Correspondence

Immune Thrombocytopenic Purpura

N Engl J Med 2002; 347:449-450August 8, 2002

Article

To the Editor:

We were disappointed that the use of pulsed high-dose dexamethasone in patients with chronic, refractory immune thrombocytopenic purpura was not mentioned in the review article on this condition by Cines and Blanchette (March 28 issue).1 We have treated three adults who had relapses of immune thrombocytopenic purpura after splenectomy with six cycles of pulsed high-dose dexamethasone, and two of these patients had complete remission lasting for as long as four years of follow-up (Table 1Table 1Characteristics of Three Patients with Immune Thrombocytopenic Purpura Who Underwent Splenectomy and Were Treated with Dexamethasone after Relapse.). Warner et al.2 refuted the claim that pulsed high-dose dexamethasone has a role in treating chronic immune thrombocytopenic purpura; they studied nine patients, but only three patients received the full six cycles of dexamethasone. Furthermore, only four patients underwent splenectomy before receiving dexamethasone. Given previous data from Andersen3 and the guidelines published by the American Society of Hematology,4 pulsed high-dose dexamethasone should still be in the algorithm for treatment of chronic, refractory immune thrombocytopenic purpura.

Issa Khouri, M.D.
California Pacific Medical Center, San Francisco, CA 94115

Bertrand Tuan, M.D.
Kathleen Grant, M.D.
Pacific Hematology–Oncology Associates, San Francisco, CA 94115
bytuan@pol.net

4 References

1. 1

   Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002;346:995-1008
   Full Text | Web of Science | Medline

2. 2

   Warner M, Wasi P, Couban S, Hayward C, Warkentin T, Kelton JG. Failure of pulse high-dose dexamethasone in chronic idiopathic immune thrombocytopenia. Am J Hematol 1997;54:267-270
   CrossRef | Web of Science | Medline

3. 3

   Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med 1994;330:1560-1564
   Full Text | Web of Science | Medline

4. 4

   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 | Medline

To the Editor:

An important lymphoproliferative disorder was omitted from the discussion of secondary (lymphoproliferative) forms of immune thrombocytopenic purpura. The autoimmune lymphoproliferative syndrome is a genetic disorder of abnormal Fas-mediated lymphocyte apoptosis. This disorder, affecting both children and adults, is characterized by lymphadenopathy, splenomegaly, autoimmune thrombocytopenia, and anemia and carries an increased risk of cancer.1-3

It appears that patients with immune thrombocytopenic purpura associated with the autoimmune lymphoproliferative syndrome have bleeding that requires intervention more often than do patients with the more common presentation of childhood immune thrombocytopenic purpura. Moreover, given the increased risk of lymphoid cancers in patients with the autoimmune lymphoproliferative syndrome, this syndrome should be considered before immunosuppressive or cytotoxic agents are used to treat chronic or refractory thrombocytopenia.

Jack J.H. Bleesing, M.D.
Arkansas Children's Hospital, Little Rock, AR 72202
bleesingjacobh@uams.edu

Thomas A. Fleisher, M.D.
National Institutes of Health, Bethesda, MD 20892

3 References

1. 1

   Fisher GH, Rosenberg FJ, Straus SE, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 1995;81:935-946
   CrossRef | Web of Science | Medline

2. 2

   Bleesing JJH, Straus SE, Fleisher TA. Autoimmune lymphoproliferative syndrome: a human disorder of abnormal lymphocyte survival. Pediatr Clin North Am 2000;47:1291-1310
   CrossRef | Web of Science | Medline

3. 3

   Straus SE, Jaffe ES, Puck JM, et al. The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. Blood 2001;98:194-200
   CrossRef | Web of Science | Medline

To the Editor:

The review by Cines and Blanchette unfortunately omitted mention of the devastating effects of transplanting the livers of adults with immune thrombocytopenic purpura.1,2 In a case we described in 1990, a liver donor who had had this condition for 26 years died of spontaneous intracranial hemorrhage. After transplantation, immune thrombocytopenic purpura immediately developed in the recipient, who eventually required the emergency transplantation of a second liver to resolve the profound and life-threatening thrombocytopenia. Since immune thrombocytopenic purpura is relatively common, affecting about 50 of every 1 million adults, our experience should be borne in mind by those evaluating potential liver donors.

