erythematosus. Blood 1967; 30: 39-51. 2. Homan WP, Dineen P. The role of splenectomy in the treat-
394
3. 4.
5. 6. 7.
ment of thrombocytopenic purpura due to systemic lupus erythematosus. Ann Surg 1978; 187: 52-6. Rivero SJ, Alger M, Alarion-Segovia D. Splenectomy for hematocytopenia in systemic lupus erythematosus: a controlled appraisal. Arch intern Med 1979; 139: 773-6. Hall S, McCormick JL, Greipp PR, Michet CJ Jr., McKenna CH. Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus. Ann Intern Med 1985; 102: 325-8. Cohen AS, Reynolds WE, Franklin EC, et al. Preliminary criteria for the classification of systemic lupus erythematosus. Bull Rheum Dis 1981; 21: 643-8. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7. Coon WW. Splenectomy for idiopathic thrombocytopenic purpura. Surg Gynecol Obstet 1987; 164: 225-9.
The American Journal of Surgery
W. Coon, M D , Ann Arbor, Michigan
The utilization of splenectomy for the managemen t of cytopenias, particularly thrombocytopenia, associated with systemic lupus erythematosus has become highly controversial. Although several groups of investigators have reported sustained remission of thrombocytopenia after splenectomy, others have recently claimed a high rate of initial failure or early relapse of autoimmune cytopenia after operation [1-4]. One of the reports favoring splenectomy has been criticized because criteria used for the diagnosis of systemic lupus erythematosus were not those of the American Rheumatism Association [5,6]. Our experience with this rare Complication of systemic lupus erythematosus, diagnosed according to the aforementioned criteria, has been as large or larger than that of other series. This group of patients is reported to demonstrate that splenectomy may still be of value in carefully selected patients with systemic lupus erythematosus and autoimmune cytopenias, although results are not equivalent to those achieved in patients with conventional idiopathic thrombocytopenic purpura. Methods
All patients who underwent splenectomy for the preoperative diagnosis of systemic lupus erythemat0sus and autoimmune cytopenia at our hospital during a 25 year period were included. In each patient, the diagnosis of systemic lupus erythemat0sus was confirmed by our rheumatologists using the criteria of the American Rheumatism Association, which include the presence of any 4 of the following 11 criteria, either serially or simultaneously: malar rash;discoid rash; photosensitivity; oral ulcers; From the Department of Surgery, The University of Michigan Medical Center, Ann Arbor, Michigan. Requests for reprints should be addressed to William W. Coon, MD, Department of Surgery, The University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109.
Volume 155, March 1988
nonerosive arthritis; serositis; renal disorder, such as proteinuria and cellular casts; neurolQgic disorder; hematologic disorder, such as hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia; and immunologic disorder, such as positive lupus erythematosus preparation, anti-DNA, anti:Sin, or false-positive result on serologic test for syphilis; and an abnormality of antinuclear antibody [6]. In several patients operated on before 1971, the established Criteria were confirmed retrospectively. Two patients in our recent serie s of 216 splenectomies for idiopathi c thrombocytopenia purpura who had the diagnosis Of systemic lupus erythematosus made months to years after splenectomy were not included in this analysis [71. Results Of the 20 patients studied, 7 had more than one clinically significant cytopenia. There were !5 women and 5 men with ages ranging between 20 and 62 years at the time of operation. All but four patient s had an established diagnosis of systemic lupus erythcmatosus for more than 1 year before operation and five had active disease for more than 10 years. Table I lists the cytologic response to sp!enectomy. The hematocrit value and white blood cell count are listed only for those patients with significantly depressed values (hematocrit value 30 percent or less or white blood cell count less than 3,000/ mma). In 18 patients, thrombocytopen!a was the principal indication for splenectomy. One of these patients (Patient 18) had major pancyt0penia and all cellular elements increased after splenectomy. Patient 8 had fluctuating platelet counts for 4 years while being treated with 15 to 40 mg of prednisone by the referring physician. Relapse of thrombocytopenia had repeatedly occurred when an attempt was made to decrease the dosage of prednisone. In the two remaining patients (Patients I and 7), autoim391
Coon
TABLE I
Patient
Cytologic Response to Splenectomy Age (yr) & Sex
1 2
22, F 25, F
160 28
3
44, F
1
4 5 6 7
54, 44, 21, 54,
F F F F
3 10 10 350
8
62, F
60
. . . . . .
