Version July 2025
INTRODUCTION —
Immune thrombocytopenia (ITP) of childhood is characterized by isolated thrombocytopenia (platelet count <100,000/microL, with normal white blood cell count and hemoglobin). The cause of ITP remains unknown in most cases, but it can be triggered by a preceding viral infection. ITP was previously known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura. The current term Immune ThrombocytoPenia preserves the widely recognized acronym "ITP" and acknowledges the immune-mediated mechanism of the disorder while allowing that patients may have little or no signs of purpura or bleeding [1].
ITP in children often resolves spontaneously within three months. A minority of affected children go on to have chronic ITP, which is defined as thrombocytopenia for >12 months since presentation. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Disease course'.)
The treatment and prognosis of chronic ITP and chronic refractory disease in children will be reviewed here. The epidemiology, diagnosis, and initial management of ITP in children are discussed separately. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis" and "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients".)
TERMINOLOGY —
The following terms are used in this topic:
●Primary ITP – ITP in the absence of other causes or disorders that are associated with immune-mediated thrombocytopenia is known as primary ITP and is the main focus of this topic review.
●Secondary ITP – Secondary ITP refers to immune-mediated thrombocytopenia with an underlying cause, including drug-induced, or associated with systemic illness (eg, systemic lupus erythematosus, common variable immunodeficiency, human immunodeficiency virus [HIV]). Secondary causes of immune-mediated thrombocytopenia are reviewed separately. (See "Causes of thrombocytopenia in children", section on 'Immune-mediated causes'.)
Primary ITP is categorized into three phases, depending on the duration of the disease course [1]. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Disease course'.)
●Newly diagnosed ITP – ITP within 3 months from diagnosis
●Persistent ITP – Ongoing ITP between 3 and 12 months from initial diagnosis
●Chronic ITP – ITP lasting more than 12 months
In this terminology schema, there is no "acute" ITP. The clinical features of newly diagnosed, persistent, and chronic ITP are otherwise similar. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Clinical features'.)
The distinction between persistent versus chronic ITP is somewhen arbitrary, though the likelihood of spontaneous remission is higher in the former. (See 'Spontaneous remission' below.)
ITP can also be categorized according to the responsiveness to therapy:
●Chronic refractory ITP – Pediatric chronic refractory ITP is poorly defined [2]. It generally refers to chronic ITP without a lasting response to standard pharmacologic treatments (eg, glucocorticoids, intravenous immune globulin [IVIG], thrombopoietin receptor agonists [TPO-RAs], and/or rituximab). Lack of response has been defined as failure to ever achieve a platelet count of ≥30,000/microL or a doubling of the baseline platelet count [1]. However, the definition is not standardized, and some experts define refractory ITP as failure to respond to at least two second-line therapies from different drug classes (eg, TPO-RAs and rituximab) [2]. (See 'Chronic refractory ITP' below.)
Failure to respond to splenectomy is no longer included in the definition since splenectomy is rarely performed in children with ITP. (See 'Splenectomy' below.)
Management of persistent, chronic, and refractory ITP in children is reviewed here. The management of newly diagnosed ITP is discussed separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients".)
RISK FACTORS FOR CHRONIC ITP —
Approximately 10 to 20 percent of children diagnosed with ITP go on to develop chronic ITP, defined as platelet count <100,000/microL lasting beyond 12 months from the time of presentation [1,3-7].
Factors present at diagnosis — Factors that correlate with increased risk of developing chronic ITP include [3,4,6]:
●Older age
●Less severe thrombocytopenia and/or bleeding symptoms at initial diagnosis
●Insidious onset of symptoms
●Lack of preceding infection or vaccination prior to development of ITP
●Underlying chronic medical conditions (eg, autoimmune disorders, primary immunodeficiencies)
However, these findings do not reliably predict whether chronic ITP will develop in a specific patient. This issue is discussed in greater detail separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Disease course'.)
Genetic factors — Genetic factors may play a role in determining the risk of developing chronic ITP.
●Genes related to immune function – Studies have shown that certain polymorphisms in genes related to immune function (eg, CD28, CTLA4, DNAM1, FCGR2B, ICOS, LAG3, PD1, TIM3, TLR4, TNFSF4) may be associated with lower likelihood of responding to ITP therapies and/or increased likelihood of developing chronic ITP [8-10]. Other studies have demonstrated potentially pathogenic variants in immune-related genes (TNFRSF13B, CARD11, CBL, LRBA, NFKB2, RAG2) in a subset of patients with chronic ITP [11,12]. Most patients in these studies had other signs of primary immunodeficiency (eg, abnormal immunoglobulin levels, recurrent infections, allergic disease).
In the setting of ITP and concomitant autoimmune hemolytic anemia (Evans syndrome), studies have identified underlying genetic abnormalities in >50 percent of affected patients [13]. (See "Autoimmune hemolytic anemia (AIHA) in children: Classification, clinical features, and diagnosis", section on 'Evans syndrome'.)
●Inherited platelet disorders – Some patients labeled as having chronic refractory ITP may actually have an inherited platelet disorder rather than an immune-mediated process. If possible, a previously normal platelet count should be documented to exclude this possibility. Inherited platelet disorders are discussed in greater detail separately. A reported "family history of ITP" is a red flag for a possible inherited platelet disorder. (See "Causes of thrombocytopenia in children", section on 'Inherited platelet disorders' and "Inherited platelet function disorders (IPFDs)".)
ONGOING EVALUATION
●Initial diagnostic evaluation – At the initial presentation, most children with a typical presentation of ITP (table 1) undergo a limited evaluation that includes a focused personal and family history, physical examination, and laboratory testing, as summarized in the table (table 2). A previously normal platelet count should be documented whenever possible. Children with atypical findings (eg, lymphadenopathy, splenomegaly, systemic symptoms, or any abnormalities in the complete blood count [CBC] or peripheral blood smear (table 1)) should promptly undergo further investigation to exclude other causes of thrombocytopenia. The initial diagnostic evaluation is discussed in detail in a separate topic review. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Diagnosis'.)
●Additional evaluation for children who develop persistent or chronic ITP – Additional evaluation is performed both to exclude other causes of persistent thrombocytopenia (eg, bone marrow failure, inherited thrombocytopenia) and to assess for underlying or secondary causes of ITP such as immunodeficiency, chronic infection, or systemic autoimmune/inflammatory disorders (table 3). (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Differential diagnosis'.)