Leo J. McCarthy, M.D.
Indiana University Hospital, Indianapolis, IN 46202
lmmcarth@iupui.edu

Walter Dzik, M.D.
Massachusetts General Hospital, Boston, MA 02114

2 References

1. 1

   Friend PJ, McCarthy LJ, Filo RS, et al. Transmission of idiopathic (autoimmune) thrombocytopenic purpura by liver transplantation. N Engl J Med 1990;323:807-811
   Full Text | Web of Science | Medline

2. 2

   Kuo PC, Lewis WD, Dzik W, Jenkins RL. Immune thrombocytopenic purpura following orthotopic liver transplantation. Clin Transplant 1993;7:43-46
   Web of Science

Author/Editor Response

The authors reply:

To the Editor: Khouri and colleagues report a favorable experience with the use of pulsed high-dose dexamethasone in two of three patients with immune thrombocytopenic purpura. They do not indicate the total number of additional patients who were treated. Enthusiasm for the use of dexamethasone waned soon after its efficacy was first reported by Andersen.1 Our review of 13 subsequently published reports shows that there was a partial or complete response lasting for at least six months in 33 of 135 adults and children with chronic immune thrombocytopenic purpura (24 percent) and that a similar number were unable to continue treatment because of toxic effects. The response rates appear to be even lower among adults with long-standing refractory disease.2 High doses of glucocorticoids have long been part of the emergency treatment of patients with chronic immune thrombocytopenic purpura and are described in Figure 5 of our article as part of the management of refractory disease. A controlled study will be required in order to determine whether pulsed dexamethasone differs from other glucocorticoids or favorably alters the long-term outcome of immune thrombocytopenic purpura.

Bleesing and Fleisher report that immune thrombocytopenic purpura in association with the autoimmune lymphoproliferative syndrome poses special issues for management. We concur that immune thrombocytopenic purpura arising in the context of this or other immune, neoplastic, or endocrine disorders often differs in its natural history and management3 from primary immune thrombocytopenic purpura, which was the topic of our review.

McCarthy and Dzik describe an informative case in which immune thrombocytopenic purpura was transmitted by liver donation. More commonly, the condition develops in the recipient of a solid-organ transplant or an allogeneic or autologous bone marrow or stem-cell transplant without evidence that the antibody originated in the donor B cells. No predictive markers have been identified, the pathophysiology is not well characterized, and some cases have been refractory to treatment.4,5

Douglas B. Cines, M.D.
University of Pennsylvania, Philadelphia, PA 19104
dcines@mail.med.upenn.edu

Victor S. Blanchette, M.B., B.Chir.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

5 References

1. 1

   Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med 1994;330:1560-1564
   Full Text | Web of Science | Medline

2. 2

   Chong BH, Keng TB. Advances in the diagnosis of idiopathic thrombocytopenic purpura. Semin Hematol 2000;37:249-260
   CrossRef | Web of Science | Medline

3. 3

   Bussel J, Cines DB. Idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and post-transfusion purpura. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al., eds. Hematology: Basic principles and practice. 3rd ed. Philadelphia: Churchill Livingstone, 2000:2096-114.
   

4. 4

   Jillela AP, Kallab AM, Kutlar A. Autoimmune thrombocytopenia following autologous hematopoietic cell transplantation: review of literature and treatment options. Bone Marrow Transplant 2000;26:925-927
   CrossRef | Web of Science | Medline

5. 5

   Kita Y, Harihara Y, Hirata M, et al. Splenectomy for idiopathic thrombocytopenic purpura after living-related donor transplantation. Transplantation 2000;70:553-555
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Jin Ah Yoon, Chan Kyu Kim, Se Hyung Kim, Kyung Ha Kim, Hyun Jung Kim, Sung Kyu Park, Sang Chul Lee, Nam Su Lee, Sang Byung Bae, Kyu Taek Lee, Jong Ho Won, Hee Sook Park, Dae Sik Hong. (2009) Initial Therapy with High-Dose Dexamethasone for Patients with Idiopathic Thrombocytopenic Purpura. The Korean Journal of Hematology 44:1, 22
   CrossRef

2. 2

   Taro Horino, Atsushi Sasaoka, Toshihiro Takao, Takafumi Taguchi, Hiroshi Maruyama, Hiroyuki Ito, Shigeki Takemoto, Hirokuni Taguchi, Kozo Hashimoto. (2005) Immune thrombocytopenic purpura associated with rheumatoid arthritis: case report. Clinical Rheumatology 24:6, 641-644
   CrossRef

3. 3

   Cheng, Yunfeng, Wong, Raymond S.M., Soo, Yannie O.Y., Chui, Chung Hin, Lau, Fung Yi, Chan, Natalie P.H., Wong, Wai Shan, Cheng, Gregory, . (2003) Initial Treatment of Immune Thrombocytopenic Purpura with High-Dose Dexamethasone. New England Journal of Medicine 349:9, 831-836
   Full Text