Original Article
High-Dose Intravenous Immune Globulin and the Response to Splenectomy in Patients with Idiopathic Thrombocytopenic Purpura
N Engl J Med 1997; 336:1494-1498May 22, 1997
- Abstract
Background
High-dose intravenous immune globulin produces a temporary rise in the platelet count in patients with idiopathic thrombocytopenic purpura. Splenectomy may also be effective, but it is not possible to predict which patients will have a good response. We hypothesized that the response to intravenous immune globulin predicts the response to splenectomy.
Methods
We studied retrospectively 30 patients with idiopathic thrombocytopenic purpura who had first been treated with immune globulin and then undergone splenectomy. The responses to the two treatments were classified on the basis of the platelet count as poor (<50,000 per cubic millimeter), good (50,000 to 150,000 per cubic millimeter), or excellent (>150,000 per cubic millimeter).
Results
All nine patients who had poor responses to intravenous immune globulin also had poor responses to splenectomy at one year. Of the 21 patients with good or excellent responses to intravenous immune globulin, 19 had good or excellent responses to splenectomy.
Conclusions
Patients with idiopathic thrombocytopenic purpura who have good or excellent responses to intravenous immune globulin are likely to have good or excellent responses to splenectomy, whereas patients who have poor responses to intravenous immune globulin are unlikely to have good or excellent responses to splenectomy.
Media in This Article
Figure 1
Response to Intravenous Immune Globulin in Relation to the Response to Splenectomy at One Year in 30 Patients with Idiopathic Thrombocytopenic Purpura.Figure 2
Platelet Counts in Two Patients with Idiopathic Thrombocytopenic Purpura Treated with Intravenous Immune Globulin and Splenectomy.Article Activity
- Article
Idiopathic thrombocytopenic purpura is a disorder in which antiplatelet autoantibodies cause the destruction of platelets, resulting in thrombocytopenia. In children, idiopathic thrombocytopenic purpura tends to be acute and short-lived, with only supportive management required. In most adults, however, the disorder is chronic and often requires medical therapy or splenectomy.1-7 Splenectomy results in clinical improvement in about two thirds of patients with chronic idiopathic thrombocytopenic purpura, but it is not possible to predict reliably which patients will benefit from the procedure.3 A number of variables have been evaluated as possible predictive factors, including the response to corticosteroids,8,9 age, sex, and the pattern of clearance of radiolabeled platelets by the liver and spleen, but none have accurately predicted the result of splenectomy.10-13
Treatment with high-dose intravenous immune globulin causes a transient rise in the platelet count in many patients with idiopathic thrombocytopenic purpura.2,3,14 This effect may be due, at least in part, to blockade of the Fc receptors of macrophages, particularly in the spleen.14-18 The blockade of Fc receptors by intravenous immune globulin prevents phagocytosis of antibody-coated platelets by splenic macrophages. In view of this mechanism, we hypothesized that patients who have good responses to immune globulin might also have good responses to splenectomy. In this report, we describe a series of 30 patients with idiopathic thrombocytopenic purpura who were treated with high-dose intravenous immune globulin and subsequently underwent splenectomy. We found that the response to intravenous immune globulin was a sensitive and specific predictor of the response to splenectomy.
Methods
Patients
All the patients in this study had chronic idiopathic thrombocytopenic purpura, which was defined as thrombocytopenia (platelet count, <150,000 per cubic millimeter) that had persisted for a minimum of three months without other clinical or laboratory findings that could explain it. All the patients were treated with 2 g of intravenous immune globulin per kilogram of body weight (Miles Canada, Etobicoke, Ont.), administered in a dose of 1 g per kilogram over a period of six to eight hours, with the same dose repeated the next day. All the patients subsequently underwent either left subcostal open splenectomy or left lateral laparoscopic splenectomy.
Patients were excluded from the study if they had a positive serologic test for the human immunodeficiency virus (HIV) or risk factors for HIV infection, in the absence of test results; if they had systemic lupus erythematosus; or if they had not been treated with intravenous immune globulin before undergoing splenectomy.
Study Design
The study was a retrospective analysis of consecutive patients treated at McMaster University Medical Centre between 1984 and 1995 who met the eligibility criteria. Eligible patients were identified by searching the computerized patient-information data base at the center and by reviewing the records of one of us.
