First- and second-line treatment options for children with immune thrombocytopenia (ITP)

Treatment	Initial response* (days)^[1]	Peak response^¶ (days)^[1]	Initial response rate	Toxicities/risks	Sustained response
First-line options for newly diagnosed or persistent ITP
Watchful waiting	A few days to 3 to 6 months		Spontaneous complete remission occurs in 50% within one month of presentation and 75% by six months	Risk of preventable hemorrhage (low risk); need for activity restriction; familial anxiety.	Relapse after spontaneous remission is unlikely.
IVIG^Δ Life-threatening bleeding: 1 gram/kg per day IV for one to three days Non-life-threatening bleeding: 0.8 to 1 gram/kg IV, as a single dose	1 to 3	2 to 7	Initially effective in >80% of patients	Side effects include headache (can be severe [eg, aseptic meningitis]), nausea, vomiting, fever, chills, body aches. These can be minimized with premedication and prolonging infusion time.^Δ Transient neutropenia also may occur.	One-third of patients fall below acceptable platelet threshold after 2 to 6 weeks.
Anti-D^Δ^◊ 75 micrograms/kg IV, as a single dose	1 to 3	3 to 7	Initially effective in 70 to 80%	Headache (less common than with IVIG), fever, chills, nausea, and vomiting. Side effects may be reduced with premedication.^Δ Mild hemolysis is common (eg, fall in hemoglobin by 1 to 2 g/dL). DIC and severe hemolysis or renal failure may rarely occur. Anti-D is contraindicated in patients who are Rh-negative or DAT-positive, or have had splenectomy.	Similar to IVIG, although longer responses have been described with repeat dosing.
Methylprednisolone 30 mg/kg as a single daily dose IV for 3 to 4 days (maximum 1000 mg per day)	2 to 14	7 to 28	Initially effective in 75 to 80%	Behavioral change, sleep disturbance, hypertension, impaired glucose tolerance.	In one-quarter to one-third of patients, platelet counts fall below acceptable thresholds after 2 to 6 weeks.
Prednisone 4 mg/kg per day orally for 7 days, followed by rapid tapering^§ (maximum 240 mg/day)	4 to 14	7 to 28	Initially effective in up to 75%	Same as for methylprednisolone above. Prolonged usage may cause weight gain, osteopenia, cataracts, and growth failure.	In many patients, platelet counts fall below acceptable platelet thresholds after tapering, unless the course of prednisone is prolonged.
Dexamethasone 24 mg/m² for 4 days orally or IV^§ (maximum 40 mg/day)	2 to 14	4 to 28	Initially effective in up to 75%	Same as for methylprednisolone above.	In one-third of patients, platelet counts fall below acceptable thresholds after 2 to 6 weeks.
Second-line options for chronic ITP
Rituximab^[3] 375 mg/m² weekly for four weeks	7 to 56	14 to 180	Initial response in 40 to 50%	Urticarial rash, headache, fever, and chills (mild and transient). Serum sickness in up to 10% of children.	25% long-term response (2 or more years after treatment).
Thrombopoietin receptor agonists (eg, eltrombopag^[4], romiplostim^[5])^¥	5 to 7	Not established	Approximately 80% of patients achieve a response	Transaminitis, mild respiratory illness, headache, epistaxis, cataract (rare).	The response lasts only as long as the drug is continued; these drugs do not typically induce remission.
Splenectomy	1 to 56	7 to 56	60 to 70% long-term response	Complications include sepsis and portal vein thrombosis.	70 to 80% of responders maintain platelet response over 4 years.

Refer to UpToDate topic on the treatment of ITP in children for details of our approach to the initial and subsequent treatment of ITP and the overall efficacy of these treatments.

IVIG: intravenous immune globulin; IV: intravenously; Anti-D: anti-Rho (D) immunoglobulin; DIC: disseminated intravascular coagulation; DAT: direct antiglobulin test (also known as direct Coombs test).
* Initial response is the first time that a response could be reasonably expected.
¶ Peak response is the time after which a response becomes less likely at typically used doses. These data do not address the quality of the response (ie, absolute platelet count reached or percent increase from baseline) or the likelihood of a response for any given treatment.
Δ When treating with either IVIG or anti-D, acetaminophen and/or diphenhydramine may be administered as premedication to minimize side effects. In our practice, we also coadminister a single dose of methylprednisolone 30 mg/kg (up to 1 gram maximum) to increase efficacy and to minimize side effects (especially headache).
◊ Anti-D should not be used in in patients who are Rh-negative or those with a positive DAT, unless this result is attributable to recent administration of anti-D. Anti-D should generally not be used in splenectomized patients because it is not effective in this group. However, in patients with severe bleeding, anti-D may be a useful part of combination therapy, even in splenectomized patients, despite its relative lack of efficacy when used as the sole agent in these patients. Anti-D should be used with care in patients with substantial comorbidities or who have evidence of anemia or hemolysis.
§ For treatment with glucocorticoids, a variety of regimens have been used effectively. In our practice, we generally administer glucocorticoids as a short course at a very high dose to minimize toxicity associated with long-term use and because of a potentially more rapid onset of action. Refer to UpToDate topics on management of ITP in children for additional details.
¥ Thrombopoietin receptor agonists are not established treatments for children with ITP. Pediatric dosing has not been established. Refer to UpToDate topics on treatment of ITP in children for additional details.

Additional data from:

Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190.
Beck CE, Nathan PC, Parkin PC, et al. 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; 147:521.
Patel VL, Mahévas M, Lee SY, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 2012; 119:5989.
Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): A randomised, multicentre, placebo-controlled trial. Lancet 2015; 386:1649.
Bussel JB, Buchanan GR, Nugent DJ, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 2011; 118:28.

Adapted from: Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.

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First- and second-line treatment options for children with immune thrombocytopenia (ITP)