The approach to the evaluation for children with persistent or chronic ITP is not standardized, and practice varies considerably. In our practice, we typically perform the following tests at 6 to 12 months from diagnosis if ITP has not resolved and there are no findings suggestive of a particular etiology:
•Testing for infectious causes – This includes:
-Testing for HIV and hepatitis C in all patients with chronic ITP. (See "Pediatric HIV infection: Diagnostic testing in children younger than 18 months" and "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Initial testing'.)
-Testing for cytomegalovirus (CMV) infection in patients with chronic refractory ITP. If CMV infection is detected, antiviral treatment may restore responsiveness to immunoglobulin therapy, while glucocorticoid and other immunosuppressive treatment may worsen the ITP [14]. (See "Overview of cytomegalovirus (CMV) infections in children", section on 'Laboratory diagnosis'.)
-Testing for Helicobacter pylori depending upon the local prevalence of H. pylori as a cause or contributing factor in chronic ITP (H. pylori is an uncommon cause of pediatric chronic ITP in the United States; it is more prevalent in other countries such as Japan and Italy). (See "Helicobacter pylori: Diagnosis and management in the pediatric patient", section on 'Indications for testing in children'.)
•Assessment of humoral immune function – Immunoglobulin levels and/or antibody response to routine childhood vaccines. We repeat these tests annually in all children with chronic ITP. For children with additional clinical concern for impaired immune function (eg, recurrent infections), additional testing may be warranted, as discussed separately. (See "Approach to the child with recurrent infections".)
•Tests to screen for autoimmune disorders – This includes:
-Thyroid function tests, repeated annually [15]. If abnormal, antithyroid antibodies should be measured. (See "Laboratory assessment of thyroid function".)
-Antiphospholipid antibodies (aPL) and antinuclear antibody (ANA) levels. These tests should be repeated annually in adolescent female patients with chronic ITP since the prevalence of autoimmune disease is particularly high in this group. We also perform aPL testing annually in patients with history of thrombosis and/or prolonged activated partial thromboplastin time (aPTT), since these findings are suggestive of antiphospholipid syndrome. If these tests are positive, additional testing for specific autoantibodies should be performed. (See "Measurement and clinical significance of antinuclear antibodies", section on 'Follow-up evaluation' and "Antiphospholipid syndrome: Diagnosis".)
•Consideration of bone marrow examination – Practice varies regarding performing a bone marrow examination in children with chronic ITP, and the optimal approach is uncertain. In our practice, we perform bone marrow examination (including a biopsy, cytogenetics, and fluorescence in situ hybridization) in patients with chronic ITP who have never had a documented robust response to intravenous immune globulin (IVIG) or another ITP therapy demonstrating that the bone marrow is intact. Other experts may not routinely perform bone marrow examination in this setting. Most experts agree that bone marrow examination is not necessary if the child had a typical presentation (table 1) and responded well to ITP therapies.
GENERAL MEASURES
Supportive care — Supportive care for children with persistent or chronic ITP focuses on minimizing the individual's risk for bleeding and addressing issues that can contribute to impaired quality of life (eg, fatigue and worries about bleeding risks). The components of supportive care are similar to those for children with newly diagnosed ITP:
●If needed, restrict physical activities with significant risk of trauma, especially contact and collision sports. The type of activity that is restricted has not been standardized, and decisions should be individualized in collaboration with the patient and family/caregivers. It is important to not overly restrict participation in sports and other social activities [16].
●Avoid medications with antiplatelet activity, including ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs), unless necessary and the child has previously tolerated them. If NSAIDs or other antiplatelet medications are used frequently, it is reasonable to set a slightly higher goal for maintaining the platelet count.
●For postmenarchal female patients, monitor menstrual bleeding and treat with hormonal therapy, antifibrinolytics, and/or iron supplementation as needed. (See 'Adjunctive therapies' below.)
●Monitor for epistaxis and treat with humidity, antiallergy measures, and antifibrinolytics as needed. (See 'Adjunctive therapies' below.)
●Provide education to the child and caregivers about the risks and complications of ITP and when to seek care. Information for patients and families/caregivers is provided below (see 'Information for patients' below). Additional resources include the National Institutes of Health website and the Platelet Disorder Support Association website.
●Some patients with chronic ITP may have considerable fatigue or symptoms of depression and anxiety. Other potential causes of fatigue should be investigated in these cases (eg, poor sleep habits, poor nutrition, iron deficiency, hypothyroidism). It is uncertain whether pharmacologic therapy for ITP improves fatigue or mood symptoms in patients with chronic ITP. Some patients may require antidepressant medication for management of depressed mood. (See "Overview of prevention and treatment for pediatric depression" and "Pharmacotherapy for anxiety disorders in children and adolescents".)
Many of these supportive interventions are discussed in greater detail separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'General measures'.)
Monitoring — The frequency of laboratory monitoring for patients with chronic ITP depends on clinical symptoms, severity of thrombocytopenia, stability of the platelet count, and the treatment being used. For example, if a previously asymptomatic patient develops new bleeding symptoms requiring treatment, weekly monitoring with a complete blood count (CBC) is often appropriate until the symptoms resolve and the platelet count stabilizes. If a patient has minimal symptoms and the CBC is stable at a moderate degree of thrombocytopenia (50,000 to 100,000/microL), monitoring can be done less frequently (eg, once a month to every four months).
In our practice, we usually stop monitoring after the platelet count has returned to normal and has remained stable for 6 to 12 months without treatment, though we may monitor it longer in patients who had longstanding ITP before entering remission.
Patients with chronic ITP also should be evaluated at least annually for thyroid disease because of the high association between ITP and autoimmune thyroid disease [15]. We also screen for common variable immunodeficiency with immunoglobulin levels and/or antibody response to routine childhood vaccines annually. In addition, in adolescent female patients with chronic ITP, we check antiphospholipid antibodies (aPL) and antinuclear antibody (ANA) levels annually since the prevalence of autoimmune disease is particularly high in this group. (See 'Ongoing evaluation' above and "Acquired hypothyroidism in childhood and adolescence", section on 'Autoimmune thyroiditis' and "Common variable immunodeficiency in children".)
