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Immune Thrombocytopenic Purpura Medication

Author: Craig M Kessler, MD, MACP; Chief Editor: Emmanuel C Besa, MD more... Updated: Apr 8, 2013

Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Treatment plans
Given the goals and considerations mentioned above, treatment of acute immune thrombocytopenic purpura (ITP) requires considerable individualization.[66] The present authors recommend the general approach for children with acute immune thrombocytopenic purpura (ITP) discussed below. For initial (induction) treatment (platelet count 20-30 X 109 /L [20-30 X 103 /L] and/or mucocutaneous bleeding), one regimen is prednisone 4-8 mg/kg/d with the intent of a rapid and complete taper after 7-10 days or when the platelet count reaches 50 X 109 /L (50 X 103 /L), whichever occurs first. In critical situations, an IV infusion of a corticosteroid may be preferable. Second-line (maintenance) treatment is IV RhIG 75/g/kg (off-label dose) for the Rh-positive patient or IVIG 1.0 g/kg for the Rh-negative patient. If the patient has clinically significant purpura or bleeding at presentation, consider infusing the first dose of IV RhIG or IVIG at the time of initial therapy with corticosteroids. Repeat the infusions at 3- to 4-week intervals (maintenance) until a satisfactory platelet count is achieved. If the platelet count is not maintained after 3-4 infusions, the patient's case might be refractory, and a different treatment should be considered. Conditions refractory to IV RhIG may respond to IVIG, and vice versa. If the patient's hemoglobulin level decreases to 8.0 g/dL during treatment with IV RhIG, temporarily switch to IVIG until the level recovers. In this situation, the patient's condition should not be considered refractory to IV RhIG. Conventional third-line treatment is splenectomy. However, recognizing the life-long potential adverse effects of splenectomy and the promising reports of responses to rituximab, the present authors now consider a course of rituximab 375 mg/m2 per week for 4 doses (off-label indication) before splenectomy (which becomes fourth-line therapy).[67] Rituximab at a standard dose of 375 mg/m2 per week for 4 weeks appears to be safe and effective, allowing nearly 40% of patients with ITP to achieve a long-term response and splenectomy-sparing effect in one study.[68]

Recommended general approach for adults with chronic immune thrombocytopenic purpura
Adults whose disease is not controlled with a prednisone-induced increase in platelet count that is maintained by IV RhIG or IVIG and whose conditions do not respond to 4 weekly infusions of rituximab are candidates for splenectomy. After these serial experiences, such patients are likely to have had thrombocytopenia for at least 6

months and, therefore, are categorized as having chronic immune thrombocytopenic purpura (ITP). Eltrombopag or romiplostim offer potential maintenance of safe levels of platelet counts for adults who qualify by having ITP for at least 6 months and whose conditions are refractory to conventional medical management (prednisone, IV RhIG, IVIG, rituximab), and whose platelet count is not maintained in a satisfactory range after splenectomy.[69] The treatment of chronic, refractory immune thrombocytopenic purpura (ITP) may introduce risks of toxicity from medications that are comparable in severity to the risks of untreated thrombocytopenia. These treatments also may impact adversely on the patient's quality of life.[70] For patients with chronic refractory immune thrombocytopenic purpura (ITP) who have access to investigational programs, the authors encourage them to participate in controlled clinical trials to support the development of effective treatments for this category.

Thrombopoietin-receptor agonists
Most conventional treatments for immune thrombocytopenic purpura (ITP) act by decreasing destruction of autoantibody-coated circulating platelets. Several promising drugs are in clinical trials which increase platelet counts in persons with immune thrombocytopenic purpura (ITP) by increasing the number of platelets produced and released by the bone marrow.[71, 72] Romiplostim (formerly AMG531) was approved by the FDA in August 2008, and is a thrombopoiesis-stimulating protein Fc-peptide fusion protein ("peptibody") that increases platelet counts in patients with acute and chronic immune thrombocytopenic purpura (ITP) without reports of significant toxicity.[73, 74, 75] A multicenter, randomized, controlled study evaluated the efficacy and side-effect profile of romiplostim compared with the standard of care for adults with immune thrombocytopenia. Compared with the standard of care, the patients in the romiplostim group had a higher rate of a platelet response, lower incidence of treatment failure and splenectomy, less bleeding and fewer blood transfusions, and a higher quality of life.[51] Promacta/Revolade (eltrombopag) significantly raised platelet counts and lowered the bleeding risk in clinical trials for the short-term treatment of patients with chronic idiopathic thrombocytopenic purpura (immune thrombocytopenic purpura [ITP]). This drug was also approved by the FDA in 2008.[76, 77] . A phase 3 double-blind, placebo-controlled study was conducted in adults with previously treated immune thrombocytopenia lasting more than 6 months with platelet counts lower than 30,000/L.[78] The study compared treatment with local standard care plus eltrombopag (50 mg) or matching placebo once daily 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%).

Corticosteroids
Class Summary
Corticosteroids are the treatment of choice for initial management of acute ITP. Increase the platelet count by decreasing splenic uptake of autoantibody-coated platelets and by decreasing synthesis of autoantibody. Dosages must be tapered after a safe platelet count is achieved, and the drug is replaced with IV RhIG or IVIG to avoid serious complications of chronic hypercorticism. View full drug information

Prednisone (Deltasone, Orasone, Sterapred)

Oral corticosteroid that is used most frequently because of its relatively low cost, known adverse effects, and longterm clinical record. DOC for initial treatment of ITP in children and adults. For aggressive treatment, may be combined with IV RhIG or IVIG. In emergency, replace PO prednisone with IV methylprednisolone. View full drug information

Methylprednisolone (Solu-Medrol)
DOC for the initial management of severe bleeding tendency in ITP. IV is recommended when the most rapid and reliable treatment of ITP is required. In this situation, combine with IV RhIG in qualified Rh(D)-positive patients or

IVIG in Rh(D)-negative patients or unqualified Rh(D)-positive patients.

