Immune Thrombocytopenia (ITP)


In 2019, the American Society of Hematology (ASH) published revised guidelines for the diagnosis and management of immune thrombocytopenia (ITP). To update its prior (2011) guidelines, ASH formed a multidisciplinary panel of 8 clinical experts on adult ITP, 5 clinical experts on pediatric ITP, 2 methodologists with expertise in ITP, and 2 patient representatives. Using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the members of the panel reviewed and evaluated current research knowledge.1

The panelists noted the lack of large randomized clinical trials in ITP management, along with the widespread variation and lack of standardization in practice. They used evidence to inform their recommendations for the first- and second-line management of adults and children with ITP.1 The consensus report also provided updated recommendations for the diagnosis and treatment of ITP.3

Diagnosis of ITP

Diagnostic Testing

In adults and children with primary ITP, the diagnosis is one of exclusion, given that no one diagnostic test can confirm the presence of ITP. The initial workup for primary ITP includes3:

  • Complete patient and family history
  • Physical examination
  • Complete blood cell (CBC) count and reticulocyte count
  • Peripheral blood smear analysis

If isolated thrombocytopenia, evidenced by platelet counts below 100 x 109/L,4 is present in the absence of anemia or other features on these tests, bone marrow examination is not required to confirm an initial diagnosis of ITP.3 Bone marrow aspiration and biopsy, flow cytometry, and cytogenetic studies are recommended diagnostic tests for patients with ITP that relapses following a period of remission after initial treatment. Bone marrow examination is also recommended before splenectomy in cases of chronic, refractory ITP to rule out alternative diagnoses, such as myelodysplastic syndrome and bone marrow failure.3

Read more about ITP diagnosis

Comorbidity Testing

As some medical conditions may result in a secondary ITP onset, additional testing may help differentiate between primary and secondary ITP.  Tests should detect the following comborbidities3:

  • Hepatitis B and C
  • HIV infection
  • Helicobacter pylori infection (urea breath test or stool antigen test)
  • Immunodeficiency syndromes (quantitative immunoglobulin test, especially in patients about to undergo intravenous immunoglobulin [IVIG] therapy or in children with persistent or chronic ITP)
  • Drug-induced thrombocytopenia (review of the patient’s current medications)
  • Other autoimmune conditions, such as lupus, rheumatoid arthritis, antiphospholipid syndrome, and autoimmune thyroiditis (antinuclear antibody, antiphospholipid antibody, anti-thyroid antibody, and thyroid function tests)3

In most cases, treatments may be similar for primary and secondary ITP. However, treatment may be more effective in secondary cases when the therapy is focused on underlying cause.3 

Read more about ITP comorbidities

Additional testing 

Other tests of potential utility may include3:

  • Coagulation tests to determine risk for bleeding
  • Thrombopoietin level
  • Reticulated platelet/immature platelet fraction
  • Tests for other persistent or acute infections, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and parvovirus infection

Depending on the duration of symptoms, acute (newly diagnosed) ITP (0-3 months), persistent ITP (3-12 months), or chronic ITP (>12 months) may be diagnosed.3 

Inpatient Management

The ASH 2019 guidelines recommend inpatient management for adults with newly diagnosed ITP if their platelet count is below 20 x 109/L, even if they are asymptomatic or have only minor symptoms.1,2 

Patients of any age with more significant bleeding should receive inpatient emergency care. Recommended therapies for life-threatening episodes of bleeding include IV corticosteroids and often IVIG to improve the platelet count within 24 hours. IVIG therapy, with or without significant bleeding, may necessitate inpatient admission.1 Platelet transfusions, especially in the case of emergency surgery or intracranial hemorrhaging, should not be postponed.3 

Treatment with thrombopoietin-receptor agonists (TPO-RAs) should be considered for patients with ITP who present with significant bleeding that does not respond to corticosteroids, IVIG, or platelet transfusions.3 Alternative options to TPO-RAs include IV anti-D, vincristine, or vinblastine and antifibrinolytics combined with other initial therapy recommendations. Rarely, emergency splenectomy is recommended.3

Read more about ITP therapies

Outpatient Management

For adults with an established diagnosis of ITP, outpatient management is acceptable when the platelet count is below 20 x 109/L if they are asymptomatic or present with minor bleeding.1,2

The ASH guidelines recommend outpatient management over inpatient management for children with newly diagnosed ITP whose platelet level is below 20 x 109/L and who have no or mild bleeding (skin manifestations only).1,2

Observation without treatment is recommended for patients with ITP who are asymptomatic or have minor mucocutaneous bleeding with a platelet count of 30 x 109/L or higher.1,2 

Corticosteroids are the recommended treatment for patients who have newly diagnosed ITP with a platelet count below 30 x 109/L and who present with minor or more significant bleeding.1,2