MANAGEMENT APPROACH —
For patients with persistent or chronic ITP, platelet counts can vary considerably and thus the need for pharmacologic intervention varies:
●Some patients maintain platelet counts between 30,000 to 100,000/microL without treatment. Such patients generally do not experience bleeding symptoms and do not require additional treatment unless a higher platelet count is needed (eg, for surgery). (See 'Intervention prior to surgery' below.)
●Some patients remain relatively asymptomatic, but they may require occasional acute intervention for management of intermittent episodes of clinically significant thrombocytopenia, which may be triggered by an infection. For these patients, we generally use the same agent that the patient responded to in the past.
●Other patients may require continuous or intermittent therapy for management of ongoing or recurrent bleeding symptoms or risks. (See 'Patients requiring ongoing therapy' below.)
Children with persistent or chronic ITP should be managed by a pediatric hematologist whenever possible. If regular visits to the hematologist are challenging for the family (eg, if it requires long-distance travel back and forth to the specialty clinic), virtual visits using telehealth may be an option. The primary care provider should participate in the care and examinations and remain in close touch with the hematologist.
The following sections outline our suggested approach to managing pediatric patients with persistent or chronic ITP. Additional details on specific second-line agents, including dosing guidance, side effects, and efficacy are provided below. (See 'Second-line agents' below.)
First-line agents are summarized in the table (table 4) and discussed in detail separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'First-line treatments'.)
Acute intervention for bleeding episodes — The first-line pharmacologic options for acute intervention are similar to those used in the initial management of patients with newly diagnosed ITP and include intravenous immune globulin (IVIG), anti-D immune globulin (anti-D), or glucocorticoids alone or in combination (table 4). Platelet transfusions are generally reserved for episodes of severe bleeding, major trauma, or emergency surgery. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Treatment approach'.)
The dosing and administration of IVIG, anti-D, and glucocorticoids are the same as for initial management, as summarized in the table (table 4) and discussed separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'First-line treatments'.)
Antifibrinolytic agents (eg, tranexamic acid) and/or hormonal therapies may be useful in patients with severe epistaxis or heavy menstrual bleeding, as discussed below. (See 'Adjunctive therapies' below.)
Frequent or prolonged use of glucocorticoids (ie, more than two to four weeks) should be avoided in children because of well recognized adverse effects on growth, bone health, immune function, and vision [17]. (See "Major adverse effects of systemic glucocorticoids".)
Since there are other effective and safer treatments available, children requiring frequent or prolonged treatment should be managed with steroid-sparing agents (eg, IVIG, thrombopoietin receptor agonists [TPO-RAs]), or rituximab) [17]. Other agents that are sometimes used for ongoing treatment of chronic ITP include azathioprine, 6-mercaptopurine (6-MP), mycophenolate mofetil (MMF), sirolimus, or cyclosporine. (See 'Thrombopoietin receptor agonists' below and 'Rituximab' below and 'Other agents' below.)
Intervention prior to surgery — When an increased platelet count is needed for surgery or an invasive procedure, any first- or second-line ITP therapy may be used (glucocorticoids, IVIG, anti-D, TPO-RA, rituximab) (table 4). Considerations include the timing of surgery, the desired platelet count, the potential for bleeding during recovery after surgery, and the patient's prior treatment response.
For most children undergoing elective major procedures, we suggest treatment with a TPO-RA if there is sufficient time before surgery, because these agents are effective for raising and maintaining the platelet count for as long as they are continued. These agents have at least a five- to seven-day delay before a response is seen, so they are not appropriate if an increased platelet count is needed urgently.
By contrast, IVIG or a short course of glucocorticoid therapy will raise the platelet count in most patients, but the effect starts to wane after 3 to 10 days. If IVIG or glucocorticoids are used in this setting, treatment should be initiated one to three days prior to planned surgery unless the patient is known to have a delayed response to these agents. Starting therapy earlier (ie, more than five to seven days before surgery) may result in an initial rise in the platelet count followed by a drop in the platelet count coinciding with the time of surgery.
If there is insufficient time to effectively raise the platelet count with pharmacologic therapy or if the response to therapy is inadequate, surgery may have to be rescheduled.
Management of ITP in the setting of surgery and invasive procedures is discussed in greater detail separately. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Surgery/invasive procedures'.)
Ongoing management
Patients requiring ongoing therapy — For patients with persistent or chronic ITP whose symptoms and risks are not adequately controlled using first-line therapies (eg, those who would otherwise require frequent and/or prolonged glucocorticoid therapy to control symptoms), we suggest starting a second-line therapy.
However, decisions regarding when to initiate a second-line therapy should be individualized and made in collaboration with the patient and family/caregivers. The threshold for starting a second-line treatment depends on multiple factors, including:
●Burden of bleeding symptoms
●Quality of life
●Risk factors for bleeding (sports or an active lifestyle)
●Concomitant medical conditions and medications
●Patient and parent/caregiver anxiety
●Fatigue
●Access to medical care
In a prospective multicenter longitudinal cohort study of 120 children with ITP who were treated with second-line agents, the most frequently cited reasons for starting second-line therapy included severity or frequency of bleeding symptoms (34 percent), quality of life (27 percent), and severity of thrombocytopenia (15 percent) [18].
Choice of second-line therapy — Second-line treatment options include:
●TPO-RAs (eltrombopag, romiplostim) (see 'Thrombopoietin receptor agonists' below)
●Rituximab (see 'Rituximab' below)
●Other immunosuppressive agents (eg, azathioprine, 6-MP, MMF, sirolimus, cyclosporine, dapsone) (see 'Other agents' below)
●Splenectomy, which in the contemporary era is rarely used to treat ITP in children (see 'Splenectomy' below)
In our practice, we most commonly use TPO-RAs for patients with ITP lasting ≥3 to 6 months who require pharmacologic intervention (see 'Thrombopoietin receptor agonists' below). Exceptions include patients with autoimmune disorders or autoantibodies for whom we prefer rituximab since TPO-RAs do not have immunomodulatory effects (see 'Rituximab' below). Other immunosuppressive agents (eg, MMF, sirolimus) may also be considered in patients with autoimmune disorders, particularly in patients with ALPS. (See 'Other agents' below and "Autoimmune lymphoproliferative syndrome (ALPS): Management and prognosis".)
The author of this topic also prefers rituximab for treatment of chronic ITP in adolescent female patients since there is a high prevalence of underlying autoimmune disease in this population [19]. However, this is not standard practice, and other experts (including the section editor of this topic) prefer TPO-RAs for most adolescent female patients unless an autoimmune disorder has been definitively diagnosed.
