1 Immune Thrombocytopenia (ITP) in Children - Pediatric - Inpatient/Ambulatory/Emergency Department External Clinical Practice Guideline Endorsement Note: Active Table of Contents – Click each header below to jump to the section of interest Table of Contents INTRODUCTION .................................................................................................................................3 SCOPE ................................................................................................................................................3 RECOMMENDATIONS .........................................................................................................................4 TABLE 1. SUMMARY OF ASH GUIDELINE RECOMMENDATIONS FOR THE MANAGEMENT OF ITP1,8 ........5 TABLE 2. SUMMARY OF KEY POINTS FOR 1ST AND 2ND LINE MEDICATIONS FOR ITP IN CHILDREN ..........7 METHODOLOGY .................................................................................................................................8 APPENDIX A. MANAGEMENT OF IMMUNE THROMBOCYTOPENIA IN CHILDREN ................................. 11 Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 2 Content Expert(s): Christina Amend, MD – Pediatric Hematology/Oncology Email Address: CAmend@pediatrics.wisc.edu Workgroup Members: Luke Addesso, MD – General Pediatrics Justin Graff, PharmD - Pharmacy Cathy Lee-Miller, MD - Pediatric Hematology/Oncology Mary Mably, RPh – Pharmacy Sarah Mc Dermott, DO, MBS - Pediatric Hematology/Oncology Daniel Sklansky, MD – Pediatric Hospitalist Reviewer(s): Allie Hurst, MD – Emergency Medicine Anne Marsh, MD - Pediatric Hematology/Oncology Contact for Changes: Center for Clinical Knowledge Management (CCKM) Email Address: CCKM@uwhealth.org Guideline Author: Lee Skrupky, PharmD – Center for Clinical Knowledge Management Committee Approval(s): Clinical Knowledge Management (CKM) Council (03/28/24) Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 3 Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disorder in which a low platelet count (<100 x 109/L) results from destruction of existing platelets and impaired production of new platelets. ITP is the most common cause of thrombocytopenia in children, with an estimated incidence of ~2-10 cases per 100,000 children annually (peak incidence between ages 2-5 years)1-5. A typical presentation involves an otherwise healthy child with petechiae, bruising, and/or mild mucosal bleeding. In most pediatric cases, ITP is mild and resolution often occurs without intervention; when treatment is required, approximately three-quarters will respond to 1st line therapies. However, severe bleeding does occur rarely (≤1%) and is the primary concern given the risk of severe morbidity and mortality1-5. ITP can be primary or secondary in nature; primary ITP is when there are no other apparent causes of thrombocytopenia and secondary ITP is when there is an identifiable associated condition1,6,7. Primary ITP makes up the majority (~80%) of cases1,6,7 and is the focus of this guideline. ITP is also categorized based on the duration of thrombocytopenia as follows1: • Newly diagnosed ITP (<3 months duration) • Persistent ITP (3-12 months duration) • Chronic ITP (>12 months duration) In 2019, the American Society of Hematology (ASH) published an update to their 2011 clinical practice guideline8 for the management of ITP in adults and children. This update1 addressed 21 questions based on a review and appraisal of the primary literature through 2017; recommendations 10-21 and 2 good practice statements are specific to the management of children with newly diagnosed ITP. These guidelines are intended to address the management of patients with non-life-threatening bleeding and are noted to exclude emergency management and pregnancy. In this endorsement guideline, we outline recommendations for the management of children with ITP who do not have severe bleeding requiring emergency care. Scope Intended User(s): Physicians, Advanced Practice Providers, Nurses, Pharmacists Objective(s): To provide standardized, evidence-based guidelines for the assessment and management of primary ITP in children Target Population: Children (age 1-17 yrs) with suspected primary ITP Clinical Questions Considered: • When should children with ITP be admitted to the hospital for treatment? • What treatments are recommended for children with newly diagnosed ITP? • What treatments are recommended for children with ITP who do not respond to first-line therapies? Definitions1 Thrombocytopenia: Platelet count <100 x 109/L Newly diagnosed ITP: <3 months duration Persistent ITP: 3-12 months duration Chronic ITP: >12 months duration Minor bleeding: bleeding that involves only cutaneous manifestations (i.e. bruising, petechiae) Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 4 Non-life-threatening mucosal bleeding: Bleeding that involves only mucosal surfaces and does not require emergent transfusion or intervention (i.e. epistaxis, gum bleeding, menorrhagia) Remission: Platelet count >100 x 109/L at 12 months Recommendations Diagnosis As there is no single test that identifies ITP, a diagnosis of primary ITP is established on a clinical basis through a patient