Diagnosis and management of typical, newly diagnosed primary immune thrombocytopenia (ITP) of childhood
Posted: Oct 26 2018
The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.
Jeremy N Friedman, Carolyn E Beck; Canadian Paediatric Society, Acute Care Committee
This practice point applies to children aged 90 days through 17 years who have typical, newly diagnosed primary immune thrombocytopenia (ITP). Current recommendations on management and information from recent studies are summarized with the goal of decreasing variable practice among providers and improving patient-centred care. Options for initially managing young patients with ITP who experience bruising, petechiae or occasional mild epistaxis not interfering with daily living include observation without pharmacotherapy as a first-line option. When active therapy is pursued, choices include the use of corticosteroids and IVIG. Children with moderate or severe bleeding continue to require hospitalization and treatment. Shared decision-making can enhance patient-centred care and ensure that the families have a full understanding of the management options available.
Keywords: Intracranial hemorrhage (ICH); Immune thrombocytopenia (ITP); Intravenous immunoglobulin (IVIG); Shared decision-making (SDM)
Newly diagnosed primary immune thrombocytopenia (ITP) typically occurs in healthy children and is characterized by immune-mediated destruction of otherwise normal platelets. The cause of ITP is not usually known, but the condition can be triggered by a viral infection or other immune phenomenon. ITP affects approximately 5 in 100,000 children per year, most commonly between age 2 to 5 years . Typical natural history is self-resolution within 6 months, which occurs in 75% to 80% of cases , with some of the remaining children resolving within a year of diagnosis . Most children present with mild bruising and petechiae, but approximately 3% present with more serious bleeding from the nose, mucosa or gastrointestinal tract . The most serious complication of ITP is intracranial hemorrhage, which occurs in approximately 0.17% to 0.6% of cases .
Typical ITP can be diagnosed based on classic features of the patient’s history, physical examination and laboratory investigation. Specific ‘red flags’ should signal alternate diagnoses and warrant a hematology consultation (Table 1). By definition, the platelet count in typical ITP is <100 x 109/L, but most cases have a platelet count of <20 x 109/L. In children with typical features of ITP and no red flags, a bone marrow examination to rule out leukemia is not necessary . Secondary causes of ITP include drug-induced, systemic lupus erythematosus and infections or immune-deficiencies, and malignancy needs to be considered if red flags are present. These causes need investigation in children who do not present typically.
How best to manage cases of typical ITP in children remains unclear. Pharmacological treatments increase the platelet count to reduce bleeding or perceived bleeding risk. They are not curative, however, and side effects as well as potential requirement for hospitalization must be considered. While ITP guidelines in the U.K.  have recommended only treating children with significant bleeding symptoms, this practice has not traditionally been followed in North America .
Management options include observation without specific treatment or active therapy with corticosteroids, intravenous immunoglobulin (IVIG) or with anti-D immunoglobulin (anti-D) for Rh-positive children. Whether early treatment affects the risk for life-threatening bleeding complications or for developing chronic ITP is unclear .
This practice point summarizes the most recent recommendations from the American Society of Hematology  and new information from recent studies . Guidance for decision-making is offered  with the goal of decreasing variable practice among health care providers and enhancing patient-centred management of this common childhood condition. Treatment advice applies to children aged 90 days through 17 years who have typical, newly diagnosed primary ITP (up to 3 months post-diagnosis). This practice point does not address persistent, chronic or secondary ITP .
New research and guidance
In 2011, the American Society of Hematology (ASH) released a clinical practice guideline on the evaluation and management of ITP . For typical ITP, the guideline suggested an approach aimed at achieving a platelet count associated with adequate hemostasis (i.e., with no active bleeding, specifically no epistaxis, menorrhagia or blood in stools), rather than attaining an absolute number, while involving the patient and family in treatment decisions. Most children with no bleeding or only mild bleeding (petechiae and/or bruising; an estimated 77% of cases) can be managed using observation alone, regardless of platelet count. This recommendation aligned with international guidelines , and was based both on the relative rarity of significant bleeding and lack of evidence that treatment decreases risk for severe bleeding or for developing chronic ITP . The recommendation to move away from platelet count as a surrogate marker for hemostasis and toward observation as the preferred management option marked a shift from previous practice in North America.