Other considerations in the treatment choice include [20]:
●Ease of administration – Eltrombopag is administered orally and may be preferred by patients who wish to avoid intravenous infusions or subcutaneous injections. However, some patients find it difficult to adhere to the cumbersome dietary requirements for taking the drug as described below. (See 'Thrombopoietin receptor agonists' below.)
Oral immunosuppressive agents (eg, azathioprine, 6-MP, or MMF) are another option. However, the efficacy of these agents is less certain, and they are probably less effective than TPO-RAs. In addition, the response to these agents can be delayed, sometimes for months. Oral immunosuppressive agents all have potential for toxicity, though they are usually well tolerated when used as monotherapy. These and other issues should be carefully discussed with the patient and caregivers when selecting therapy. (See 'Other agents' below.)
●Expected adherence to treatment regimen – For patients with difficulty adhering to a medication regimen, rituximab may be preferred since it does not require day-to-day self-management once/if a durable response is seen. (See 'Rituximab' below.)
●Possibility of long-term remission – Most second-line agents do not achieve a durable response over time. Among the various choices for second-line therapy, splenectomy has the greatest likelihood of resulting in a sustained remission. However, splenectomy is associated with substantial risks, including thrombosis and lifelong risk of overwhelming sepsis. In addition, there is a greater tendency to spontaneous remission in children with ITP compared with adults such that the temporary response from pharmacologic therapy may be adequate to support the child until remission occurs spontaneously. Splenectomy plays a very limited role in the management of pediatric ITP in contemporary practice, as discussed below. (See 'Splenectomy' below.)
Poor response to second-line therapy — If the selected agent at maximal dose for four weeks is ineffective, we take the following steps:
●Reevaluate for other potential causes of chronic thrombocytopenia. (See 'Ongoing evaluation' above.)
●Change to another TPO-RA agent or add an immunosuppressive agent (eg, MMF). The mechanism by which TPO-RAs stimulate thrombopoiesis is different for each agent. Thus, lack of response to one TPO-RA does not mean that there will be no response to a different TPO-RA. (See 'Thrombopoietin receptor agonists' below.)
Chronic refractory ITP — Chronic refractory ITP (generally defined as chronic ITP without a lasting response to standard pharmacologic treatments) is rare in pediatric patients, and a standard approach to its evaluation and management is lacking. These patients should be managed by or in consultation with a pediatric hematologist experienced in treating refractory ITP. The general approach is as follows:
●Evaluation – It is increasingly recognized that many patients labeled as having chronic refractory ITP do not have primary ITP, but rather have another cause of chronic thrombocytopenia (eg, inherited thrombocytopenia syndrome, bone marrow failure or myelodysplastic syndrome, immunodeficiency, chronic infection) [21,22]. Thus, a thorough evaluation should be performed in patients with what appears to be chronic refractory ITP. There is no one-size-fits-all approach, and testing should be guided by the age, accompanying clinical findings, and initial evaluation. (See 'Ongoing evaluation' above.)
Evaluation for inherited thrombocytopenia (eg, with a selected gene panel) can often be useful. A list of laboratories performing testing for inherited platelet disorders is available on the Genetic Testing Registry. Gene panels are also available for immunodeficiency disorders and bone marrow failure syndromes. (See "Causes of thrombocytopenia in children", section on 'Inherited platelet disorders'.)
●Management – Agents that have been used for management of chronic refractory ITP in childhood include azathioprine, 6-mercaptopurine (6-MP), cyclosporine, dapsone, mycophenolate mofetil (MMF), and sirolimus. Additional agents that can be used after the child enters puberty include danazol, hydroxychloroquine, and cyclophosphamide. As discussed below, the use of these agents is based on anecdotal clinical experience in children and small clinical trials in adults. (See 'Other agents' below and "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Immunosuppressive agents'.)
Many truly refractory patients are not responsive to single agents, and, therefore, using drug combinations (especially agents with different mechanisms of effect and non-overlapping toxicities) is a useful strategy in this setting. Combination therapy may achieve at least a limited response using relatively low doses of individual agents, thereby potentially avoiding or minimizing toxicity. Specific combination regimens have not been well defined or established, but the regimen usually includes a TPO-RA agent plus one or two other agents (eg, azathioprine, MMF, rituximab, or cyclosporin). There are scant data on use of combination therapy in pediatric patients with chronic refractory ITP. Studies in adult patients are discussed separately. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Combinations'.)
Fostamatinib, an inhibitor of Syk (spleen tyrosine kinase), is an agent that is approved for treatment of adults with chronic refractory ITP. It is not approved for use in pediatric patients. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Fostamatinib'.)
SECOND-LINE AGENTS —
The following sections summarize second-line agents that are used to treat persistent and chronic ITP in pediatric patients. The choice between these agents is outlined above. (See 'Choice of second-line therapy' above.)
Thrombopoietin receptor agonists — TPO-RAs (eg, eltrombopag, romiplostim) have emerged as effective agents for treatment of children with persistent and chronic ITP. TPO-RAs are our preferred agents for most children requiring second-line therapy.
TPO-RAs stimulate thrombopoiesis via the thrombopoietin receptor and are commonly used for second-line treatment in adult patients with chronic ITP. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO receptor agonists'.)
TPO-RAs only support an increased platelet count as long as they are continued. However, since there is a greater tendency to spontaneous remission in children with ITP compared with adults, a temporary response may be adequate to support the child until remission occurs spontaneously. It has been theorized that chronic use of TPO-RAs could induce regulatory T cells, which may promote remission; however, this has not been demonstrated in clinical studies.
The routine use of these agents may be limited by cost considerations.
Dosing and administration — Available TPO-RAs for use in children include eltrombopag and romiplostim. Eltrombopag is given orally once daily, and romiplostim is administered once weekly via subcutaneous injection. Both agents are approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in pediatric patients ≥1 year old with chronic ITP refractory to other treatments [23-25]. A third agent, avatrombopag, which is a once daily oral agent without dietary restrictions, is approved for use in adult patients; it is being investigated in pediatric patients [26].
TPO-RAs are titrated to keep the platelet count in a safe range (typically, ≥50,000/microL) without causing thrombocytosis. Dosing starts with a low initial dose that is adjusted as needed, with close monitoring of the platelet count until a stable dose is reached. (See 'Monitoring' below.)
