ABSTRACT
Childhood immune thrombocytopenia (ITP) is generally a benign self-limiting disorder of young children with <10% of cases requiring regular platelet enhancing therapy at 1 year following diagnosis. Increasingly, children with newly diagnosed ITP, who have isolated thrombocytopenia and no atypical features in the history or physical examination, are managed with minimal investigation and observation alone. The role of up-front, short-course corticosteroid therapy without bone marrow aspiration in this subgroup of cases merits further investigation. For children with clinically significant chronic ITP, the timing of elective splenectomy and the role of splenectomy-sparing strategies such as rituximab continues to be debated. Management of children with combined autoimmune cytopenias secondary to systemic lupus erythematosus, common variable immunodeficiency, and the autoimmune lymphoproliferative syndrome is often a challenge. Splenectomy should be avoided in cases with documented immunodeficiencies because of the increased risk of overwhelming sepsis postsplenectomy. For these cases, as well as for children with resistant primary chronic ITP who have failed splenectomy, the role of therapies such as mycophenolate mofetil, sirolimus, and the thrombopoietins remains to be determined.
KEYWORDS
Immune thrombocytopenic purpura - immune thrombocytopenia - children
REFERENCES
-
1
Cines D B, Blanchette V S.
Immune thrombocytopenic purpura.
N Engl J Med.
2002;
346
(13)
995-1008
-
2
Nugent D, McMillan R, Nichol J L, Slichter S J.
Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production.
Br J Haematol.
2009;
146
(6)
585-596
-
3
George J N, Woolf S H, Raskob G E et al..
Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology.
Blood.
1996;
88
(1)
3-40
-
4
Provan D, Newland A, Norfolk D British Committee for Standards in Haematology General Haematology Task Force et al.
Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy.
Br J Haematol.
2003;
120
(4)
574-596
-
5
Provan D, Stasi R, Newland A C et al..
International consensus report on the investigation and management of primary immune thrombocytopenia.
Blood.
2010;
115
(2)
168-186
-
6
Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther M.
American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia.
Blood.
2011;
117
(16)
4190-4207
-
7
Blanchette V S, Carcao M.
Childhood acute immune thrombocytopenic purpura: 20 years later.
Semin Thromb Hemost.
2003;
29
(6)
605-617
-
8
Blanchette V S, Price V.
Childhood chronic immune thrombocytopenic purpura: unresolved issues.
J Pediatr Hematol Oncol.
2003;
25
(Suppl 1)
S28-S33
-
9
Blanchette V, Bolton-Maggs P.
Childhood immune thrombocytopenic purpura: diagnosis and management.
Pediatr Clin North Am.
2008;
55
(2)
393-420
-
10
Rodeghiero F, Stasi R, Gernsheimer T et al..
Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group.
Blood.
2009;
113
(11)
2386-2393
-
11
Stasi R, Amadori S, Osborn J, Newland A C, Provan D.
Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia.
PLoS Med.
2006;
3
(3)
e24
-
12
Dubansky A S, Boyett J M, Falletta J et al..
Isolated thrombocytopenia in children with acute lymphoblastic leukemia: a rare event in a Pediatric Oncology Group Study.
Pediatrics.
1989;
84
(6)
1068-1071
-
13
Calpin C, Dick P, Poon A, Feldman W.
Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura to rule out leukemia?.
Arch Pediatr Adolesc Med.
1998;
152
(4)
345-347
-
14
Kühne T, Buchanan G R, Zimmerman S Intercontinental Childhood ITP Study Group et al.
A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group.
J Pediatr.
2003;
143
(5)
605-608
-
15
Imbach P, Kühne T, Müller D et al..
Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).
Pediatr Blood Cancer.
2006;
46
(3)
351-356
-
16
Lilleyman J S. Paediatric Haematology Forum of the British Society for Haematology .
Intracranial haemorrhage in idiopathic thrombocytopenic purpura.
Arch Dis Child.
1994;
71
(3)
251-253
-
17
Kühne T, Imbach P, Bolton-Maggs PHB, Berchtold W, Blanchette V, Buchanan G R. Intercontinental Childhood ITP Study Group .
Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study.
Lancet.
2001;
358
(9299)
2122-2125
-
18
Woerner S J, Abildgaard C F, French B N.
Intracranial hemorrhage in children with idiopathic thrombocytopenic purpura.
Pediatrics.
1981;
67
(4)
453-460
-
19
Butros L J, Bussel J B.
Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis.