Response to Treatment
The responses to high-dose intravenous immune globulin and splenectomy were defined in the same way. An excellent response was defined as a platelet count that rose to a normal level (>150,000 per cubic millimeter) after treatment. A good response was defined as a platelet count of 50,000 to 150,000 per cubic millimeter. A poor response was defined as a platelet count below 50,000 per cubic millimeter after treatment. We used a platelet count of 50,000 per cubic millimeter as the threshold for a good response because, in our experience, most patients with platelet counts at or above this level do not have bleeding or require therapy. The response to intravenous immune globulin was classified according to the response to the initial course. The platelet count was measured three to seven days after treatment. All patients were followed for a minimum of 12 months after surgery. Patients whose platelet counts fell below 50,000 per cubic millimeter and who required medical therapy for idiopathic thrombocytopenic purpura at any time after surgery were considered to have poor responses. Patients considered to have good or excellent responses to splenectomy received no additional medical therapy during follow-up.
Statistical Analysis
We calculated the specificity, sensitivity, and positive and negative predictive values of a response to intravenous immune globulin as a predictor of the response to splenectomy.
Results
Patients
A search of the computer data base identified 82 consecutive patients who had received a diagnosis of idiopathic thrombocytopenic purpura and had undergone splenectomy at McMaster University Medical Centre between 1984 and 1995. Thirty-four patients were excluded because they did not receive intravenous immune globulin, 15 were excluded because another cause of thrombocytopenia was identified, and 3 had incomplete follow-up data.
Of the 30 eligible patients, 18 were female and 12 were male. The age range was 2 to 80 years at presentation. Nine patients were under the age of 15 years, and three were less than 6 (5, 4, and 2 years of age); the rest were adults.
Clinical manifestations of idiopathic thrombocytopenic purpura included purpura (in 80 percent of the patients), petechiae (in 63 percent), epistaxis (in 43 percent), gingival bleeding (in 10 percent), menorrhagia (in 7 percent), and gastrointestinal bleeding (in 6 percent). Twenty-seven of the patients had had thrombocytopenia for more than three months before undergoing splenectomy, and three (two adults and one child) had had thrombocytopenia for only three months when the surgery was performed. These three patients had poor responses to splenectomy, and chronic idiopathic thrombocytopenic purpura was subsequently diagnosed in all three.
Bone marrow examinations were performed in 14 of the 30 patients, and in all 14, the results were consistent with a diagnosis of idiopathic thrombocytopenic purpura. Antinuclear-antibody tests were performed in 20 patients (15 adults and 5 children), and all 20 had negative results. During follow-up, none of the patients had clinical or laboratory evidence of HIV infection or systemic lupus erythematosus.
Before undergoing splenectomy, all but two patients had received corticosteroid treatment, with variable responses. In addition, six patients had received intravenous anti-RhD immune globulin, two had been given danazol, two had undergone splenic irradiation, and one had received cyclophosphamide.
Twenty-seven patients underwent open splenectomy, and three underwent laparoscopic splenectomy. The pathological findings in spleen specimens from all 30 patients were consistent with the diagnosis of idiopathic thrombocytopenic purpura.
Response to Treatment
Nine patients had poor responses to high-dose intravenous immune globulin, 12 had good responses, and 9 had excellent responses. All patients had relapses within one month after receiving the first course of intravenous immune globulin. The responses to additional courses of intravenous immune globulin were less pronounced and lasted for shorter periods than the initial responses.
Table 1Table 1
Characteristics of 30 Patients with Idiopathic Thrombocytopenic Purpura, According to the Response to Splenectomy. shows the characteristics of the patients according to their responses to splenectomy. The responses were poor in 11 patients, good in 2, and excellent in 17. Of the 11 patients whose responses were classified as poor, 3 had no measurable response, 5 had relapses within 6 months after undergoing splenectomy, and 3 had relapses 6 to 14 months after surgery. All 11 patients received subsequent medical treatment. An accessory spleen was suspected in three of these patients; in two an accessory spleen was removed, but in the third no accessory spleen was found at laparotomy. Removal of the spleen was not beneficial in any of the patients. Subsequent investigations revealed bone marrow hypoplasia (diagnosed 16 months after splenectomy) in one of these three patients and an abnormal bone marrow karyotype — XY del(13)(q32) in 4 of 20 cells — of unknown relevance in another patient. No evidence of systemic lupus erythematosus or another condition that could explain the persistent thrombocytopenia was found in the patients with poor responses to splenectomy.None of the 19 patients with good or excellent responses required further treatment. Follow-up of these 19 patients ranged from 12 months (in 13 patients) to 8 years.