9 10 11 12 13 14 15
27, 32, 57, 29, 58, 26, 37,
M F M F F M F
2 10 5 1 8 29 18
28 ... . . . . . . . . . . . . ... '28 ... . . . . . . . . . . . .
16
36, M
15
. . . . . .
17 18 19 20
39, 56, 35, 20,
20 44 3 43
"26-. . . . . . . . . . .
F M F F
Medication
Before Operation P H WBC (1,000/mm 3) (%) (cells/mm 3) 28 20
2,000 ...
. . . . . . .. 30'
... ...
"20
2,400 :"
Preoperative (mg/d)
Postoperative (mg/d)
None MethYl prednisolone, 80 cyclophosphamide, 125 Prednisone, 80, danazol, 600 Prednisone, 100 Prednisone, 20 Prednisone, 60 9Prednisone, 30, cyclophosphamide, 100 Prednisone, 15-40, azathioprine, 50 Prednisone, 60 Prednisone, 60 Prednis0ne, 60 Prednisone, 60-100 Prednisone, 100 Prednisone, 80 Prednisone, 40 Cyclophosphamide, 50 Hydrocortisone, 240
Prednisone, 25-10 Prednisone, 30 Cyclophosphamide, 50 Prednisone~ 10-60
Prednisone, 40 None Prednisone, 60 Prednisone, 15-60, frentizole, 225
mS00 :
None Methyl prednisolone, !0 Steroid taper None Prednisone, 1Q Hydrocortisone, 320 None Prednisone, 5 Prednisone, 60-20 None Prednisone, 25 (taper) Prednisone, 9 Prednisone, 60-none at last follow-up Prednisone, 25 None None Prednisone, 25-12.5
* Death. H = hematocrit value; P = platelet count; WBC = white blood cell count.
mune hemolytic anemia was the chief reason for operation. Both had mild leukopenia. Although seven patients were still receiving steroids at the time of last follow-up, the steroids were being utilized in five patients to treat other manifestations of active systemic lupus erythematosus. Thirteen of the 18 patients operated on for thrombocytopenia had a normal platelet count (150,000 cells/mm ~ or more) at last follow-up. Of the five remaining patients, one had a stable platelet coting of 80,000 cells/mm 3. Three of the other four patients died, two from renal complications of systemic lupus erythematosus and one from carcinoma of the lung. One patient (Patient 3) had bleeding problems during the postoperative observation period. Another patient (Patient 12) had periodic relapses of thromb0cytopenia requiring short courses of steroid treatment, but at last follow-up She had a normal platelet count while receiving 10w doses of prednisone as required for the management of joint symptoms. Sixteen of the 18 thrombocytopenic patients were given high doses of steroids with or without other adjunctive immunosuppressive agents before operation. Eight had a platelet response (100,000 ceils/ mm 3 or more), and a normal platelet count after
392
splenectomy was achieved in seven of these patients. Of the remaining eight patients who had a lesser or no response to these immunosuppressive agents, four had normal postsplenectomy platelet values and in four the values were below normal. Seven patients had clinically significant autoimmune hemolytic anemia: five patients had a sustained increase in the hematocrit value of 30 percent or greater after operation, and one patient had a sustained increase of greater than 20 percent. A similar satisfactory response was observed in the three patients with leukopenia. Subphrenic abscess, renal, and respiratory insufficiency developed in one patient (Patient 9) with severe systemic lupus erythematosus including lupus cerebritis. This patient died 4 weeks after operation. No other postoperative complications were encountered. Blood transfusions during operation were required in only three instances. Eight patients, including the more recently seen patients, those who died, and those lost to follow-up, were followed for less than 1 year. Comments
The present study was confined to patients with preexisting systemic lupus erythematosus and severe cytopenias since it isthis circumstance in which
The American Journal of Surgery
Splenectomy in Systemic Lupus Erythematosus
P (1,000/mm 3)
H (%)
317 330
43 33
14
...
480 27 8OO 450
"32
525
...
At Last Follow-Up WBC (cells/mm 3) 6,800
Mo 141 12 6*
"42
6:000
6 22* 1 38
345 580 358
"34 ... ...
1 81 26* 27 10 1 184
210
...