J Pediatr Hematol Oncol.
2003;
25
(8)
660-664
-
20
Neunert C E, Buchanan G R, Imbach P Intercontinental Childhood ITP Study Group Registry II Participants et al.
Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura.
Blood.
2008;
112
(10)
4003-4008
-
21
Blanchette V, Imbach P, Andrew M et al..
Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.
Lancet.
1994;
344
(8924)
703-707
-
22
Carcao M D, Zipursky A, Butchart S, Leaker M, Blanchette V S.
Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP).
Acta Paediatr Suppl.
1998;
424
71-74
-
23
Tarantino M D, Young G, Bertolone S J Acute ITP Study Group et al.
Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children.
J Pediatr.
2006;
148
(4)
489-494
-
24
Buchanan G R, Holtkamp C A.
Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura. A randomized clinical trial.
Am J Pediatr Hematol Oncol.
1984;
6
(4)
355-361
-
25
Blanchette V S, Luke B, Andrew M et al..
A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura.
J Pediatr.
1993;
123
(6)
989-995
-
26
Gaines A R.
Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.
Blood.
2005;
106
(5)
1532-1537
-
27
Imbach P, Akatsuka J, Blanchette V et al..
Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.
Eur J Pediatr.
1995;
154
(9, Suppl 4)
S60-S64
-
28
Sobota A, Neufeld E J, Lapsia S, Bennett C M.
Response to mercaptopurine for refractory autoimmune cytopenias in children.
Pediatr Blood Cancer.
2009;
52
(1)
80-84
-
29
Hilgartner M W, Lanzkowsky P, Smith C H.
The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children.
Acta Paediatr Scand.
1970;
59
(4)
409-415
-
30
Quiquandon I, Fenaux P, Caulier M T, Pagniez D, Huart J J, Bauters F.
Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases.
Br J Haematol.
1990;
74
(2)
223-228
-
31
Andersen J C.
Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy.
N Engl J Med.
1994;
330
(22)
1560-1564
-
32
Kühne T, Freedman J, Semple J W, Doyle J, Butchart S, Blanchette V S.
Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura.
J Pediatr.
1997;
130
(1)
17-24
-
33
Cuker A, Cines D B.
Immune thrombocytopenia.
Hematology (Am Soc Hematol Educ Program).
2010;
2010
377-384
http://asheducationbook.hematology.org
-
34
Arnold D M, Dentali F, Crowther M A et al..
Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura.
Ann Intern Med.
2007;
146
(1)
25-33
-
35
Bennett C M, Rogers Z R, Kinnamon D D Pediatric Rituximab/ITP Study Group and the Glaser Pediatric Research Network et al.
Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura.
Blood.
2006;
107
(7)
2639-2642
-
36
Mueller B U, Bennett C M, Feldman H A Pediatric Rituximab/ITP Study Group et al.
One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab.
Pediatr Blood Cancer.
2009;
52
(2)
259-262
-
37
Carson K R, Evens A M, Richey E A et al..
Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project.
Blood.
2009;
113
(20)
4834-4840
-
38
Kaushansky K.
Thrombopoietin.
N Engl J Med.
1998;
339
746-754
-
39
Kaushansky K.
Historical review: megakaryopoiesis and thrombopoiesis.
Blood.
2008;
111
(3)
981-986
-
40
Bussel J B, Kuter D J, Pullarkat V, Lyons R M, Guo M, Nichol J L.
Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP.
Blood.
2009;
113
(10)
2161-2171
-
41
Kuter D J, Rummel M, Boccia R et al..
Romiplostim or standard of care in patients with immune thrombocytopenia.
N Engl J Med.
2010;
363
(20)
1889-1899
-
42
Bussel J B, Cheng G, Saleh M N et al..
Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.
N Engl J Med.
2007;
357
(22)
2237-2247
-
43
Price V E, Dutta S, Blanchette V S et al..
The prevention and treatment of bacterial infections in children with asplenia or hyposplenia: practice considerations at the Hospital for Sick Children, Toronto.
Pediatr Blood Cancer.
2006;
46
(5)
597-603
-
44
Crary S E, Buchanan G R.
Vascular complications after splenectomy for hematologic disorders.
Blood.
2009;
114
(14)
2861-2868
-
45
van Hoff J, Ritchey A K.
Pulse methylprednisolone therapy for acute childhood idiopathic thrombocytopenic purpura.
J Pediatr.