Relation between Responses to Intravenous Immune Globulin and Splenectomy
There was a close relation between the response to high-dose intravenous immune globulin and the outcome of splenectomy (Figure 1Figure 1
Response to Intravenous Immune Globulin in Relation to the Response to Splenectomy at One Year in 30 Patients with Idiopathic Thrombocytopenic Purpura.). Figure 2AFigure 2Platelet Counts in Two Patients with Idiopathic Thrombocytopenic Purpura Treated with Intravenous Immune Globulin and Splenectomy. and Figure 2Bshows the clinical courses in two representative patients: one with excellent responses to both intravenous immune globulin and splenectomy, and one with poor responses to both treatments. All nine patients who had poor responses to high-dose intravenous immune globulin also had poor responses to splenectomy. In contrast, of the 21 patients who had good or excellent responses to intravenous immune globulin, 19 had good or excellent responses to splenectomy. Two patients had poor responses to splenectomy despite a good or excellent response to intravenous immune globulin.The sensitivity of the response to intravenous immune globulin as a predictor of the response to splenectomy was 100 percent, and the specificity was 81.8 percent, with a positive predictive value of 90.5 percent and a negative predictive value of 100 percent.
Discussion
Idiopathic thrombocytopenic purpura affects both children and adults. The childhood form of the disorder is acute and self-limited in 80 percent of cases, whereas at least 80 percent of cases in adults are chronic. Splenectomy produces a long-term remission or cure in approximately two thirds of patients,1-3,5-7 but surgery is seldom performed in young children because of the risk of septicemia and cannot be performed in some elderly patients with other medical problems. Vaccination against encapsulated organisms19 and laparoscopic splenectomy20 have dramatically reduced the morbidity associated with the procedure. Consequently, splenectomy is now feasible for a relatively large proportion of children and adults with idiopathic thrombocytopenic purpura. Nonetheless, it is not without adverse effects, even when performed at centers with extensive experience.5,6 A way of predicting the response to splenectomy would therefore be helpful in making treatment decisions.
High-dose intravenous immune globulin temporarily elevates the platelet count in many patients with idiopathic thrombocytopenic purpura.14-18 One mechanism underlying this effect is the blockade of Fc receptors on phagocytic cells in the spleen.14-17 Theoretically, high-dose intravenous immune globulin produces the equivalent of a temporary medical splenectomy, which suggests that the response to this treatment can predict the response to surgical splenectomy.
In the 30 patients in our study, the responses to intravenous immune globulin were similar to the responses to splenectomy. All nine patients who had poor responses to intravenous immune globulin also had poor responses to splenectomy. These nine patients subsequently required intermittent or continuous medical therapy to maintain their platelet counts at a level above 50,000 per cubic millimeter. Of the 21 patients who had good or excellent responses to intravenous immune globulin, 19 also had good or excellent responses to splenectomy. Our retrospective study is too small to allow conclusions about differences in responses between adults and children with idiopathic thrombocytopenic purpura.
We suggest that physicians consider early splenectomy rather than a long-term course of corticosteroids for patients with good or excellent responses to intravenous immune globulin. Perhaps the response to high-dose intravenous immune globulin can also be used to make decisions about treatment in young and elderly patients, in whom splenectomy is frequently deferred because of concern about the risk associated with surgery or the immunologic consequences.
Supported by a grant from the Medical Research Council of Canada.
Source Information
From the Departments of Surgery (C.L., M.M., P.T.), Pathology (N.H., J.G.K.), and Medicine (J.G.K.), McMaster University and the Hamilton Health Sciences Corporation, Hamilton, Ont., Canada.
Address reprint requests to Dr. Kelton at Rm. 3W10, McMaster University Medical Centre, 1200 Main St. W., Hamilton, ON L8N 3Z5, Canada.