Before publication of the 2011 guidelines, children hospitalized for typical, newly diagnosed ITP in the United States usually received IVIG treatment (i.e., in approximately 78% of cases) . One recent study indicated poor uptake of the guidelines. Out of 4,937 children with ITP, the number receiving pharmacological treatment increased post-guideline (94.1% versus 92.9%). Of note, only 14% of these children had documented significant bleeding . The tendency to actively treat ITP in the United States contrasts with practice patterns in the U.K., where platelet-raising treatment is used in only 16% of cases .
For children without active bleeding (described clinically in Table 2), strongly consider observation as the first-line approach, with oral corticosteroids or IVIG as second-line options. Involve the family in management decisions and consider multiple factors, including the individual’s bleeding risk (e.g., activity level), logistics (e.g., household distance from hospital) and social issues (e.g., reliability of follow-up). Shared decision-making should incorporate each family’s values and preferences.
For children with moderate bleeding, active therapy continues to be recommended. Treatment options include a single dose of IVIG (0.8 g/kg to 1.0 g/kg) or a short course of corticosteroids . Intravenous anti-D immune globulin (anti-D) can only be used in Rh-positive children and is generally not considered as first-line therapy due to rare but serious adverse effects .
For children with severe bleeding (e.g., prolonged epistaxis, gastrointestinal bleeding or ICH; an estimated 3% of total cases), immediate treatment in hospital with intravenous steroids and IVIG is indicated. Tranexamic acid may help as an adjunct therapy at a dose of 25 mg/kg/dose administered 3 to 4 times per day (to a maximum of 1500 mg per dose or 4500 to 6000 mg per day). Platelet transfusion is generally contraindicated except for acute, life-threatening bleeds or in children requiring immediate surgery.
Shared decision-making in children with ITP 
The relative rarity of severe bleeding with ITP makes it unlikely that future trials will fully establish the risks and benefits of active treatment or alleviate the decisional conflict that exists among providers and families considering treatment options. Decisions remain preference-sensitive because the benefits of any single option do not clearly outweigh potential risks. This uncertainty provides an ideal opportunity for SDM, with discussions among patients, parents and health care providers considering two or more clinically reasonable options and paying explicit attention to family values and preferences. Risk adversity, the desire for inpatient versus outpatient management, and the risks and benefits of each option (e.g., degree of comfort with blood products or corticosteroid side effects, and observation versus active therapy) should be considered. Older children’s personal goals relating to their participation in or return to regular activities after an episode should also be accounted for. Clear, unbiased communication, preferably using educational resources to inform families concerning the pros and cons of management options (Table 3), is essential for effective SDM.
Initial non-responders or early relapse
When pharmacotherapy is used, the goal is to raise platelet counts to a level where hemodynamic stability is achieved. Some experts continue to use a quantitative threshold (i.e., a platelet count >10 or 20 x 109/L) to reduce risk for serious bleeding. For children who do not respond initially, further treatment may involve switching to a different modality (e.g., from IVIG to corticosteroids or vice-versa). Approximately one-third of children who respond to treatment initially, regardless of type, will relapse, with platelet counts falling below 20 x 109/L within 2 to 6 weeks. Retreatment decisions should be based on similar criteria to those initially considered, with modality depending on tolerance of and response to previous treatment agents.
Supportive care and monitoring
All follow-up visits should include a physical examination, checking the platelet count and anticipatory guidance around bleeding signs. Appointments should be regularly scheduled until platelet counts have recovered, with frequency of follow-up depending on the clinical scenario and platelet count. When platelet counts remain low or there is evidence of bleeding, patients must avoid contact sports and activities that may cause injuries, especially to the head. Medications and complementary medicines with anti-platelet activity (e.g., non-steroidal anti-inflammatories and some herbal products) must also be avoided. Dentists and doctors should be reminded of the condition at each visit. Collaboration among community physicians, emergency department staff, hematologists and hospitalist paediatricians is encouraged to build uniformity in evidence-based best practice.