More aggressive approaches consisting of high-dose steroids and additional rescue agents, such as IVIG or anti-D immunoglobulin, are warranted in cases of severe thrombocytopenia.1,2

Read more about ITP treatment

First-Line Therapies

Corticosteroids

Oral corticosteroids, especially predniso(lo)ne, dexamethasone, or the combination of dexamethasone plus Rituxan® (rituximab), are recommended as first-line therapies for patients with newly diagnosed ITP.3 

The 2019 ASH guidelines recommend against a prolonged (>6 weeks) course of prednisone in favor of a short course (≤6 weeks). The recommended initial dose of prednisone is between 0.5 and 2 mg/kg per day or 40 mg of dexamethasone per day for 4 days.1,2 

In adults with newly diagnosed ITP, the ASH guidelines recommend corticosteroids alone over rituximab or any combination of a corticosteroid plus rituximab as the first-line treatment.1,2

IVIG/IV Anti-D  

IVIG therapy is another well-documented standard first-line treatment for ITP.3 An assessment of antiplatelet antibodies and blood typing, including rhesus factor D (RhD) status, may determine the type of IVIG therapy used. IV anti-D therapy may be an alternative, cost-effective treatment in Rh(D)-positive patients who have not undergone splenectomy.3 

Subsequent Therapies

High-Dose Corticosteroids

High-dose methylpredniso(lo)ne is a second-line treatment option, with reported response rates of 80% in patients who failed first-line therapies.3

TPO-RAs

Robust evidence supports the use of 3 TPO-RAs — Promacta® (eltrombopag), Doptelet® (avatrombopag), and Nplate® (romiplostim) — as second-line therapies in patients with ITP.3 Eltrombopag is considered more cost-effective than romiplostim.2

Monoclonal Antibodies

Rituximab and Tavalisse® (fostamatinib) are possible second- or third-line treatments for patients with ITP.3 Fostamatinib achieved clinically meaningful response rates in patients with chronic ITP who previously failed splenectomy, TPO-RA therapy, and/or rituximab treatment.5

Read more about ITP experimental therapies

Splenectomy

Splenectomy should be considered a viable alternative treatment for patients, especially adults, with persistent, chronic ITP and significant symptoms that remain unresponsive to first-line therapies.3

It is recommended that splenectomy be avoided for the first 12 months following an initial diagnosis of ITP and in children younger than 5 years old to allow spontaneous or treatment-induced remission.3 Splenectomy is rarely indicated in pediatric ITP as the majority of children recover spontaneously. Previous splenectomy is associated with worsening of maternal ITP in pregnancy with higher risk of neonatal thrombocytopenia.3

Read more about ITP surgical management

Other Treatments

Other possible medical treatments for ITP for which the supporting evidence is less robust include3:

  • Imuran® (azathioprine)
  • Aczone® (dapsone)
  • CellCept® (mycophenolate mofetil)
  • Cyclosporin A
  • Cyclophosphamide
  • Danazol
  • Vinca alkaloids

The updated 2019 ASH guidelines recommend a TPO-RA over rituximab and rituximab over splenectomy for second-line therapy in patients with ITP that has lasted 3 months or longer.1,2 The risks of each of the treatments should be discussed with the patient.2 

Pregnancy and ITP

The target platelet level that is considered safe during pregnancy is between 20 and 30 x 109/L. A platelet count of 50 x 109/L or higher is recommended for delivery and for pregnant women receiving anticoagulation who may have risk factors like anticardiolipin antibody syndrome requiring venous thromboembolism prophylaxis.3

Initial treatments for pregnant women with ITP include oral steroids or IVIG/IV anti-D in those who are Rh(D)-positive. Rituximab can be considered for patients with severe ITP during pregnancy. However, pregnant women with ITP and their newborns require monitoring for perinatal and neonatal immunosuppression and infection if they are treated with rituximab. TPO-RAs are suggested only in late pregnancy when other alternative treatments have failed.3

Medications that should never be used to treat ITP during pregnancy include vinca alkaloids, danazol, and several immunosuppressants.3

Additional Prophylactic Treatments

Additional prophylactic treatments include antibiotics and vaccination to prevent infections following splenectomy to treat chronic ITP.3 Postoperative thromboprophylaxis should be considered for patients undergoing splenectomy only if their platelet count is between 30 and 50 x 109/L.3 

References

  1. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966
  2. DeSouza S, Angelini D. Updated guidelines for immune thrombocytopenic purpura: expanded management options. Cleve Clin J Med. 2021;88(12):664-668. doi:10.3949/ccjm.88a.20201
  3. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812
  4. McCrae K. Immune thrombocytopenia: no longer ‘idiopathic.’ Cleve Clin J Med. 2011;78(6):358-373. doi:10.3949/ccjm.78gr.10005
  5. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930. doi:10.1002/ajh.25125

Reviewed by Debjyoti Talukdar, MD, on 10/30/2022.

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