Blood Products
Class Summary
Blood products are used to improve clinical and immunologic aspects of immune thrombocytopenic purpura (ITP). These products may decrease autoantibody production and increase solubilization and removal of immune complexes. View full drug information

IV RhIG (WinRho SDF)

Specialized immunoglobulin product manufactured from pools of plasma from Rh(D)-negative persons and alloimmunized to D blood group antigen. Subjected to anion-exchange column chromatography to permit IV infusion and solvent-detergent treatment and nanofiltration to reduce infectivity by lipid-enveloped viruses. Induces immune RBC hemolysis in Rh(D)-positive recipients, decreasing function of mononuclear macrophages (reticuloendothelial blockade) and sparing immunoglobulin-coated platelets from splenic destruction. View full drug information

IVIG (Gamimune, Gammagard, Sandoglobulin)

Large dose of 1 g/kg induces decreased function of mononuclear macrophages (reticuloendothelial blockade), sparing immunoglobulin-coated platelets from splenic destruction. Used with IV methylprednisolone to manage acute ITP in children. Decreased time to an increased platelet count compared with IV RhIG, but the difference does not appear to be clinically significant. Compared with IV RhIG, associated with more adverse effects, longer infusions, and increased cost, causing many hematologists to prefer IV RhIG as a supplement to corticosteroids, at least for Rh(D)-positive patients.

Immunosuppressive Antimetabolites
Class Summary
Immunosuppressive antimetabolites are used in patients with immune thrombocytopenic purpura (ITP) to reduce production of abnormal autoantibodies. View full drug information

Azathioprine (Imuran)
May be effective in some patients with ITP whose conditions do not or no longer have response to corticosteroids, IV RhIG, or IVIG. May be used with prednisone to reduce dose of prednisone or as another PO medication to delay splenectomy.

Synthetic Antineoplastic Drugs

Class Summary
Synthetic antineoplastic drugs are chemically related to nitrogen mustards. These agents inhibit cell growth and proliferation. View full drug information

Cyclophosphamide (Cytoxan)
May be useful in some patients whose conditions do not or no longer have a response to corticosteroids, IV RhIG, IVIG, or splenectomy. Induces less of a decrease in platelet count than other immunosuppressive alkylating agents.

Androgens
Class Summary
The steroidogenic properties of androgens may modulate the immune system. View full drug information

Danazol (Danocrine)
May impair the clearance of immunoglobulin-coated platelets and decreases autoantibody production. Increased platelet counts in 40-50% of patients, particularly postmenopausal women.

Monoclonal Antibodies
Class Summary
Monoclonal antibodies are chimeric murine-human monoclonal antibodies directed against CD20 on B lymphocytes. View full drug information

Rituximab (Rituxan)
Chimeric monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Antibody is IgG kappa immunoglobulin with murine light- and heavy-chain variable sequences and human constant region sequences.

Thrombopoietin-Receptor Agonists
Class Summary
These new agents directly stimulates bone marrow platelet production.[74] View full drug information

Romiplostim (Nplate)
An Fc-peptide fusion protein (peptibody) that increases platelet production through binding and activation of the thrombopoietin (TPO) receptor, a mechanism similar to endogenous TPO. Indicated for chronic immune (idiopathic) thrombocytopenic purpura in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. View full drug information

Eltrombopag (Promacta)
Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. Indicated for thrombocytopenia associated with chronic idiopathic thrombocytopenic purpura in patients experiencing inadequate response to corticosteroids, immunoglobulins, or splenectomy. Not for use to normalize platelet counts, but used when clinical condition increases bleeding risk.

Contributor Information and Disclosures

Author Craig M Kessler, MD, MACP Professor, Department of Medicine and Pathology, Division of Hematology/Oncology, Georgetown University School of Medicine; Director, Clinical Coagulation Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Hospital

Disclosure: NovoNordisk Honoraria Consulting; NovoNordisk Grant/research funds Other; Baxter-Immuno Honoraria Consulting; Octapharma Honoraria Speaking and teaching; Octapharma Grant/research funds None; Amgen Consulting fee Consulting; Bayer Review panel membership Coauthor(s) S Gerald Sandler, MD, FACP, FCAP Professor of Medicine and Pathology, Director, Transfusion Medicine, Department of Laboratory Medicine, Georgetown University Hospital S Gerald Sandler, MD, FACP, FCAP is a member of the following medical societies: American Association of Blood Banks, College of American Pathologists, and International Society of Blood Transfusions Disclosure: Nothing to disclose. Specialty Editor Board Michael Paul Kosty, MD Associate Director, Associate Professor, Department of Internal Medicine, Divisions of Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic Michael Paul Kosty, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, and Phi Beta Kappa Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis Disclosure: Nothing to disclose. Chief Editor Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences Disclosure: Nothing to disclose. Additional Contributors The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author S Gerald Sandler, MD, FACP, FCAP, to the development and writing of this article. The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor

Rumina Bhanji, MD to the development and writing of this article.

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