- References
References
1
George JN ,El-Harake MA ,Raskob GE . Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1994;331:1207-1211
Full Text | Web of Science | Medline2
Bussel JB . Autoimmune thrombocytopenic purpura. Hematol Oncol Clin North Am 1990;4:179-191
Web of Science | Medline3
George JN ,Woolf SH ,Raskob GE , et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996;88:3-40
Web of Science | Medline4
Siegel RS ,Rae JL ,Barth S , et al. Platelet survival and turnover: important factors in predicting response to splenectomy in immune thrombocytopenic purpura. Am J Hematol 1989;30:206-212
CrossRef | Web of Science | Medline5
Jacobs P ,Wood L ,Dent DM . Results of treatment in immune thrombocytopenia. Q J Med 1986;58:153-165
Web of Science | Medline6
Pizzuto J ,Ambriz R . Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American Group on Hemostasis and Thrombosis. Blood 1984;64:1179-1183
Web of Science | Medline7
Ben-Yehuda D ,Gillis S ,Eldor A . Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura. Acta Haematol 1994;91:1-6
CrossRef | Web of Science | Medline8
Coon WW . Splenectomy for idiopathic thrombocytopenic purpura. Surg Gynecol Obstet 1987;164:225-229
Web of Science | Medline9
Brennan MF ,Rappeport JM ,Moloney WC ,Wilson RE . Correlation between response to corticosteroids and splenectomy for adult idiopathic thrombocytopenic purpura. Am J Surg 1975;129:490-492
CrossRef | Web of Science | Medline10
Najean Y ,Dufour V ,Rain JD ,Toubert ME . The site of platelet destruction in thrombocytopenic purpura as a predictive index of the efficacy of splenectomy. Br J Haematol 1991;79:271-276
CrossRef | Web of Science | Medline11
Fabris F ,Zanatta N ,Casonato A ,Randi ML ,Luzzatto G ,Girolami A . Response to splenectomy in idiopathic thrombocytopenic purpura: prognostic value of the clinical and laboratory evaluation. Acta Haematol 1989;81:28-33
CrossRef | Web of Science | Medline12
Julia A ,Araguas C ,Rossello J , et al. Lack of useful clinical predictors of response to splenectomy in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol 1990;76:250-255
CrossRef | Web of Science | Medline13
Fenaux P ,Caulier MT ,Hirschauer MC ,Beuscart R ,Goudemand J ,Bauters F . Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): a report on 181 cases. Eur J Haematol 1989;42:259-264
CrossRef | Web of Science | Medline14
Fehr J ,Hofmann V ,Kappeler U . Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. N Engl J Med 1982;306:1254-1258
Full Text | Web of Science | Medline15
Bussel JB ,Kimberly RP ,Inman RD , et al. Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura. Blood 1983;62:480-486
Web of Science | Medline16
Kelton JG ,Singer J ,Rodger C ,Gauldie J ,Horsewood P ,Dent P . The concentration of IgG in the serum is a major determinant of Fc-dependent reticuloendothelial function. Blood 1985;66:490-495
Web of Science | Medline17
Kelton JG. The interaction of IgG with reticuloendothelial cells: biological and therapeutic implications. In: Garratty G, ed. Current concepts in transfusion therapy. Arlington, Va.: American Association of Blood Banks, 1985:51-107.
18
Bussel JB ,Hilgartner MW . The use and mechanism of action of intravenous immunoglobulin in the treatment of immune hematologic disease. Br J Haematol 1984;56:1-7
CrossRef | Web of Science | Medline19
Konradsen HB ,Henrichsen J . Pneumococcal infections in splenectomized children are preventable. Acta Paediatr Scand 1991;80:423-427
CrossRef | Web of Science | Medline20
