Therapeutic Overview

Therapeutic Overview
The treatments for ITP are directed at different aspects of its pathogenesis. Current treatment approaches are primarily aimed at preventing or minimizing platelet destruction: either by impairing the clearance of antibody-coated platelets by the receptors expressed on tissue macrophages or by acting directly on T cells or B cells.1 The treatments outlined here are commonly used for adult ITP and sometimes used in childhood ITP if spontaneous resolution does not occur.

Current Therapies

Durability of response and side effect profile should be taken into consideration when choosing among current therapies for ITP, as described below:

  • Various corticosteroids are indicated for the treatment of ITP. Corticosteroids are initially effective in 50% to 80% of patients,1,2 and some patients go into remission when the dose is reduced or stopped.1,2 However, only 10% to 30% of ITP patients are able to manage their ITP without further treatment after corticosteroid therapy.1 Corticosteroids increase platelet production by impairing the destruction of platelets by macrophages within the bone marrow.2
    Most recently, dexamethasone—a high-dose synthetic corticosteroid—has been shown to be an effective initial therapy for some patients. Three clinical studies have suggested that the response to dexamethasone may be more sustained than that to oral prednisone but further controlled and long-term studies are needed to validate these results. Dexamethasone has not been approved by the FDA for the treatment of ITP.3,4
    Side effects of steroids vary in type and severity: short-term effects (such as fluid retention, weight gain, and mood swings) and long-term effects (such as osteoporosis, bone fractures, immunosuppression, glaucoma, and cataracts) must be considered.5
  • IVIg has been approved by the FDA for the treatment of ITP and has been found to be effective in temporarily increasing platelet count. However, counts typically relapse within 11 days.6
    Side effects of IVIg are usually mild and transient in nature and can include low-grade fever, chills, pruritus, urticaria, headache, cough, fever, vomiting, diarrhea, abdominal pain, and arthralgias. Serious side effects can include acute renal failure and rarely anaphylaxis or aseptic meningitis.5
  • Anti-RhO(D), anti-D, may be an effective alternative but cannot be used for Rh-negative or postsplenectomy patients.7 The presumed mechanism of action involves competitive binding of anti-D sensitized red blood cells to macrophage receptors in the spleen, inhibiting platelet destruction.8
    Anti-RhO(D) is indicated for the treatment of ITP. Side effects are uncommon and consist of infusion and local reactions as well as anti-D formation.5
  • Although the relationship between H. pylori and ITP has not been convincingly demonstrated, it has been speculated that H. pylori eradication therapy might have a valuable effect for some patients with ITP.9

Splenectomy

Splenectomy is often used in cases where medical treatments fail or for patients who cannot tolerate steroids. Two-thirds of patients experience an increase in platelets after surgery,2 and the response may be prompt. However, 15% to 25% of these patients may relapse, many of whom will require additional therapy.1

Splenectomy patients are at an increased risk of sepsis and other infections for the rest of their lives. They must obtain ongoing vaccination to prevent infection, prophylactic antibiotic therapy before any surgical procedure (even routine dental work), and aggressive treatment of any infection that may present.10

The Changing Course of ITP
ITP can have a highly fluctuating course due to transient effectiveness of current treatments and the common need to discontinue use of corticosteroids due to associated adverse events. This graph shows the platelet counts over time of a single patient who has had multiple, repeated treatments for ITP.

The patient was a 32-year-old woman who had a good response to prednisone, but poor responses to IVIg, postsplenectomy, prolonged treatment with prednisone kept the platelet count at a hemostatic level.11 The patient was on prednisone for at least 8 months, increasing her risk of hyperglycemia and osteoporosis.

Treatment of Refractory ITP

In cases where platelet levels are not restored over the long term following removal of the spleen, a number of other treatment options are often explored. However, few guidelines—or data from randomized clinical trials—exist on which to base a decision.1 A panel from the American Society of Hematology does, however, offer the following treatment recommendations in the case of refractory ITP. They recommend further treatment for adults if the platelet count remains under 30,000/µL after prednisone therapy and splenectomy if there is active bleeding.12 It was also the consensus of the panel that further treatment is indicated if the platelet count is below 10,000/µL, even without evidence of any bleeding.12

Refractory ITP treatments typically include:

  • Medications indicated for other conditions, such as chemotherapeutic agents. The medications listed below have been reported in the medical literature to be useful for refractory ITP. However, these medications are not approved by the FDA for the treatment of ITP. (Medications are listed alphabetically. Safety information is available from their manufacturers or in their prescribing information.4,12)
    • Azathioprine
    • Cyclophosphamide
    • Cyclosporine
    • Danazol
    • Mycophenolate mofetil (MMF)
    • Rituximab
    • Vinca alkaloids

Investigational Treatments

Some patients with severe refractory ITP will not respond to any of the currently available treatments. Treatment failure can have severe consequences. ITP patients who respond to therapy have no excess mortality compared with the general population; patients with persistent severe thrombocytopenia who do not respond within the first 2 years have substantial morbidity and mortality.13

All current treatments focus primarily on preventing platelet destruction. Increasing platelet production in ITP is an area under active investigation.

 

References

1. Bromberg ME. Immune thrombocytopenic purpura—the changing therapeutic landscape. New Engl J Med. 2006;355(16):1643-1645.
2. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346(13):995-1008.
3. Cheng Y, Wong RS, Soo YO, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003;349(9):831-836.
4. Godeau B, Provan D, Bussel J. Immune thrombocytopenic purpura in adults. Curr Opin Hematol 2007;14:535-556.
5. Physician’s Desk Reference. 61st ed. Woodvale, NJ: Thomson PDR; 2007.
6. Chong BH, Ho S-J. Autoimmune thrombocytopenia. J Thromb Haemost. 2005;3(8):1763-1772.
7. Scaradavou A, Woo B, Woloski BMR, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89(8)2689-2700.
8. Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood. 2000;95(8):2523-2629.
9. Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D. Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med. 2005;118(4):414-419.
10. Bell WR. Role of splenectomy in immune (idiopathic) thrombocytopenic purpura. Blood Rev. 2002;16(1):39-41.
11. Law C, Marcaccio M, Tam P, Heddle N, Kelton JG. High-dose intravenous immune globulin and the response to splenectomy in patients with idiopathic thrombocytopenic purpura. N Engl J Med. 1997;336(21):1494-1498.
12. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88(1):3-40.
13. Portielje JEA, Westendorp RGJ, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood. 2001;97(9): 2549-2554.