●Eltrombopag – The initial dose of eltrombopag is based on the age of the child [27]:
•Children 1 to 5 years – Initial dose is 25 mg orally once daily
•Children ≥6 years – Initial dose is 50 mg orally once daily
Dose reductions are necessary for patients with hepatic impairment and some patients of Eastern Asian ancestry (the latter applies only to children ≥6 years old).
Eltrombopag must be taken on an empty stomach without any intake within two hours before or after and without dairy (high calcium or iron intake) for four hours before or after. This may be prohibitive for some children, especially young children.
The dose is adjusted in increments of 12.5 mg every two weeks (maximum dose 75 mg per day) as necessary according to the response.
Some children may require high doses. For example, in the clinical trial described below, many patients, particularly young children, required doses >2 to 3 mg/kg [27]. This is considerably higher than the adult per kg dose (which is approximately 1 mg/kg). This likely reflects accelerated metabolism and/or lesser sensitivity of marrow precursors to eltrombopag in children compared with adults.
●Romiplostim – We typically start romiplostim at a dose of 3 mcg/kg per dose given subcutaneously once weekly, though a lower starting dose (1 mcg/kg) is suggested by the manufacturer. The dose is then adjusted in increments of 1 mcg/kg per week (maximum dose 10 mcg/kg per week) as needed according to the response.
In one study of >200 children with ITP lasting ≥6 months who were treated with romiplostim for a median duration of three years, the average weekly dose was 6.9 mcg/kg [28].
Monitoring
●Platelet count monitoring – For children who respond to TPO-RAs, the platelet count usually increases in approximately 7 to 14 days.
To avoid risks of thrombocytosis, we generally check the platelet count:
•At five to seven days after starting therapy
•One week after dose changes
•Monthly once a stable dose is reached
•Any time there is a new clinical concern for worsening thrombocytopenia (eg, petechiae, mucosal bleeding, intercurrent illness)
●Other monitoring – For eltrombopag, liver enzymes should be measured prior to drug initiation, every two weeks during dose adjustments, and monthly thereafter.
Adverse effects — The available data suggest that eltrombopag and romiplostim are generally safe and well tolerated in adults and children. In clinical trials, headache and mild gastrointestinal (GI) complaints were the most commonly reported side effects.
Serious adverse events are rare and may include:
●Thrombosis – TPO-RAs may increase the risk of thrombosis in patients with underlying risk factors for thrombosis, but these issues are far less common in children than in adults. In a multicenter retrospective study of 79 children treated with TPO-RAs, pulmonary embolism (PE) occurred in two patients (2.5 percent) [29]. Both patients had other underlying risk factors for thrombosis, and neither had thrombocytosis at the time the PE developed.
●Hepatotoxicity (eltrombopag only) – Eltrombopag can cause transaminitis, which is usually mild and reversible [27,29]. In the clinical trial described below (PETIT2), 3 percent of treated patients had to discontinue eltrombopag because of transaminitis [27]. All patients receiving eltrombopag should have routine monitoring of liver enzymes. (See 'Monitoring' above.)
●Cataracts – It is unclear if TPO-RAs increase the risk of cataract. There have been a few reports of cataracts occurring in patients treated with eltrombopag [27,29]. However, many patients undergoing treatment for chronic ITP have been chronically exposed to glucocorticoids, which can also cause or contribute to cataract development. We do not routinely perform eye examinations if eltrombopag is used, but we do ask about vision changes. In the PETIT2 trial, two patients treated with eltrombopag (3 percent) developed new or worsening cataracts; both were receiving glucocorticoids [27]. However, in a longitudinal cohort study of 116 children receiving eltrombopag, no patients had newly diagnosed cataracts [30].
●Antibody formation (romiplostim only) – Up to 3 percent of children treated with romiplostim develop antibodies [28]. However, most of these antibodies have little to no effect on the platelet count.
As eltrombopag is a non-peptide agent, it does not carry a risk of antibody formation. (See "Clinical applications of thrombopoietic growth factors", section on 'Antibody formation'.)
●Bone marrow fibrosis – Initial concerns were raised regarding the possibility of increasing bone marrow reticulin formation with romiplostim and eltrombopag; however, this was not confirmed in follow-up studies [31]. (See "Clinical applications of thrombopoietic growth factors", section on 'Bone marrow fibrosis'.)
Additional details on adverse effects of TPO-RAs are provided separately. (See "Clinical applications of thrombopoietic growth factors", section on 'Side effects and risks'.)
Efficacy — The efficacy of eltrombopag and romiplostim for treatment of persistent and chronic ITP in pediatric patients is supported by placebo-controlled trials and observational studies [27,29,30,32-37]. Based on the available evidence, both agents appear to have comparable efficacy, though there are no trials directly comparing the two agents [29,33,34,36-40].
●Eltrombopag – The efficacy and safety of eltrombopag in children with persistent or chronic ITP were investigated in two placebo-controlled trials, PETIT and PETIT2, which were the basis for the drug's regulatory approvals for use in children [27,32]. In a meta-analysis of both trials, bleeding episodes occurred less frequently in eltrombopag-treated patients compared with placebo (34 versus 67 percent; relative risk [RR] 0.50, 95% CI 0.29-0.87) [41]. Most bleeding episodes were mild to moderate; no patient in either treatment group experienced serious or life-threatening bleeding. Patients in the eltrombopag group were more likely to have a rise in their platelet count to ≥50,000/L compared with those in the placebo group (49 percent versus 16 percent); however, the difference was not statistically significant (RR 3.93, 95% CI 0.56-27.8). Rescue medications were used less commonly in the eltrombopag group (17 versus 35 percent).
In the larger of two trials (PETIT2; n = 92 patients), a durable platelet response (defined as platelet count ≥50,000/microL for six of eight weeks during the double-blind period) occurred more frequently with eltrombopag therapy than with placebo (40 versus 3 percent, respectively) [27]. During the 24-week open-label treatment period that followed the randomized trial, 81 percent of patients achieved at least one platelet count >50,000/microL. (See 'Adverse effects' above.)
Data on long-term use of eltrombopag in children remain limited. The experience using eltrombopag in the "real-world" setting (ie, outside of a clinical trial) has been described in a few reports which generally confirm the efficacy reported in the trials, with 60 to 75 percent of patients demonstrating a response to treatment [30,35]. In these studies, most patients using concomitant ITP medications at the time of starting eltrombopag were able to reduce or discontinue other medications after 6 to 12 months of eltrombopag therapy.