history, physical examination, complete blood count and peripheral smear1,3-6,8. A diagnosis of ITP is made when these examinations yield: • isolated thrombocytopenia (<100 x 109/L) on the CBC • no abnormal findings on peripheral smear • an absence of findings that would raise concern for other causes of thrombocytopenia When patients meet the typical criteria outlined above, there is no need to investigate further for potential underlying autoimmune or bone marrow conditions. Therefore, additional tests such as a bone marrow biopsy, antinuclear antibody testing, or immunoglobulin testing are not routinely recommended to establish the diagnosis1,3-6,8 (see Table below for ASH recommendations against such testing in specific scenarios). If atypical features are present or there is concern for other conditions associated with thrombocytopenia (i.e. systemic illness, infection, malignancy, autoimmune illness, medications), consider hematology consultation and additional referrals to help guide further work-up (UW Health Best Practice Statement). Treatment UW Health endorses the recommendations pertaining to children (#10-21) within the American Society of Hematology (ASH) 2019 guidelines1 for immune thrombocytopenia and also the carried over recommendations from 2011 ASH guideline8 that were not changed/updated in 2019. The endorsed ASH Guideline recommendations for the management of children with ITP are summarized in Table 1. Appendix A includes an algorithm that is based on these recommendations, outlining our internal guidance for the management of pediatric ITP. Finally, Table 2 provides a summary of key details for each of the first- and second-line medical therapies for ITP. The decision on whether to treat is not based on platelet count alone but instead takes into consideration the bleeding risk and health-related quality of life (HRQoL) of the patient1,3-6,9. HRQoL is not explicitly defined in the ASH Guideline, but considerations include not only physical health but also mental and social domains; examples from these latter domains may include restrictions on activities, anxiety due to the risk of bleeding, depression, fatigue, and the burden of treatment and monitoring. The overall treatment goals are to keep children safe, resolve bleeding and any symptoms, and minimize lab draws. The frequency of laboratory monitoring will vary according to patient specific considerations including clinical stability, the presence or absence of symptoms (bleeding, fatigue, diminished QOL), platelet count value and trend, and any treatment being used10. Until remission is achieved, labs (i.e. CBC) should generally be considered every 1-4 weeks; more frequent monitoring (i.e. weekly) should be considered when there are symptoms requiring treatment and/or more severe thrombocytopenia, whereas less frequent monitoring (i.e. monthly) is appropriate if the child is asymptomatic and has only moderate thrombocytopenia. Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 5 Platelet transfusions are indicated only in the presence of severe bleeding and life-threatening situations, and are not used to attempt to reach an arbitrary platelet count value3,4,11. While platelets are < 50 x 109/L, children should be on activity restrictions (when feasible) to avoid injury and medications that might adversely affect platelet function and increase bleeding risk (i.e. NSAIDs, aspirin) should be avoided4,10. Table 1. Summary of ASH Guideline Recommendations for the Management of ITP1,8 Topic Recommendations Level Diagnostic (Carried forward from 2011 ASH Guideline) Diagnosis of ITP We recommend: • Bone marrow examination is unnecessary in children and adolescents with the typical features of ITP • Bone marrow examination is not necessary in children who fail IVIG therapy Grade 1B We suggest: • Bone marrow examination is also not necessary in similar patients prior to initiation of treatment with corticosteroids or before splenectomy • Testing for antinuclear antibodies is not necessary in the evaluation of children and adolescents with suspected ITP Grade 2C Testing in treatment nonresponders We recommend against routine testing for H. pylori in children with chronic ITP Grade 1B Management of MMR-associated ITP (Carried forward from 2011 ASH Guideline) MMR vaccine - associated ITP considerations Children with a history of ITP who are unimmunized receive their scheduled first MMR vaccine Grade 1B In children with either nonvaccine or vaccine-related ITP who have already received their first dose of MMR vaccine, vaccine titers can be checked; if the child displays full immunity (90% to 95% of children), then no further MMR vaccine should be given; if the child does not have adequate immunity, then the child should be reimmunized with MMR vaccine at the recommended age. Grade 1B Treatment Setting (From ASH 2019 Guideline) Outpatient vs. Inpatient Management In children with newly diagnosed ITP and a platelet count of <20 x 109/L who have no or mild bleeding (skin manifestations) only, the ASH guideline panel suggests against admission to the hospital rather than outpatient treatment Conditional, Very low certainty of evidence In children with newly diagnosed ITP and a platelet count of ≥20 x 109/L who have no or mild bleeding (skin manifestations) only, the ASH guideline panel suggests against admission to the hospital rather than outpatient treatment Conditional, Very low certainty of evidence The referring physician should ensure that the patient has follow-up with a hematologist within 24 to 72 hours of diagnosis. Good practice statement Medical Management (From ASH 2019 Guideline) Treatment vs. Observation In children with newly diagnosed ITP who have no or minor bleeding, the ASH guideline panel suggests observation rather than corticosteroids Conditional, Very low certainty of evidence Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 6 In children with newly diagnosed ITP who have no or minor bleeding, the ASH guideline panel recommends observation rather than IVIG Strong, Moderate certainty of evidence In children with newly diagnosed ITP who have no or minor bleeding, the ASH guideline panel recommends observation rather than anti-D immunoglobulin Strong, Moderate certainty of evidence Treatment of children with non– life-threatening mucosal bleeding and/or diminished HRQoL In children with newly diagnosed ITP who have non–life- threatening mucosal bleeding and/or diminished HRQoL, the ASH guideline panel suggests corticosteroids rather than anti-D immunoglobulin Conditional, Low certainty of evidence In children with newly diagnosed ITP who have non–life- threatening mucosal bleeding and/or diminished HRQoL, the ASH guideline panel suggests corticosteroids rather than IVIG Conditional, Low certainty of evidence In children with newly diagnosed ITP who have non–life- threatening mucosal bleeding and/or diminished HRQoL [and whom cannot tolerate/receive corticosteroids OR previously failed corticosteroids], the ASH guideline panel suggests either anti-D immunoglobulin or IVIG Conditional, Low certainty of evidence Corticosteroid duration and type In children with newly diagnosed ITP who have non–life- threatening bleeding and/or diminished HRQoL, the ASH guideline panel recommends against courses of corticosteroids longer than 7 days rather than courses 7 days or shorter Strong, Very low certainty of evidence In children with newly diagnosed ITP who have non–life- threatening mucosal bleeding and/or diminished HRQoL, the ASH guideline panel suggests prednisone (2-4 mg/kg per day; maximum, 120 mg daily, for 5-7 days) rather than dexamethasone (0.6 mg/kg per day; maximum, 40 mg per day for 4 days) Conditional, Very low certainty of evidence Management of children with ITP who do not have a response to 1st line treatment In children with ITP who have non–life-threatening mucosal bleeding and/or diminished HRQoL and do not respond to first-line treatment, the ASH guideline panel suggests the use of TPO-RAs rather than rituximab Conditional, Very low certainty of evidence In children with ITP who have non–life-threatening mucosal bleeding and/or diminished HRQoL and do not respond to first-line treatment, the ASH guideline panel suggests TPO- RAs rather than splenectomy Conditional, Very low certainty of evidence In children with ITP who have non–life-threatening mucosal bleeding and/or diminished HRQoL and do not respond to first-line treatment, the ASH guideline panel suggests rituximab rather than splenectomy Conditional, Very low certainty of evidence The treating physician should ensure that the patient has appropriate immunizations prior to splenectomy and that they receive counseling regarding antibiotic prophylaxis following splenectomy. The treating physician should educate the patient on prompt recognition and management of fever and refer to current recommendations on pre- and post-splenectomy care. Good practice statement Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 7 Table 2. Summary of Key Points for 1st and 2nd Line Medications for ITP in Children * Medication information obtained from Lexi-comp® drug monographs except where cited otherwise. Clinical Pearls are based on expert opinions from UW Health subject matter experts. Drug Dosing Information (Assumes normal organ function) Contraindications, Warnings / Precautions, Drug Interactions Adverse Effects (Select common and significant toxicities reported here; refer to Lexi- comp® for complete list) Clinical Pearls (Pearls are based on expert opinions from internal subject matter experts regarding drug selection, patient monitoring) First-line Acute Therapies Prednisone 2-4 mg/kg/day orally (max 120 mg daily) in 3-4 divided doses, for 5-7 days Review in Lexi-comp® Gastritis Insomnia Mood/behavior changes Increased appetite, weight gain Hypertension Hyperglycemia Time to response: 2-7 days Prolonged durations are not recommended and tapers are not needed with short durations. Prednisone is preferred over dexamethasone. IVIG 0.8–1 g/kg IV for 1-2 days3,4,6,11 Alternative Dosing: 400 mg/kg IV for 5 days See UW Health IVIG Guideline for further details regarding pre-medication, infusion rates, monitoring. Review in Lexi-comp® Headache Fever, chills Nausea, vomiting Infusion reactions Hypersensitivity reaction Rare (<1%) possibilities include: Thrombosis, renal failure, hemolytic anemia, and aseptic meningitis Time to response: 1-2 days (usually within 24 hrs) May