Immune Thrombocytopenia (ITP) Treatment & Management

Updated: Mar 13, 2023
  • Author: Craig M Kessler, MD, MACP; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
  • Print

Medical Care

The goal of medical care for immune thrombocytopenia (ITP) is to increase the platelet count to a safe level, permitting patients to live normal lives while awaiting spontaneous or treatment-induced remission. ITP has no cure, and relapses may occur years after seemingly successful medical or surgical management. [6]

The treatment paradigm is shifting, with expanding experience with earlier use of thrombopoietin receptor analogs (TPO-RA; TPO-mimetics) in chronic ITP. However, this is not yet the standard of care. These agents may not be conducive to preventing or reversing the potential for acute bleeding complications in newly diagnosed ITP, given the delayed platelet count responses they produce. However, data are maturing on their use and long-term effectiveness.

Corticosteroids (ie, oral prednisone or high-dose dexamethasone) [9, 10, 11] remain the drugs of choice for the initial management of acute ITP, especially in the setting of life-threatening thrombocytopenia or when response in the platelet count is needed in an urgent or emergent setting. Treatment with corticosteroids may not only reduce the rate of platelet destruction but may also rapidly alter endothelial cell integrity to facilitate primary hemostasis and to reduce bleeding and bruising.

Because corticosteroid administration may change marrow morphology, performance of a bone marrow aspiration and biopsy should be considered to confirm the diagnosis of ITP if the clinical presentation, patient age, or other findings are atypical for acute ITP before the patient is treated with corticosteroids.

TPO-RA and rituximab are second-line options for patients with ITP lasting 3 months or more and in those who are corticosteroid dependent or have no response to corticosteroids. For adults who have had ITP for longer than 12 months, splenectomy is also a second-line option. In studies from Asia—principally, China—cyclosporine has demonstrated efficacy and safety as second-line treatment for ITP in adults and children, typically as part of combination therapy. [57]

Intravenous immunoglobulin (IVIG) can be the drug of second choice (after corticosteroids) for some patients, such as when a rapid increase in platelet count is important. [12, 13] However, for Rh(D)-positive patients with ITP and intact spleens, IV Rho immunoglobulin (RhIG) offers comparable efficacy, less toxicity, greater ease of administration, and a lower cost than IVIG. [14, 15]

The limitation of using IV RhIG is the lack of efficacy in Rh(D)-negative or splenectomized patients. Also, IV RhIG may induce immune hemolysis (immune hemolytic anemia) in Rh(D)-positive persons, which is the most common adverse effect, and should not be used when the hemoglobin concentration is less than 8 g/dL. Sporadic cases of massive intravascular hemolysis [16] disseminated intravascular coagulation (particularly in elderly individuals), and renal failure [17] have been reported.

Treatment in children

Most children with acute ITP do not require treatment, and thrombocytopenia resolves spontaneously. [7] American Society of Hematology (ASH) guidelines recommend that children who have no bleeding or minor bleeding (eg, cutaneous manifestations such as bruising and petechiae) be managed with observation alone regardless of platelet count. [8] A retrospective review by Schultz et al found that this approach did not lead to an increase in later treatment or an increase in delayed bleeding. [58]

For pediatric patients requiring treatment, ASH suggests a short course of corticosteroids for first-line treatment rather than IVIG or anti-D immunoglobulin. [8]

The ASH guidelines acknowledge the risk of hemolysis with IV RhoD immune globulin (RhIG, anti-D immune) and the black box warning related to fatal intravascular hemolysis, but notes these are rare events. [8]  An advantage of IV RhIG is that if bone marrow aspiration is unacceptable to parents and if the diagnosis of acute ITP is equivocal, IV RhIG is an effective treatment that avoids the problem of a misdiagnosis of acute leukemia because of steroid-related changes in the marrow.