●Romiplostim – The efficacy and safety of romiplostim in children were investigated in three small randomized trials involving a total of 112 children with persistent or chronic ITP [33,34,42]. In a meta-analysis of all three trials, the response rate (defined as rise in the platelet count to ≥50,000/L) was higher in romiplostim-treated patients compared with placebo (68 versus 2 percent; RR 6.8, 95% CI 2.3-20.3) [41]. Bleeding episodes (most of which were minor) occurred at similar rates in both groups (44 and 46 percent). Rescue medications were used less commonly in the romiplostim group (7 versus 15 percent).
Long-term use of romiplostim in children suggests that platelet counts can be maintained for over four years with good tolerability and without major toxicity similar to long-term data reported in adults [36]. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'TPO-RAs efficacy and adverse events'.)
In one study of >200 children with ITP lasting ≥6 months who were treated with romiplostim for a median duration of three years, 88 percent had a platelet response (ie, rise in platelet count to >50,000/microL) at some time during treatment [28]. During the first six months of therapy, 50 percent of measured platelet levels were in acceptable range (ie, >50,000/microL); this rose to 78 percent by the end of the three-year treatment period. Moderate or greater bleeding episodes (ie, grade 3 or higher on the on the modified Buchanan and Adix bleeding score (table 5)) occurred in 10 percent of patients, mostly during the first six months of therapy. Treatment was discontinued in 47 percent of patients. Reasons for discontinuation included lack of efficacy (21 percent), patient request/inability to comply with treatment (10 percent), adverse events (4 percent), and development of neutralizing antibodies (3 percent).
Lack of response over time due to neutralizing antibodies has been reported and appears to be more common in children compared with adults [29]. (See 'Adverse effects' above.)
●Variability in the response over time – In the clinical trials discussed above, most patients had a sustained response to eltrombopag or romiplostim; however, on-treatment platelet counts can fluctuate considerably over time. In a multicenter retrospective study of 79 children treated with TPO-RAs (43 with romiplostim, 28 treated with eltrombopag, and 8 with both agents), only 40 percent of patients maintained a stable response with consistent dosing over time [29]. An intermittent response requiring constant dose titration was seen in 15 percent, and an initial response that waned to no response was seen in 13 percent. In one child, the lack of response was explained by the presence of a neutralizing antibody to romiplostim (see 'Adverse effects' above). In other cases, the cause for the waxing and waning response when it occurs is uncertain. Poor response to eltrombopag in particular may be due to difficulties adhering to the strict dietary requirements for taking the drug.
Rituximab — Rituximab is a chimeric murine/human anti-CD20 monoclonal antibody that targets autoantibody-producing B lymphocytes but not plasma cells [43,44]. Several uncontrolled observational studies support its use in pediatric patients with persistent or chronic ITP [19,45,46]. Randomized controlled trial data in pediatric patients are lacking. Indirect evidence comes from clinical trials in adults with ITP, which are discussed separately. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Rituximab'.)
●Dosing and administration – Optimal dosing for rituximab in pediatric patients is not defined. The typical dose is 375 mg/m2 intravenously weekly for four weeks [44,47]. Higher doses (eg, 1000 mg as a flat dose) and lower doses have also been used.
We suggest premedication with a single dose of methylprednisolone prior to the first infusion to minimize acute infusion reactions, especially fever and chills.
A preparation of rituximab for subcutaneous injection is also available. Biosimilars and second generation anti-CD20 monoclonal antibody agents have been developed and used in the treatment of other conditions (lymphoma, chronic lymphocytic leukemia), but have not been studied in children with ITP [48].
●Efficacy – Observational studies in children with chronic ITP suggest an initial response rate of approximately 40 to 50 percent, falling to approximately 25 percent over follow-up of two to five years [45,46]. In a retrospective study of 33 children with chronic ITP who were treated with four infusions of rituximab, 30 percent maintained a response at 60 months [19]. The response rate in adolescent females (50 percent) was higher than in younger children and males.
●Adverse effects – Adverse effects of rituximab include infusion reactions and prolonged immunosuppression. Mild, transient side effects may occur with the first infusion, including urticarial rash, headache, fever, scratchy throat, and chills. This may mimic an allergic response but is due to the B cells present in Waldeyer's ring. These side effects are less common with subsequent infusions because there are generally very few circulating B cells.
Serum sickness occurs in 5 to 10 percent of children with ITP treated with rituximab, a rate that is higher than in adults [44,46].
Severe hypogammaglobulinemia is infrequent with rituximab alone; however, it can occur if rituximab is administered concomitantly with dexamethasone. It is occasionally severe enough to require replacement [49]. Infrequently, B cell reconstitution may be delayed or incomplete following rituximab treatment [50]. (See "Secondary immunodeficiency induced by biologic therapies".)
Progressive multifocal leukoencephalopathy (PML) has been reported as a very rare but serious complication [51].
●Pretreatment testing and precautions – Pretreatment testing includes (see "Secondary immunodeficiency induced by biologic therapies"):
•Patients should be screened for hepatitis B virus (HBV) infection before starting rituximab because of the risk of HBV reactivation. Rituximab is generally avoided in individuals with active or occult HBV infection. (See "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents", section on 'Screening'.)
•Serum immunoglobulin levels (total, IgG, IgM, and IgA).
•Treatment with rituximab can suppress vaccine responses for at least six months after administration. Thus, appropriate polysaccharide vaccines and primary non-live immunizations should be administered prior to starting rituximab therapy. Live vaccines (eg, measles-mumps-rubella or varicella zoster virus) should not be given in close proximity to rituximab; these should be deferred for at least six months after the end of treatment. (See "Secondary immunodeficiency induced by biologic therapies".)
Other agents — Additional immunosuppressive agents are frequently used in children with late persistent or chronic ITP. These include:
●Danazol (after the child has entered puberty) [53]
●6-MP [61]
●MMF [62,63]
The most widely used agents are MMF, 6-MP, cyclosporine, and dapsone (the latter predominantly outside of the United States). Sirolimus and hydroxychloroquine are also used in specific circumstances (sirolimus for patients with autoimmune lymphoproliferative syndrome or Evans syndrome; hydroxychloroquine for patients with positive antinuclear antibodies and/or systemic lupus erythematosus).