be preferred when a rapid rise in platelet count is needed and can be used in combination with corticosteroids for more severe cases Anti-D Ig 50–75 mcg/kg over slow IV push (3-5 min) Review in Lexi-comp® Fever, chills Headache Infusion reactions Severe intravascular hemolysis is a rare possibility –monitor for 8h post- infusion Time to response: 1-2 days May be considered as an alternative to IVIG in select patients; Patient must be Rh-positive, DAT-negative, and not splenectomized Second-line Therapies Eltrombopag (TPO receptor agonist) 1–6 y: 25 mg/day orally >6-yrs: 50 mg/day orally (Reduce initial dose to 25 mg once daily if East/Southeast Asian ancestry (e.g., Chinese, Japanese, Korean, Taiwanese) Max dose 75 mg/day Take without a meal or with a meal low in calcium (=50 mg) and ≥ 2 hrs before and 4 hrs after Ca-containing foods or medications/supplements containing Ca, Fe, Al, Mg, Se, or Zn. Review in Lexi-comp® Abdominal pain Diarrhea Headache Arthralgia, myalgia Abnormal hepatic function tests Re-evaluate platelet count in 2 weeks after initiation and use lowest dose that achieves platelet count goal (i.e. >50k) to reduce bleeding. • Eltrombopag: If below goal, increase in 12.5mg-25mg increments bi-weekly to max dose • Romiplostim: If below goal, increase by 1 mcg/kg weekly to max dose Discontinue if platelet count does not respond to a level that avoids clinically important bleeding after 4 weeks at the max daily dose. Thrombocytopenia is likely to recur following treatment cessation, but some (10-30%) may experience sustained response after taper and discontinuation Romiplostim (TPO receptor agonist) Initial 1 mcg/kg subcutaneously once weekly (Dosing range 1-10 mcg/kg weekly) Review in Lexi-comp® Rash Abdominal pain Diarrhea Headache Arthralgia, myalgia Rituximab 375 mg/m2 IV infusion weekly × 4 doses4,12 Review in Lexi-comp® Headache Fever, Chills Urticaria Serum sickness Progressive multifocal leukoencephalopathy (Rare) Time to response: 3 weeks Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 8 Disclaimer Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem. Conflicts of Interest All guideline workgroup members are expected to follow institutional policies and procedures around conflicts of interest. Actions in which a guideline member discloses a conflict of interest relevant to the guideline topic may include, but is not limited to, abstaining from voting, dismissal during comment and voting period, or recusal from requesting and/or participation in the decision-making process. Methodology Development Process Each guideline is reviewed and updated approximately every 3-5 years, but will vary in consideration of the primary literature and relevant practice changes. All guidelines are developed using the guiding principles, standard processes, and styling outlined in the UW Health Clinical Practice Guideline Resource Guide. This includes expectations for workgroup composition and recruitment strategies, disclosure and management of conflict of interest for participating workgroup members, literature review techniques, evidence grading resources, required approval bodies, and suggestions for communication and implementation. Methods Used to Formulate the Recommendations: Following a review and discussion of the literature, including the available national guidelines, the workgroup members agreed to adopt recommendations pertaining to children developed by American Society of Hematology (ASH)1,8. All recommendations endorsed or developed by the guideline workgroup were reviewed and approved by other stakeholders or committees (as appropriate). As the ASH ITP Guideline1,8 is considered to represent the gold standard for guideline-directed therapy for pediatric ITP by UW Health internal experts, a formal AGREE II guideline appraisal was not completed. Methodology of the ASH 2019 Guideline1 for Immune Thrombocytopenia included an update to their systematic review and appraisal of the evidence (up to May, 2017). The guideline panel (8 adult experts, 5 pediatric experts, 2 methodologists with expertise in ITP, and 2 patient representatives) utilized the GRADE approach to conducting the evidence review and developing recommendations. Following the GRADE approach, the ASH guidelines provide evidence ratings for each of their recommendations in 4 potential categories: High, Moderate, Low, and Very low certainty of evidence. Recommendations are categorized as either “Strong” or “Conditional”1. UW Health-developed guidelines also employ the GRADE approach, and our current corresponding definitions for these categories are outlined below. Table 4 of the ASH 2019 guideline provides the intended interpretations of their recommendation labels for the different intended audiences including patients, clinicians, policy-makers, and researchers. The ASH 2011 Guideline for Immune Thrombocytopenia utilized the following definitions for assigning a strength of recommendation and evidence rating: Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 9 Strength of Recommendation 1 Indicates a high degree of confidence that the desirable outcomes of an intervention exceed the undesirable effects (or vice versa) in most patient populations. 