1988;
113
(3)
563-566
-
46
Shatz D V, Schinsky M F, Pais L B, Romero-Steiner S, Kirton O C, Carlone G M.
Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy.
J Trauma.
1998;
44
(5)
760-765, discussion 765–766
-
47
Williams J A, Boxer L A.
Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents.
J Pediatr Hematol Oncol.
2003;
25
(3)
232-235
-
48
Arnold D M, Nazi I, Santos A et al..
Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura.
Blood.
2010;
115
(1)
29-31
-
49
Cunningham-Rundles C.
How I treat common variable immune deficiency.
Blood.
2010;
116
(1)
7-15
-
50
Teachey D T, Seif A E, Grupp S A.
Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS).
Br J Haematol.
2010;
148
(2)
205-216
-
51
Oliveira J B, Bleesing J J, Dianzani U et al..
Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop.
Blood.
2010;
116
(14)
e35-e40
-
52
Rao V K, Dugan F, Dale J K et al..
Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome.
Br J Haematol.
2005;
129
(4)
534-538
-
53
Teachey D T, Greiner R, Seif A et al..
Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome.
Br J Haematol.
2009;
145
(1)
101-106
-
54
Seif A E, Manno C S, Sheen C, Grupp S A, Teachey D T.
Identifying autoimmune lymphoproliferative syndrome in children with Evans syndrome: a multi-institutional study.
Blood.
2010;
115
(11)
2142-2145
-
55
Beck C E, Nathan P C, Parkin P C, Blanchette V S, Macarthur C.
Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in children: a systematic review and meta-analysis of randomized controlled trials.
J Pediatr.
2005;
147
(4)
521-527
-
56
Tamminga R, Berchtold W, Bruin M, Buchanan G R, Kühne T.
Possible lower rate of chronic ITP after IVIG for acute childhood ITP an analysis from registry I of the Intercontinental Cooperative ITP Study Group (ICIS).
Br J Haematol.
2009;
146
(2)
180-184
-
57
Najean Y, Rain J D, Billotey C.
The site of destruction of autologous 111In-labelled platelets and the efficiency of splenectomy in children and adults with idiopathic thrombocytopenic purpura: a study of 578 patients with 268 splenectomies.
Br J Haematol.
1997;
97
(3)
547-550
-
58
Cuker A, Cines D B.
Evidence-based mini-review: Is indium-labeled autologous platelet scanning predictive of response to splenectomy in patients with chronic immune thrombocytopenia?.
Hematology (Am Soc Hematol Educ Program).
2010;
2010
385-386
http://asheducationbook.hematology.org
-
59
Buchanan G R, Adix L.
Grading of hemorrhage in children with idiopathic thrombocytopenic purpura.
J Pediatr.
2002;
141
(5)
683-688
-
60
Klaassen R J, Blanchette V S, Barnard D et al..
Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools.
J Pediatr.
2007;
150
(5)
510-515, 515, e1
-
61
Mathias S D, Bussel J B, George J N, McMillan R, Okano G J, Nichol J L.
A disease-specific measure of health-related quality of life for use in adults with immune thrombocytopenic purpura: its development and validation.
Health Qual Life Outcomes.
2007;
5
11
-
62
Drachman J G.
Inherited thrombocytopenia: when a low platelet count does not mean ITP.
Blood.
2004;
103
(2)
390-398
-
63
Blanchette V S, Kirby M A, Turner C.
Role of intravenous immunoglobulin G in autoimmune hematologic disorders.
Semin Hematol.
1992;
29
(3, Suppl 2)
72-82
-
64
Ben-Yehuda D, Gillis S, Eldor A. Israeli ITP Study Group .
Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura.
Acta Haematol.
1994;
91
(1)
1-6
-
65
Mantadakis E, Buchanan G R.
Elective splenectomy in children with idiopathic thrombocytopenic purpura.
J Pediatr Hematol Oncol.
2000;
22
(2)
148-153
-
66
Kühne T, Blanchette V, Buchanan G R Intercontinental Childhood ITP Study Group et al.
Splenectomy in children with idiopathic thrombocytopenic purpura: a prospective study of 134 children from the Intercontinental Childhood ITP Study Group.
Pediatr Blood Cancer.
2007;
49
(6)
829-834
Victor S. BlanchetteF.R.C.P.
Medical Director, Pediatric Thrombosis and Hemostasis Program, Division of Hematology/Oncology, Hospital for Sick Children
555 University Avenue, Toronto, ON M5G 1X8, Canada
Email: victor.blanchette@sickkids.ca