Hashizume M ,Ohta M ,Kishihara F , et al. Laparoscopic splenectomy for idiopathic thrombocytopenic purpura: comparison of laparoscopic surgery and conventional open surgery. Surg Laparosc Endosc 1996;6:129-135
CrossRef | Web of Science | Medline
- Citing Articles (54)
Citing Articles
1
Aamer Aleem. (2011) Durability and factors associated with long term response after splenectomy for primary immune thrombocytopenia (ITP) and outcome of relapsed or refractory patients. Platelets 22:1, 1-6
CrossRef2
Rachael F. Grace, Carolyn M. Bennett, A. Kim Ritchey, Michael Jeng, Courtney D. Thornburg, Michele P. Lambert, Michelle Neier, Michael Recht, Manjusha Kumar, Victor Blanchette, Robert J. Klaassen, George R. Buchanan, Margaret Heisel Kurth, Diane J. Nugent, Alexis A. Thompson, Kimo Stine, Leslie A. Kalish, Ellis J. Neufeld. (2011) Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia. Pediatric Blood & Cancern/a-n/a
CrossRef3
Roberto Stasi, Adrian Newland, Patrick Thornton, Ingrid Pabinger. (2010) Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate. Annals of Hematology 89:12, 1185-1195
CrossRef4
Alina Sesarman, Gestur Vidarsson, Cassian Sitaru. (2010) The neonatal Fc receptor as therapeutic target in IgG-mediated autoimmune diseases. Cellular and Molecular Life Sciences 67:15, 2533-2550
CrossRef5
D. Provan, R. Stasi, A. C. Newland, V. S. Blanchette, P. Bolton-Maggs, J. B. Bussel, B. H. Chong, D. B. Cines, T. B. Gernsheimer, B. Godeau, J. Grainger, I. Greer, B. J. Hunt, P. A. Imbach, G. Lyons, R. McMillan, F. Rodeghiero, M. A. Sanz, M. Tarantino, S. Watson, J. Young, D. J. Kuter. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115:2, 168-186
CrossRef6
James H. Wood, David A. Partrick, Taru Hays, Moritz M. Ziegler. (2010) Predicting response to splenectomy in children with immune thrombocytopenic purpura. Journal of Pediatric Surgery 45:1, 140-144
CrossRef7
Kim B. Luley, Thomas Wagner. (2009) Idiopathische thrombozytopenische Purpura (Morbus Werlhof) und ihre Abgrenzung von anderen thrombozytopenischen hämorrhagischen Diathesen. Medizinische Klinik 104:5, 372-383
CrossRef8
Cindy E. Neunert, Brianna C. Bright, George R. Buchanan. (2008) Severe chronic refractory immune thrombocytopenic purpura during childhood: A survey of physician management. Pediatric Blood & Cancer 51:4, 513-516
CrossRef9
R Sukenik-Halevy, M H. Ellis, M D. Fejgin. (2008) Management of Immune Thrombocytopenic Purpura in Pregnancy. Obstetrical & Gynecological Survey 63:3, 182-188
CrossRef10
So-ichi Suenobu, Kensuke Akiyoshi, Seigo Korematsu, Masahisa Takuma, Hiromu Mori, Tatsuro Izumi. (2008) Indium-111 OXINE scintigram in children with cITP: clinical usefulness for indicating splenectomy. International Journal of Hematology 87:2, 233-235
CrossRef11
Thomas Kühne, Victor Blanchette, George R. Buchanan, Ugo Ramenghi, Hugo Donato, Rienk Y.J. Tamminga, Johannes Rischewski, Willi Berchtold, Paul Imbach, . (2007) Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group. Pediatric Blood & Cancer 49:6, 829-834
CrossRef12
Donald M. Arnold, John G. Kelton. (2007) Current Options for the Treatment of Idiopathic Thrombocytopenic Purpura. Seminars in Hematology 44, S12-S23
CrossRef13
Mark Belletrutti, Kaiser Ali, Dorothy Barnard, Victor Blanchette, Anthony Chan, Michele David, Brian Luke, Victoria Price, Bruce Ritchie, John Wu. (2007) Chronic Immune Thrombocytopenic Purpura in Children. Journal of Pediatric Hematology/Oncology 29:2, 95-100
CrossRef14
Rainer Seitz, Herbert K
nig, Johannes Dodt. 2006. Blood. .
