Immune Thrombocytopenia (ITP)


Treatment for immune thrombocytopenia (ITP) aims to elevate platelet counts back to safe levels while the patient achieves clinical remission either spontaneously or with the aid of treatment-induced remission.1

After excluding other diagnoses and confirming ITP, it is important to first observe acute patients for spontaneous resolution without treatment. If resolution is not achieved, treatment of acute ITP depends on many factors, including patient age at disease onset and patient response to treatment. Chronic cases of ITP may respond to similar therapies, however, if multiple pharmaceutical therapies fail and symptoms exacerbate, splenectomy may be necessitated.

Medical Treatment

Corticosteroids

Oral prednisone or dexamethasone is usually the first-line therapy for acute ITP, especially in urgent care settings. Steroids reduce the rate of platelet destruction, promote primary hemostasis, and decrease bleeding and bruising.1 

Any bone marrow biopsies should be performed prior to initiating treatment with corticosteroids due to their ability to alter bone marrow morphology.1 

Complications associated with corticosteroid administration include ulcers, gastritis, growth retardation, hypertension, avascular necrosis, personality changes, opportunistic infections, insomnia, osteoporosis, and diabetes.3 

Intravenous Immunoglobulin

Intravenous immunoglobulin (IVIG) treatment impairs the clearance of opsonized platelets. It may also potentially cause increased clearance of antiplatelet antibodies to reverse thrombocytopenia.3 IVIG may be chosen following steroids if a rapid increase in platelet count is critical.1

Infusion-related adverse effects include fever, chills, nausea, and headache. Rarer adverse effects that are more serious include aseptic meningitis, thromboembolic events, and renal impairment or failure.3

Intravenous Rhesus Anti-D Immunoglobulin

For patients who test positive for the rhesus (Rh) D antigen and have intact spleens, treatment using intravenous Rh anti-D immunoglobulin (RhIG) is preferred over IVIG treatments.1 RhIG infusions are cheaper, safer (less toxic), and easier to administer than IVIG therapy, and they typically involve shorter lengths of stay in the hospital.1,3 

Treatment-related side effects include fever, chills, nausea, and headache. A decrease in hemoglobin of usually no greater than 2 g/dL occurs due to treatment-related hemolysis. More serious side effects include severe hemolysis, renal failure, and disseminated intravascular coagulation.1,3 Since hemolysis is a common adverse effect, intravenous Rh anti-D antibody treatment should not be used to treat patients with hemoglobin levels lower than 8 g/dL.1 

Read more about ITP therapies

Rituxan®

Rituxan (rituximab) is a second-line pharmaceutical therapy used to treat refractory ITP when first-line steroids or IVIG treatments have failed or when patients no longer tolerate them. Rituximab is currently the best available treatment option for refractory ITP.3 

Rituximab is a monoclonal antibody that works by decreasing the number of B lymphocytes that produce autoantibodies, such as those that attack platelets in ITP.3

Rituximab-induced side effects include neutropenia and reactivation of chronic infections, such as tuberculosis.3

Immunosuppressants

Immunosuppressants, such as Imuran® (azathioprine), CellCept® (mycophenolate mofetil), cyclophosphamide, and cyclosporine, work to decrease the strength of the immune system by inhibiting the activity of T cells.3

Aczone®

Aczone (dapsone) is classified as an antibiotic and anti-inflammatory medication that was originally indicated for leprosy, dermatitis herpetiformis, and other skin ailments.4 However, dapsone is also recommended as a second-line immunosuppressant agent for patients with refractory ITP, as it has also been shown to reverse thrombocytopenia in 40% to 50% of patients after about 1 month.3

Thrombopoietin Receptor Agonists/Mimetics

Thrombopoietin (TPO) receptor agonists or mimetics, such as Nplate® (romiplostim), Promacta® (eltrombopag), and Doptelet® (avatrombopag), have recently been developed and are second-line agents used to treat chronic ITP.1 

TPO agents work as platelet growth factors, mimicking the action of endogenous thrombopoietin on megakaryocytes and their precursors, promoting megakaryocyte differentiation to increase platelet production and compensate for the autoimmune destruction of platelets in ITP.5

Platelet Transfusions

Patients with ITP needing to undergo emergency surgery or those experiencing severe bleeding episodes that require emergency care may require platelet transfusions to immediately elevate platelet counts to prophylactically reduce the risk of bleeding during surgery or to stop current bleeding episodes.6

Tavalisse®

The US Food and Drug Administration (FDA) has approved the use of Tavalisse (fostamatinib) to treat patients with chronic, refractory ITP. Fostamatinib is the first spleen tyrosine kinase inhibitor approved in the United States. After the failure of other treatments to stimulate a platelet response in patients with chronic, refractory  ITP, studies demonstrate improved platelet responses and decreased bleeding episodes while taking fostamatinib compared to those given a placebo.1

Other Treatments

Several other treatments have been used to treat patients with ITP; however, treatment efficacy is less certain. These treatments include danazol, alemtuzumab, azathioprine, vinblastine, vincristine, ascorbic acid, colchicine, interferon alfa, and vinca alkaloids. Dapsone is also included in this list of unproven ITP treatments.1,3

Targeted Therapies

As the understanding of the pathophysiology of ITP advances, new therapies are currently being developed to target specific pathways and mechanisms that contribute to ITP. These therapies target neonatal Fc receptor inhibitors, Bruton tyrosine kinase, and the complement pathway.7

Read more about ITP experimental therapies

Surgical Treatment

Splenectomy is not a favored option to treat ITP in children due to the increased risk of postsplenectomy infection and sepsis from encapsulated organisms.3 It is recommended to delay splenectomy for at least 12 months after initial ITP diagnosis to allow for spontaneous or treatment-induced remission to occur.8 

Indications for splenectomy include severe menorrhagia, life-threatening hemorrhaging, lifestyle limitations due to ITP, and chronic, refractory ITP that has not responded to multiple other treatment options.3 

Patients who undergo splenectomy demonstrate a response rate of 50% to 70% and achieve the most durable response in terms of sustained elevation of platelets compared with other treatments.8 Splenectomy usually results in rapid, complete, life-long clinical remission of ITP since the spleen is the primary site of ITP pathogenesis.2 

Read more about ITP surgical management

References

  1. Kessler CM. Immune thrombocytopenia (ITP) treatment & management: medical care. Medscape. Updated January 7, 2021. Accessed October 25, 2022.
  2. Kessler CM. Immune thrombocytopenia (ITP) treatment & management: surgical care. Medscape. Updated January 7, 2021. Accessed October 25, 2022.
  3. Warrier R, Chauhan A. Management of immune thrombocytopenic purpura: an update. Ochsner J. 2012;12(3):221-227. 
  4. Dapsone. RxList. Updated September 30, 2020. Accessed October 25, 2022.
  5. Al-Samkari H, Kuter DJ. Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. Ther Adv Hematol. 2019;10:2040620719841735. doi:10.1177/2040620719841735
  6. Khan AI, Anwer F. Platelet transfusion. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated May 1, 2022. Accessed October 25, 2022.
  7. Provan D, Semple JW. Recent advances in the mechanisms and treatment of immune thrombocytopenia. eBioMedicine. 2022;76:103820. doi:10.1016/j.ebiom.2022.103820
  8. Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune thrombocytopenia: down but not out. Blood. 2018;131(11):1172-1182. doi:10.1182/blood-2017-09-742353

Reviewed by Harrshi Dhingra, MD, on 10/27/2022.