For children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIG, RhIG, or conventional doses of corticosteroids, ASH suggests a TPO-RA rather than rituximab or splenectomy as second-line treatment. Rituximab may also be considered as an alternative to splenectomy. [8]

Treatment in adults

In adults, treatment is recommended for a platelet count < 30×109/L. The ASH recommends that if treatment is needed, shorter courses of corticosteroids (≤6 weeks) are preferred over prolonged courses (> 6 weeks including treatment and taper) as first-line treatment. The guidelines suggest either prednisone (0.5-2.0 mg/kg per day) or dexamethasone (40 mg per day for 4 days) as the type of corticosteroid for initial therapy.  [8]

In adults with ITP lasting ≥3 months who are corticosteroid-dependent or have no response to corticosteroids, the ASH guidelines suggest either splenectomy or a TPO-RA. In adults who are going to be treated with aTPO-RA, either eltrombopag or romiplostim is suggested by the ASH guidelines. ASH also suggests rituximab over splenectomy. [8]

Gudbrandsdottir et al reported that treatment with the combination of dexamethasone and rituximab resulted in higher response rates than with dexamethasone monotherapy (58%, versus 37% with dexamethasone alone; P = 0.02), as well as longer time to relapse (P = 0.03) and longer time to rescue treatment (P = 0.007). However, the incidence of grade 3 to 4 adverse events was higher in the rituximab plus dexamethasone group (P = 0.04). The study included 113 adult patients with newly diagnosed, symptomatic primary ITP. [59]

Additional precautions are required for patients with hypertension, peptic ulcers, recent aspirin ingestion, or other risk factors for increased bleeding. Considerations are as follows:

  • Aspirin inhibits platelet function by acetylating platelet cyclooxygenase, increasing the risk of bleeding because it adds a prolonged platelet functional defect to the quantitative defect already present from the severe thrombocytopenia. In addition, platelet dysfunction may be induced by the platelet antibody, which is potentiated by the superimposition of the aspirin-platelet defect. Because of this effect, aspirin is contraindicated in persons with ITP.

  • Adults whose platelet counts are greater than 50× 109/L typically have minimal purpura, and the risk of a severe or life-threatening hemorrhage is low. They may be treated without a specific medication.

  • Platelet transfusions may be required to control clinically significant or catastrophic bleeding but are not recommended for prophylaxis. Transfused platelets have decreased circulation time, and repeated platelet transfusions may lead to platelet alloimmunization.


Fostamatinib (Tavalisse) was approved by the US Food and Drug Administration (FDA) in 2018 for thrombocytopenia in adults with chronic ITP who have had an insufficient response to a previous treatment. It is the first spleen tyrosine kinase (SYK) inhibitor approved in the US. Approval was based on the FIT clinical program (n=163), which included 2 randomized placebo-controlled phase III trials and an open-label extension trial. [60]

In those randomized trials, more patients experienced a platelet response with fostamatinib than with placebo (18% vs 0% and 16% vs 4%). In the open-label expansion trial, 23% of patients who had received placebo in the previous randomized trials experienced a platelet response. Fewer bleeding episodes were observed in patients in the fostamatinib arm compared with placebo (29% vs 37%). Most of the patients who responded demonstrated durable platelet increments. [60]

Treatment in pregnant women

Pregnant women with no bleeding manifestations whose platelet counts are  30 × 109/L or higher do not require any treatment until 36 weeks' gestation, unless delivery is imminent. For pregnant women with platelet counts below 30 × 109/L, or clinically relevant bleeding, first-line therapy is oral corticosteroids or IVIG. Oral prednisone and prednisolone cross the placenta less readily than dexamethasone. Although ASH guidelines recommend a starting dose of prednisone of 1 mg/kg daily, other experts recommend a starting dose of 0.25 to 0.5 mg/kg, as there is no evidence that a higher starting dose is better. The recommended starting dose of IVIG is 1 g/kg. [18]

Refractory ITP in pregnancy can be treated with corticosteroids and IVIG in combination, or splenectomy (in the second trimester). [18] Rarely, splenectomy may be required to manage acute hemorrhage. [19]  

Azathioprine and RhIG are relatively contraindicated in pregnancy. The standard dose of IV RhIG for ITP contains approximately 10-fold the concentration of anti-D that is in the standard antepartum dose of intramuscular RhIG for Rh immunoprophylaxis. Other third-line agents that are not recommended in pregnancy, but whose use in this setting has been described, include the following agents (all of them pregnancy category C) [18] :

  • Cyclosporine
  • Dapsone
  • Thrombopoietin receptor agonists
  • Alemtuzumab
  • Rituximab

For more information, see Immune Thrombocytopenia and Pregnancy.