The use of these agents in childhood ITP is based on anecdotal clinical experience and small clinical trials in adults. None of these agents have been demonstrated to have unequivocal curative effects and all have some toxicity (hepatotoxicity, increased risk of infection). Response rates to these agents are generally low. Nonetheless, these agents may have utility in chronic cases of ITP, alone or in combination with other agents. Combining immunosuppressive agents may increase efficacy but may also increase toxicity, especially the risk of infections [65]. A strategy to reduce the risk of toxicity when using combination therapy is to select agents with different mechanisms and side effect profiles and use relatively low doses of each individual agent.
SPLENECTOMY —
In the contemporary era, splenectomy is very rarely performed in the management of pediatric ITP. It is an option for the small subset of patients with chronic ITP who have persistent clinically significant, generally severe thrombocytopenia accompanied by hemorrhagic symptoms and require repeated or continuous pharmacologic interventions. Although splenectomy is effective in most patients, it is associated with substantial risks (eg, overwhelming sepsis and thrombosis). These risks are lifelong and therefore are greater in children compared with adults. Rates of splenectomy among children with ITP have declined considerably since the early 2000s, likely due to greater awareness of the risks of splenectomy, increased availability of other effective second-line therapies, and a shift in practice towards less aggressive treatment for children with ITP [66]. (See 'Choice of second-line therapy' above.)
●Efficacy – Based upon observational data, splenectomy is effective (ie, it improves the platelet count and reduces the associated risk of bleeding) in approximately 60 to 80 percent of children with chronic ITP [67].
●Risks – Splenectomy is associated with important risks, which must be weighed against the benefits. The most critical is the small but lifelong risk of overwhelming infection, which occurs in approximately 1 to 3 percent of splenectomized patients, usually with encapsulated organisms such as Pneumococcus, Haemophilus, and Neisseria. This risk is highest in young patients (<5 years old) and those with underlying immune dysfunctions (eg, ALPS) [68]. (See "Autoimmune lymphoproliferative syndrome (ALPS): Management and prognosis", section on 'Avoidance of splenectomy'.)
The other major long-term risk associated with splenectomy is thrombosis, particularly stroke. In a population-based study, patients who underwent splenectomy (mostly adults) had a 1.5-fold increased risk of stroke compared with nonsplenectomized patients [69]. In addition, pulmonary hypertension has been observed in splenectomized patients with hereditary spherocytosis, though this is not well studied in patients with ITP. (See "Hereditary spherocytosis", section on 'Splenectomy'.)
●Evaluation prior to splenectomy – Prior to planned splenectomy, the diagnosis of ITP should be critically reviewed to exclude causes of thrombocytopenia other than ITP, especially those related to immune deficiency, ongoing viral infection, systemic autoimmune disease (eg, systemic lupus erythematosus), bone marrow failure, or an inherited form of thrombocytopenia (table 3). This includes a comprehensive serologic evaluation, as previously described (see 'Ongoing evaluation' above), as well as additional testing (eg, bone marrow examination, imaging studies).
In addition, in our practice, in the rare instance when splenectomy is being considered in a child with ITP, we perform a bone marrow examination prior to the procedure unless there is a documented recent and robust response to IVIG or another ITP therapy demonstrating that the bone marrow is intact. Our practice differs somewhat from the 2011 American Society of Hematology (ASH) guidelines, which state that splenectomy is not necessarily an indication for bone marrow biopsy [70]. This guidance was not revisited in the 2019 ASH guidelines [17].
●Immunizations and infection prevention – Presplenectomy immunizations are necessary, and subsequent penicillin prophylaxis may be appropriate depending on the child’s age and other considerations. These issues are discussed in detail in a separate topic review. (See "Prevention of infection in patients with impaired splenic function".)
●Monitoring after splenectomy – Platelet counts should be monitored for an indefinite period following splenectomy until the count is clearly stabilized without additional treatment. Once stabilized, the platelet count should be monitored yearly if the count has returned to normal or more frequently if the count remains low. Pneumococcal titers can be measured yearly to determine if additional vaccination is warranted, though consensus is lacking as to the optimal frequency of revaccination. (See "Prevention of infection in patients with impaired splenic function", section on 'Vaccinations'.)
Patients who initially responded to splenectomy but then relapsed in the first two years postsplenectomy should be evaluated for the possibility of an accessory spleen.
ADJUNCTIVE THERAPIES —
Adjunctive therapies may be used in the following settings to treat or reduce the likelihood of clinically significant bleeding:
●Therapies to address heavy menstrual bleeding – In patients with heavy menstrual bleeding, hormonal therapy may be helpful to reduce bleeding. We generally use progesterone-only therapy or a low-estrogen formulation rather than a standard estrogen-based contraceptive. This is because limited data suggest that progesterone may have positive effects on platelet counts in ITP [71], while estrogen may promulgate autoimmunity and worsen the ITP [72]. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Progestin-only therapies'.)
Antifibrinolytic agents (eg, epsilon aminocaproic acid or tranexamic acid) can also be used to treat heavy menstrual bleeding, as discussed for mouth and nose bleeding below.
●Therapies for mouth and nose bleeding – Antifibrinolytic agents (eg, tranexamic acid) can be used in children with significant mucosal bleeding, including oral bleeding and epistaxis. Antifibrinolytic agents may also be used instead of or in addition to measures to raise the platelet count prior to dental work. Intranasal DDAVP (desmopressin) is another option for children with nose bleeding. Additional measures for nose bleeding include keeping the nasal mucosa moist (eg, with a humidifier or saline nose spray), discouraging nose picking, and use of antiallergy remedies (if allergic rhinitis is thought to be contributing). Ointments that require direct application are generally not helpful since the benefit of the ointment is offset by the trauma of the application. Cautery may be useful if a large vessel is visualized but is rarely effective if used for a second time in the same nostril and may damage the mucosa, paradoxically resulting in more bleeding. (See "Management of epistaxis in children".)
●Iron therapy for patients with significant bleeding – Patients who have recurrent significant bleeding symptoms, including adolescent females with heavy menses, should be evaluated for iron deficiency, and iron supplementation should be provided if warranted. (See "Iron requirements and iron deficiency in adolescents".)