CrossRef15
Ugo Ramenghi, Giovanni Amendola, Loredana Farinasso, Paola Giordano, Giuseppe Loffredo, Bruno Nobili, Silverio Perrotta, Giovanna Russo, Marco Zecca. (2006) Splenectomy in children with chronic ITP: Long-term efficacy and relation between its outcome and responses to previous treatments. Pediatric Blood & Cancer 47:S5, 742-745
CrossRef16
Harry R. Koene. (2006) Critical issues of current and future developments in the treatment of immune thrombocytopenic purpura. Pediatric Blood & Cancer 47:S5, 703-705
CrossRef17
Eva Johansson, Per Engervall, Ola Landgren, Gunnar Grimfors, Susanne Widell, Shahideh Rezai, Magnus Bjorkholm. (2006) Response to splenectomy is durable after a certain point in time in adult patients with chronic immune thrombocytopenic purpura. European Journal of Haematology 77:1, 61-66
CrossRef18
James Bussel, Michael Tarantino. (2006) Review of Therapies for Immune Thrombocytopenic Purpura. Seminars in Hematology 43, S1-S2
CrossRef19
Tingting Wang, Maoqiang Xu, Linxiang Ji, Zhong Chao Han, Renchi Yang. (2005) Splenectomy for adult chronic idiopathic thrombocytopenic purpura: experience from a single center in China. European Journal of Haematology 75:5, 424-429
CrossRef20
K. Beseoglu, U. Germing, W. Gross-Weege. (2005) Splenektomie bei idiopathischer thrombozytopenischer Purpura. Der Chirurg 76:8, 769-776
CrossRef21
Philippe Bierling, Bertrand Godeau. (2005) Intravenous Immunoglobulin for Autoimmune Thrombocytopenic Purpura. Human Immunology 66:4, 387-394
CrossRef22
M.V.G Lacerda, M.A.A Alexandre, P.D Santos, A.R.L Arcanjo, W.D Alecrim, M.G.C Alecrim. (2004) Idiopathic thrombocytopenic purpura due to vivax malaria in the Brazilian Amazon. Acta Tropica 90:2, 187-190
CrossRef23
J. Zimmer, E. Andres, E. Noel, A. Koumarianou, J.-F. Blickle, F. Maloisel. (2004) Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center1. Clinical and Laboratory Haematology 26:2, 137-142
CrossRef24
R. Stasi, D. Provan. (2004) Management of Immune Thrombocytopenic Purpura in Adults. Mayo Clinic Proceedings 79:4, 504-522
CrossRef25
Drew Provan, Adrian Newland. (2003) Idiopathic Thrombocytopenic Purpura in Adults. Journal of Pediatric Hematology/Oncology 25:Supplement 1, S34-S38
CrossRef26
(2003) Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. British Journal of Haematology 120:4, 574-596
CrossRef27
Michael Meurer, Gerald Messer. (2002) Plasmapheresis and intravenous immunoglobulin. Dermatologic Therapy 15:4, 333-339
CrossRef28
Drew Provan, Adrian Newland. (2002) Fifty years of idiopathic thrombocytopenic purpura (ITP): management of refractory itp in adults. British Journal of Haematology 118:4, 933-944
CrossRef29
Andreas M. Kaiser, Thomas W. Umbach, Namir Katkhouda. (2002) Predictors of Outcome After Laparoscopic Splenectomy. Problems in General Surgery 19:3, 95-101
CrossRef30
Michael P. Reilly, Steven E. McKenzie. (2002) Mechanisms of Action of IVIg: Physiology of Fc Receptors. Vox Sanguinis 83, 57-63
CrossRef31
T. Gernsheimer. (2002) Pathophysiology and thrombokinetics in autoimmune thrombocytopenia. Blood Reviews 16:1, 7-8
CrossRef32
J.B. Bussel. (2002) Novel approaches to refractory immune thrombocytopenic purpura. Blood Reviews 16:1, 31-36
CrossRef33
Yasuo MITATE, Esaku ASAKURA, Tomoe MIZUTANI, Minori KATO, Takako ITO, Masahide YAMASAKI, Eriko MORISHITA, Tomotaka YOSHIDA, Masanori SAITO, Kenji AOSHIMA, Sinji MINAMI, Sinji NAKAO. (2002) Japanese Journal of Thrombosis and Hemostasis 13:1, 47-54
CrossRef34
Namir Katkhouda, Sharan Manhas, Thomas W. Umbach, Andreas M. Kaiser. (2001) Laparoscopic Splenectomy. Journal of Laparoendoscopic & Advanced Surgical Techniques 11:6, 383-390
CrossRef35
Klaus Lechner. (2001) MANAGEMENT OF ADULT IMMUNE THROMBOCYTOPENIA. Reviews in Clinical and Experimental Hematology 5:3, 222-235
CrossRef36