Thrombopoietin receptor agonists

For many years, the only treatment options after corticosteroids, IV RhIG, IVIG, and rituximab were cyclophosphamide, azathioprine, and danazol. Interventions with decreased certain efficacy and with conflicting reports in the literature include alemtuzumab, azathioprine, danazol, dapsone, vinblastine, vincristine, ascorbic acid, colchicine, and interferon alfa. [61, 62, 63, 64, 65, 66, 67]  In the past decade, thrombopoietin (TPO) receptor agonists have entered clinical practice as second-line agents. Three of these agents are currently available: romiplostin (Nplate), eltrombopag (Promacta), and avatrombopag (Doptelet).


The TPO receptor agonist romiplostim became available for patients with chronic ITP in 2008. Romiplostinm is administered weekly via subcutaneous injection and increases platelet counts within 5 to 8 days, with levels returning to baseline after 28 days. 

In one prospective, randomized controlled study comparing romiplostin with the standard of care for the treatment of chronic ITP, romiplostim administration was associated with higher rates of platelet count responses, decreased need for splenectomy, fewer episodes of serious bleeding and blood transfusions, and decreased need for initiating additional medical treatments. Romiplostim therapy was also associated with improved quality of life. [68] In a study of long-term romiplostim treatment, a small cohort of children with severe chronic ITP increased and maintained platelet counts for over 4 years, with good tolerability and without significant toxicity. [69]

In a phase III double-blind study of 62 symptomatic children with persistent or chronic ITP who were randomly assigned to receive weekly romiplostim or placebo for 24 weeks, durable platelet response was seen in 52% of patients receiving romiplostim vs.10% of those in the placebo group (p=0.002,906582 odds ratio 9.1). However, further studies are needed to determine long-term efficacy, safety, and remission rates. [70]  

A systematic review concluded that romiplostim is effective and generally well tolerated in patients 65 years of age and older with ITP. Complications included nonsignificant trends toward increased risks of grade ≥3 bleeding and thromboembolic events. [71]

Caveats for the use of romiplostim, and other TPO-mimetics, are as follows:

  • Abrupt discontinuation of these agents, or non-adherence to their therapeutic regimens, can result in a rapid nadir in platelet counts, often to levels that may predispose to catastrophic bleeds.
  • A variable percentage (around 30%) of patients who have achieved complete remission with TPO-mimetic therapy may maintain a durable remission after tapering of the TPO-mimetic. There are no biomarkers or specific patient characteristics that can identify patients who are likely to achieve durable remissions; use in pregnancy is not recommended but anecdotally appears to be safe.
  • Arterial and venous thrombotic events have been reported during TPO-mimetic use, but other than perhaps portal vein thrombosis, such events do not occur any more frequently than in those ITP patients receiving standard non–TPO-mimetic therapy. [72]


Like romiplostim, eltrombopag also became available in 2008. In 2015, the US Food and Drug Administration expanded the indication for eltrombopag to include treatment of chronic ITP in patients 1 year of age and older who have not achieved an appropriate response with other medical therapy or splenectomy. [73]  An oral TPO receptor agonist, eltrombopag increases platelet counts after 8 days of daily dosing.

Eltrombopag was studied in a phase III double-blind trial in adults with previously treated ITP lasting more than 6 months and with platelet counts lower than 30,000/µL. Patients received treatment with local standard care plus eltrombopag (50 mg) or placebo for 6 months. Of 196 patients in the study, 106 (79%) patients in the eltrombopag group responded to treatment at least once, compared with 17 (28%) in the placebo group. Toxic reactions in the eltrombopag group included thromboembolic events (2%), mild increases in alanine aminotransferase levels (3%), and increased total bilirubin levels (4%). [74]

Eltrombopag has a boxed warning for the risk of severe and potentially life‐threatening hepatotoxicity. Dose reductions are needed for patients with hepatic impairment and some patients of East Asian ancestry. Eltrombopag must be taken on an empty stomach (1 hr before or 2 hrs after meals).  