PROGNOSIS
Spontaneous remission — Spontaneous remission occurs in up to half of children with chronic ITP, though it can take months to several years. In two large registry studies, approximately 25 to 35 percent of children with chronic ITP had complete remission over follow-up of one to two years [6,7]. At five years, approximately 50 percent had recovered completely, while 12 percent of patients had platelet counts <20,000/microL [6].
Remission is more likely in younger children (<10 years old) and if the platelet count is not very low [73,74]. Children >10 years old, especially adolescent females, have a disease course more like that seen in adults with ITP. Neither of these tendencies is enough to substantially alter management. The role that hormonal and other physiologic changes of puberty play in this process is not well understood. (See "Initial treatment of immune thrombocytopenia (ITP) in adults", section on 'Disease course'.)
Bleeding risk — The risk of serious bleeding in chronic ITP is modest and depends largely upon the platelet count. A very low count is permissive, but not sufficient, for severe bleeding to occur. In one large registry study, 8 percent of patients with chronic ITP experienced a serious bleeding episode over five years of follow-up [6]. In each case, the bleeding episode was in the context of a platelet count <20,000/microL. Patients with very low platelet counts (eg, <10,000/microL) are at risk for serious bleeding even if they have not had previous bleeding. However, there is individual variation in bleeding severity, which is not well understood and is independent of the platelet count. This may be explained by differences in endothelial and platelet function that are difficult to capture with available tests.
Intracranial hemorrhage is very rare (<1 percent), but the risk may be slightly higher among patients with chronic ITP as compared with those with newly diagnosed ITP [75]. Nearly all cases of intracranial hemorrhage occur at platelet counts <10,000/microL. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Intracranial hemorrhage'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immune thrombocytopenia (ITP) and other platelet disorders".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Immune thrombocytopenia (ITP) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition – Immune thrombocytopenia (ITP) is an immune-mediated process causing low platelet count (<100,000/microL) without other hematologic abnormalities. Persistent ITP is defined as ongoing ITP between 3 and 12 months from initial diagnosis and chronic ITP is defined as ITP persisting beyond 12 months from the initial presentation. Approximately 10 to 20 percent of children with ITP develop chronic ITP. Risk factors for chronic ITP include adolescent age, less severe thrombocytopenia and/or bleeding symptoms at the initial diagnosis, insidious onset of symptoms, and underlying chronic medical conditions (eg, autoimmune disorders, immunodeficiency). (See 'Terminology' above and 'Risk factors for chronic ITP' above.)
●Additional evaluation – Children who develop persistent or chronic ITP should have an additional evaluation both to exclude other causes of persistent thrombocytopenia (eg, bone marrow failure, inherited thrombocytopenia) (table 3) and to assess for underlying or secondary causes of ITP such as immunodeficiency, chronic infection, or systemic autoimmune/inflammatory disorders. (See 'Ongoing evaluation' above.)
●General measures – Supportive care for children with persistent or chronic ITP typically involves the following (see 'Supportive care' above and "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'General measures'):
•Restricting physical activities (eg, avoiding high-contact sports); however, it is important to not overly restrict participation in sports or social activities
•Avoiding medications with antiplatelet activity (especially nonsteroidal anti-inflammatory drugs)
•Regular laboratory monitoring
•Monitoring and/or treatment for heavy menstrual bleeding, epistaxis, and other bleeding symptoms
●Acute intervention for severe bleeding – The first-line pharmacologic options for acute intervention are similar to those used in the management of patients with newly diagnosed ITP and include intravenous immune globulin (IVIG), anti-D immune globulin (anti-D), or glucocorticoids alone or in combination (table 4). Platelet transfusions are generally reserved for episodes of severe bleeding, major trauma, or emergency surgery. (See "Immune thrombocytopenia (ITP) in children: Management of newly diagnosed patients", section on 'Treatment approach'.)
Antifibrinolytic agents (eg, tranexamic acid) and/or hormonal therapies may be useful in patients with severe epistaxis or heavy menstrual bleeding. (See 'Adjunctive therapies' above and "Management of epistaxis in children" and "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Progestin-only therapies'.)
●Intervention prior to surgery – When an increased platelet count is needed for surgery or an invasive procedure, the choice of therapy is based upon the timing of surgery, the desired platelet count, the potential for bleeding during recovery after surgery, and the patient's prior treatment response. For most children undergoing elective major procedures, we suggest treatment with a thrombopoietin receptor agonist (TPO-RA) rather than other agents (Grade 2C), provided there is sufficient time before surgery. TPO-RAs have at least a five- to seven-day delay before a response is seen, so they are not appropriate if an urgent increase in platelet count is needed. (See 'Intervention prior to surgery' above.)
●Patients who require ongoing therapy – Prolonged daily use of glucocorticoids (more than two to four weeks) should be avoided because of the potential for adverse effects on growth, bone health, immune function, and vision. (See "Major adverse effects of systemic glucocorticoids".)
•Choice of second-line therapy – For most patients with persistent or chronic ITP whose symptoms and risks are not adequately controlled using first-line therapies (eg, those who would otherwise require frequent and/or prolonged glucocorticoid therapy to control symptoms), we suggest a TPO-RA agent (eltrombopag or romiplostim) rather than rituximab, other immunosuppressive drugs, or splenectomy (Grade 2C). Exceptions include patients with autoimmune disorders or autoantibodies, for whom we suggest rituximab (Grade 2C). (See 'Choice of second-line therapy' above and 'Second-line agents' above.)
While splenectomy is an effective alternative, it carries serious life-long risks (overwhelming infections, thrombosis) and is rarely performed to treat pediatric ITP in the contemporary era. (See 'Splenectomy' above.)
•Poor response to second-line therapy – If the selected agent at maximal dose for four weeks is ineffective, options include changing to a different TPO-RA agent (if applicable) or adding an oral immunosuppressive agent (eg, mycophenolate mofetil [MMF], 6-mercaptopurine [6-MP], azathioprine). In addition, patients with poor response to second-line therapies should be reevaluated for other causes of thrombocytopenia. (See 'Poor response to second-line therapy' above and 'Ongoing evaluation' above.)
●Prognosis – Approximately 30 percent of children with chronic ITP have spontaneous remission within two years in and approximately 50 percent have remission by five years. Spontaneous remission is more common in younger children and if the platelet count is not very low. Severe bleeding occurs in <10 percent of affected children over five-year follow-up. (See 'Prognosis' above.)