2 Indicates a lower degree of confidence that the desirable outcomes outweigh undesirable outcomes (or vice versa). Quality of Evidence Ratings A The recommendation is supported by consistent evidence from randomized controlled trials (RCTs) or exceptionally strong observational studies B The recommendation is supported by RCTs with important limitations or strong evidence from observational studies C The recommendation is derived from RCTs with serious flaws, weaker observational studies, or indirect evidence GRADE Methodology adapted by UW Health Rating Scheme for the Strength of the Evidence/Recommendations: GRADE Ranking of Evidence High We are confident that the effect in the study reflects the actual effect. Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different. Low The true effect may differ significantly from the estimate. Very Low The true effect is likely to be substantially different from the estimated effect. Very Low - Internal Expert Opinion The true effect is likely to be substantially different from the estimated effect. This category of recommendation for or against a specific intervention is derived strictly from the expert opinions of UW Health healthcare professionals with experience in the relevant specialty(ies). This is used in the absence of published evidence or external opinion addressing the specific intervention. Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 10 GRADE Ratings for Recommendations For or Against Practice Strong (S) Generally should be performed (i.e., the net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.) Conditional (C) May be reasonable to perform (i.e., may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.) Good Practice Statement Generally, should be performed (i.e., the expected benefit of the treatment is substantial, expected costs or risk are minimal, and patient values and circumstances are unlikely to affect the decision.) This classification is used for recommendations that guideline members feel are important and for which there is uniform support, but for which evidence directly assessing the specific intervention (or practice) is not available and is highly unlikely to ever be studied (because it may not be warranted or feasible). Such recommendations may have strong indirect evidence of support Collateral Tools & Resources The following collateral tools and resources support staff execution and performance of the evidence-based guideline recommendations in everyday clinical practice. Metrics % of ITP patients without bleeding or minor bleeding only undergoing period of observation vs. treatment % of children with ITP treated in ambulatory setting % of children with ITP receiving preferred 1st-line therapies Patient Resources Immune Thrombocytopenic Purpura (IRP) [HF 4787] Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 11 Appendix A. Management of Immune Thrombocytopenia in Children Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024 12 References 1. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. Dec 10 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966 2. Neunert C, Heitink-Polle KMJ, Lambert MP. A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group. Br J Haematol. Oct 2023;203(1):17-22. doi:10.1111/bjh.19072 3. Russo G, Parodi E, Farruggia P, et al. Recommendations for the management of acute immune thrombocytopenia in children. A Consensus Conference from the Italian Association of Pediatric Hematology and Oncology. Blood Transfus. Jul 27 2023;doi:10.2450/BloodTransfus.501 4. Singh G, Bansal D, Wright NAM. Immune Thrombocytopenia in Children: Consensus and Controversies. Indian J Pediatr. Feb 2020;87(2):150-157. doi:10.1007/s12098-019- 03155-4 5. Verissimo V, Carter T, Wright H, et al. Australian and New Zealand consensus guideline for paediatric newly diagnosed immune thrombocytopaenia endorsed by Australian New Zealand Children's Haematology and Oncology Group. J Paediatr Child Health. May 2023;59(5):711-717. doi:10.1111/jpc.16395 6. Gafter-Gvili A. Current approaches for the diagnosis and management of immune thrombocytopenia. Eur J Intern Med. Feb 2023;108:18-24. doi:10.1016/j.ejim.2022.11.022 7. Grace RF, Lambert MP. An update on pediatric ITP: differentiating primary ITP, IPD, and PID. Blood. Aug 11 2022;140(6):542-555. doi:10.1182/blood.2020006480 8. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. Apr 21 2011;117(16):4190-207. doi:10.1182/blood-2010-08-302984 9. Kochhar M, Neunert C. Immune thrombocytopenia: A review of upfront treatment strategies. Blood Rev. Sep 2021;49:100822. doi:10.1016/j.blre.2021.100822 10. Friedman JN, Beck CE. Diagnosis and management of typical, newly diagnosed primary immune thrombocytopenia (ITP) of childhood. Paediatr Child Health. Feb 2019;24(1):54- 55. doi:10.1093/pch/pxy197 11. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. Nov 26 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812 12. Liang Y, Zhang L, Gao J, Hu D, Ai Y. Rituximab for children with immune thrombocytopenia: a systematic review. PLoS One. 2012;7(5):e36698. doi:10.1371/journal.pone.0036698 Effective 3/28/2024. Contact CCKM@uwhealth.org for previous versions. Copyright © 2024 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 04/2024