|TABLE 2: Classification of bleeding and management options|
Proportion of cases 
No or mild bleeding
|Data drawn from references  IVIG Intravenous immunoglobulin IV intravenous|
|TABLE 3: Comparison of therapeutic options|
Oral prednisone or dexamethasone (steroids may be given IV)
Dose regimes vary: prednisone 4 mg/kg/day orally (divided twice to four times daily) for 4 days (to a maximum 150 mg/day)  without taper, versus 2 mg/kg/day orally for 1 to 2 weeks, with tapering dose
No evidence to support a longer versus brief course 
0.8 g/kg to 1 g/kg
Consider measuring baseline IG levels for children <1 year of age or when an immune deficiency is suspected
Side-effects and disadvantages
Longer period of activity restriction 
Anxiety while awaiting platelet recovery 
Increased appetite, weight
Gastritis (consider use of stomach protectant)
Hypertension (with a longer course)
Poor taste may affect tolerance
Headache (aseptic meningitis)
Requires IV placement and (at minimum) a one-day stay in hospital
No medication cost
No IV required
75% to 80% will improve within 6 months 
Will take longer for platelet count to rise
Effective in up to 72% to 88% of cases 
Increase in platelets, usually within 48 h
Effective in >80% of cases 
Increase in platelets usually within 24 h; peak response at 2 to 7 days 
Should be used if more rapid increase is required 
|*Only recommended in cases with no or mild bleeding|
|Data drawn from reference  IVIG Intravenous immunoglobulin IV intravenous N/A not applicable|
SickKids Hospital (updated December 2012). Immune thrombocytopenia (ITP): What happens after diagnosis: http://www.aboutkidshealth.ca/En/HealthAZ/ConditionsandDiseases/blooddisorders/Pages/ITP-what-happens-after-diagnosis.aspx
Centre hospitalier universitaire Sainte-Justine, Services d’hématologie et de pédiatrie (July 2013 version). Protocole de prise en charge des thrombopénies immunes aiguës, nouvellement diagnostiquées, au CHU Sainte-Justine: http://www.urgencehsj.ca/wp-content/uploads/thrombop%C3%A9nie.pdf
This practice point was reviewed by the Community Paediatrics Committee and the Emergency Medicine and Hospital Paediatrics Sections of the Canadian Paediatric Society. It was also reviewed by representatives of the Canadian Paediatric Thrombosis and Hemostasis Network, with our thanks.
CANADIAN PAEDIATIC SOCIETY ACUTE CARE COMMITTEE
Members: Carolyn Beck MD, Laurel Chauvin-Kimoff MD (Chair), Kimberly Dow MD (Board Representative), Catherine Farrell MD (past member), Jeremy Friedman MD (past member), Evelyne D. Trottier MD, Kristina Krmpotic MD, Kyle McKenzie MD
Liaisons: Kevin Chan MD, CPS Paediatric Emergency Medicine Section; Marie-Joëlle Doré-Bergeron MD, CPS Hospital Paediatrics Section
Principal authors: Jeremy N Friedman MD, Carolyn E Beck MD
- Witmer CM, Lambert MP, O’Brien SH, Neunert C. Multicenter cohort study comparing U.S. management of inpatient pediatric immune thrombocytopenia to current treatment guidelines. Pediatr Blood Cancer 2016;63(7):1227-31.
- Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117(16):4190-207.
- 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):351-6.
- Neunert CE, Buchanan GR, Imbach P, et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008;112(10):4003-8.
- Kühne T, Buchanan GR, Zimmerman S, 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):605-8.
- Kime C, Klima J, Rose MJ, O’Brien SH. Patterns of inpatient care for newly diagnosed immune thrombocytopenia in US children’s hospitals. Pediatr 2013;131(5):880-5.
- 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):345-7.
- British Committee Standards Haematology (BCSH) General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003;120(4):574-96.
- Treutiger I, Rajantie J, Zeller B, et al. Does treatment of newly diagnosed idiopathic thrombocytopenic purpura reduce morbidity? Arch Dis Child 2007;92(8):704-7.
- Beck CE, Nathan PC, Parkin PC, Blanchette VS, 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):521-7.
- Beck CE, Boydell KM, Stasiulis E, et al. Shared decision making in the management of children with newly diagnosed immune thrombocytopenia. J Pediatr Hematol Oncol 2014;36(7):559-65.
- 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):2386-93.
- Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010;115(2):168-86.
- Grainger JD, Rees JL, Reeves M, Bolton-Maggs PH. Changing trends in the UK management childhood ITP. Arch Dis Child 2012;97(1):8-11.
- Carcao MD, Zipursky A, Butchart S, Leaker M, Blanchette VS. Short-course oral prednisone therapy in children presenting with acute immune thrombocytopenic purpura (ITP). Acta Paediatr Suppl 1998;424:71-4.
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.