Avatrombopag, an oral TPO receptor agonist, was approved by the FDA in 2019 for adults with chronic ITP who have had an insufficient response to a previous treatment. Results from a phase III randomized trial that supported the approval showed avatrombopag administration resulted in a platelet count of at least 50,000/µL at day eight of therapy in the majority of patients, with efficacy superior to placebo in maintaining platelet counts in the target range during the 6-month treatment period. [75]

Unlike romiplostim, which must be taken on an empty stomach, avatrombopag can be taken with food; unlike eltrombopag, it has not been associated with hepatotoxicity. In retrospective study of 44 adult patients with chronic ITP switched to avatrombopag after inadequate response to eltrombopag or romiplostim, 41 patients (93%) achieved a platelet response (≥50 × 109/L) and 38 patients (86%) achieved a complete response (≥100 × 109/L). [76]


Surgical Care

In persons with acute immune thrombocytopenia (ITP), splenectomy usually results in rapid, complete, and life-long clinical remission. In persons with chronic ITP, the results of splenectomy are typically less predictable than they are in patients with acute ITP. Platelet counts may not fully revert to normal values, and relapses are not uncommon after 5 years. Studies suggest that the initiation of thrombopoietin mimetics may obviate splenectomy in a significant number of adults with chronic ITP. [77]

Laparoscopic splenectomy is an interventional approach that is less invasive than traditional splenectomy and offers the promise of decreased postoperative morbidity and shorter recovery. [78, 79, 80] However, the ultimate role for laparoscopic splenectomy in ITP depends on long-term follow-up to determine whether this approach is as effective as conventional splenectomy for visual scrutiny of the abdominal cavity to identify accessory spleens.

Splenectomy results in a lifelong increased risk of sepsis from infection by encapsulated bacteria [81, 82, 83] and Babesia, as follows [84] :

  • In adults, this risk is estimated to be approximately 1%, with a fatal outcome in approximately 1 per 1500 patient-years.

  • In children, the risk of bacterial sepsis after splenectomy is estimated to be 1-2%. Many pediatricians recommend delaying splenectomy until children are 5 years of age.

  • These estimates are presumably based on early data and may be inflated, given the increased alertness to the importance of early treatment, availability of more effective antibiotics, and availability of vaccines against specific encapsulated bacteria.

  • Before one concludes that medical management and splenectomy have failed and that treatment with alternative options is needed, perform an imaging study to ensure that the problem is not associated with an accessory spleen.

In addition, splenectomy has been associated in adults with an increased incidence of venous and arterial thrombosis, [85] a twofold increase in deaths from cardiovascular disease, [86] and an increased rate of pulmonary hypertension [87] .

If elective splenectomy is planned for a child or an adult, initiate immunization with Haemophilus influenzae type b vaccine at least 14 days before surgery. [88]

Immunize adults and children older than 2 years with polyvalent Streptococcus pneumoniae vaccine and quadrivalent meningococcal polysaccharide vaccine.

Evaluate patients who have a relapse after having an initially satisfactory response to splenectomy for the possible presence of an accessory spleen. [89, 90]

  • An accessory spleen is strongly suggested if Howell-Jolly bodies appeared on the peripheral smear after splenectomy but are no longer present. However, the continued presence of Howell-Jolly bodies does not exclude an accessory spleen.

  • Imaging techniques using radionucleotide-labeled sulfur colloid, heat-damaged RBCs, or, preferably, autologous platelets provide more useful information than standard imaging with CT scanning or MRI.



Selecting a treatment program for immune thrombocytopenia (ITP) requires knowledge of current options and consultation with a hematologist.

If 6 months of medical management fails to increase the platelet count to a safe range (about 30,000/µL), splenectomy becomes an option. Early consultation with a surgeon is useful for planning management. [91, 92]

If the platelet count is less than 10 × 109/L (< 10 × 103/µL) or if the patient has other evidence of a clinically significant risk of serious hemorrhage, consult a radiologist to determine what noninterventional imaging procedures are available in case of emergency.