N. Katkhouda, S. W. Grant, E. Mavor, M. H. Friedlander, R. V. Lord, K. Achanta, R. Essani, R. Mason. (2001) Predictors of response after laparoscopic splenectomy for immune thrombocytopenic purpura. Surgical Endoscopy 15:5, 484-488
CrossRef37
James B. Bussel, Craig P. Kaufmann, Russell E. Ware, B.M.R. Woloski. (2001) Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti-D and to IV gammaglobulin predict response to subsequent splenectomy?. American Journal of Hematology 67:1, 27-33
CrossRef38
Chul Won Choi, Byung Soo Kim, Jae Hong Seo, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Sang Kyun Sohn, Jae Seok Kim, Dong Gun Shin, Hun Mo Ryoo, Kyung Hee Lee, Je Jung Lee, Ik Joo Chung, Hyeoung Joon Kim, Jae Yong Kwak, Chang Yeol Yim, Jin Seok Ahn, Jung Ae Lee, Young Suk Park. (2001) Response to high-dose intravenous immune globulin as a valuable factor predicting the effect of splenectomy in chronic idiopathic thrombocytopenic purpura patients. American Journal of Hematology 66:3, 197-202
CrossRef39
F. Fabris, T. Tassan, R. Ramon, G. Carraro, M. L. Randi, G. Luzzatto, P. Moschino, A. Girolami. (2001) Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura. British Journal of Haematology 112:3, 637-640
CrossRef40
M. Kuwana, J. Kaburaki, J.P. Pandey, M. Murata, Y. Kawakami, H. Inoko, Y. Ikeda. (2000) HLA class II alleles in Japanese patients with immune thrombocytopenic purpura. Associations with anti-platelet glycoprotein autoantibodies and responses to splenectomy. Tissue Antigens 56:4, 337-343
CrossRef41
J.S. Lilleyman. (2000) Chronic childhood idiopathic thrombocytopenic purpura. Best Practice & Research Clinical Haematology 13:3, 469-483
CrossRef42
Namir Katkhouda, Eli Mavor. (2000) LAPAROSCOPIC SPLENECTOMY. Surgical Clinics of North America 80:4, 1285-1297
CrossRef43
Michael J Marcaccio. (2000) Laparoscopic splenectomy in chronic idiopathic thrombocytopenic purpura. Seminars in Hematology 37:3, 267-274
CrossRef44
Victor Blanchette, Manuel Carcao. (2000) Approach to the investigation and management of immune thrombocytopenic purpura in children. Seminars in Hematology 37:3, 299-314
CrossRef45
Rainer Seitz, Herbert König, Johannes Dodt. 2000. Blood. .
CrossRef46
Michael D Tarantino. (2000) Treatment options for chronic immune (idiopathic) thrombocytopenia purpura in children. Seminars in Hematology 37, 35-41
CrossRef47
James B Bussel. (2000) Splenectomy-sparing strategies for the treatment and long-term maintenance of chronic idiopathic (immune) thrombocytopenic purpura. Seminars in Hematology 37, 1-4
CrossRef48
M. Ruivard, M. T. Caulier, J. M. Vantelon, O. Tournilhac, A. Schaeffer, B. Godeau, P. Bierling. (1999) The response to high-dose intravenous immunoglobulin or steroids is not predictive of outcome after splenectomy in adults with autoimmune thrombocytopenic purpura. British Journal of Haematology 105:4, 1130-1132
CrossRef49
John S. Lilleyman. (1999) Management of childhood idiopathic thrombocytopenic purpura. British Journal of Haematology 105:4, 871-875
CrossRef50
K L Harold, R T Schlinkert, D K Mann, C B Reeder, P Noel, T R Fitch, T A Braich, J K Camoriano. (1999) Long-term results of laparoscopic splenectomy for immune thrombocytopenic purpura.. Mayo Clinic Proceedings 74:1, 37-39
CrossRef51
Haruki Kondo, Takaaki Imamura. (1998) High-dose intravenous immune globulin and the response to splenectomy monitoring with platelet-associated IgG in patients with idiopathic thrombocytopenic purpura. European Journal of Haematology 61:3, 213-215
CrossRef52
(1997) High-Dose Intravenous Immune Globulin and the Response to Splenectomy in Patients with Idiopathic Thrombocytopenic Purpura. New England Journal of Medicine 337:15, 1087-1089
Full Text53
SJ Proctor, AP Crossley, JE Calvert, AM Dickinson. (1997) Autoimmune (idiopathic) thrombocytopenic purpura. The Lancet 350:9074, 368
CrossRef54
Simon Hauser. (1997) Autoimmune (idiopathic) thrombocytopenic purpura. The Lancet 350:9074, 368
CrossRef
- Letters