141
37 530 380 460
'37 ... ...
33
27
400
...
80
...
481
s:600 ... ...
32
4 62 20
a surgeon consulted regarding splenectomy is required to make an informed decision. Our results in this form of autoimmune thrombocytopenia were similar to our recent 20 year experience with 216 patients with idiopathic thrombocytopenic purpura in which diagnosis depends on the elimination of any demonstrable underlying cause for a diminution in platelet number [7]. That results should be s o m e w h a t comparable is not surprising in view of the fact that both conditions are autoimmune in nature and brought about by the formation of antiplatelet antibodies. In our experience with patients with idiopathic thrombocytopenic purpura, 72 percent achieved an immediate platelet response (150,000 cells/mm 3 or more) without subsequent relapse. The results in thrombocytopenic patients with systemic lupus erythematosus was a 67 percent immediate and sustained response during the follow-up period. This comparison must be tempered by the fact that seven of these 12 patients in whom treatment was successful were followed for less than 1 year. Relapse may occur in some of these patients in the future. Late relapse may occur more frequently in patients with systemic lupus erythematosus. Of our 60 patients with idiopathic thrombocytopenic purpura who were considered to have a suboptimal response to splenectomy, only 3 had a first relapse more than 1 year after splenectomy. All
Volume 155, March 1988
of the other patients either did not achieve a platelet count of 150,000 cells/ram 3 initially or had a subsequent decrease in platelet count during the first 12 months of postoperative follow-up [7]. In patients with systemic lupus erythematosus, the disease may wax and wane. Those patients with more severe manifestations, such as renal insufficiency and lupus cerebritis, have a greater chance of less than an optimal platelet response after splenectorny. If the primary disease worsens during prolonged follow-up, the frequency of late recurrence of thrombocytopenia may be higher than in those patients with idiopathic thrombocytopenic purpura. In addition, continued treatment after operation with immunosuppressive drugs may influence the hematologic picture either favorably or unfavorably. Continued treatment with prednisone or a related adrenal corticosteroid may contribute to the sustained elevation of platelet count or hematocrit value. Cyclophosphamide or azathioprine may depress the bone marrow and decrease blood cell counts or it may decrease the severity of the primary disease and thus lessen the hazard of cytologic relapse. No criteria other than severity of underlying systemic lupus erythematosus were found that might predict cytologic response after splenectomy. Although just as in patients with idiopathic thromhocytopenic purpura, a preoperative increase in platelets after administration of high-dose steroid therapy appears to be associated with a somewhat greater likelihood of a satisfactory result from splenectomy, many patients who do not have a response to steroids do have a normal platelet count after removal of the spleen [7]. Since the hematologic response to operation is unpredictable in patients with systemic lupus erythematosus, other therapeutic measures should be considered before recommending splenectomy, including high-dose steroid therapy and perhaps danazol, vincristine, or plasmapheresis. However, if these measures fail or if more than 15 mg of prednisone per day is required for a prolonged period, removal of the spleen appears to be justified on the basis of our observations of favorable cytologic response in some patients. Summary Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm 3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count
393
Coon
increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment. References 1. Breckenridge RT, Moore RD, Ratnoff OD. A study of thrombocytopenia: new histologic criteria for the differentiation of idiopathic thrombocytopenia and thrombocytopenia associated with disseminated lupus erythematosus. Blood 1967; 30: 39-51. 2. Homan WP, Dineen P. The role of splenectomy in the treat-
394
3. 4.
5. 6. 7.
ment of thrombocytopenic purpura due to systemic lupus erythematosus. Ann Surg 1978; 187: 52-6. Rivero SJ, Alger M, Alarion-Segovia D. Splenectomy for hematocytopenia in systemic lupus erythematosus: a controlled appraisal. Arch intern Med 1979; 139: 773-6. Hall S, McCormick JL, Greipp PR, Michet CJ Jr., McKenna CH. Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus. Ann Intern Med 1985; 102: 325-8. Cohen AS, Reynolds WE, Franklin EC, et al. Preliminary criteria for the classification of systemic lupus erythematosus. Bull Rheum Dis 1981; 21: 643-8. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7. Coon WW. Splenectomy for idiopathic thrombocytopenic purpura. Surg Gynecol Obstet 1987; 164: 225-9.
The American Journal of Surgery