Immune Thrombocytopenic Purpura: Treatment & Medication

Author: Craig M Kessler, MD, Professor, Department of Medicine and Pathology, Division of Hematology/Oncology; Director, Clinical Coagulation Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Hospital Coauthor(s): S Gerald Sandler, MD, FACP, FCAP, Professor of Medicine and Pathology, Director, Transfusion Medicine, Department of Laboratory Medicine, Georgetown University Hospital; Rumina Bhanji, MD, Staff Physician, Departments of Pathology and Laboratory Medicine, Georgetown University Hospital Contributor Information and Disclosures Updated: Dec 28, 2010
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Treatment
Medical Care
The goal of medical care is to increase the platelet count to a safe level, permitting patients with immune thrombocytopenic purpura (ITP) 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.29 Although the paradigm may be shifting somewhat with the expanding experience with thrombopoietin receptor analogs in chronic ITP, the long-term consequences associated with their use remain to be established and their delayed platelet count responses are not conducive to preventing or reversing the potential of acute bleeding complications in newly diagnosed ITP. Therefore, for now, corticosteroids (ie, oral prednisone, IV methylprednisolone) or high-dose dexamethasone30,31,32 should remain the drugs of choice (DOCs) for the initial management of acute ITP. 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. IV immunoglobulin (IVIG) has been the drug of second choice (after corticosteroids) for many years.33,34 However, for Rh(D)-positive patients with immune thrombocytopenic purpura (ITP) and intact spleens, IV Rho immunoglobulin (RhIG) offers comparable efficacy, less toxicity, greater ease of administration, and a lower cost than IVIG.35,36 The limitation of using IV RhIG is the lack of efficacy in Rh(D)-negative or splenectomized patients. Also, IV RhIG induces 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 hemolysis37 disseminated intravascular coagulation (particularly in elderly individuals), and renal failure38 have been reported. Most children with acute ITP do not require treatment, and thrombocytopenia resolves spontaneously.39,40 If bone marrow aspiration is unacceptable to parents and if the diagnosis of acute ITP is equivocal, IV RhIG is an effective treatment for ITP that avoids the problem of a misdiagnosis of acute leukemia because of steroid-related changes in the marrow. In adults, the initial treatment for ITP is similar to that in children, except that additional precautions are required for persons with hypertension, peptic ulcers, recent aspirin ingestion, or other risk factors for increased bleeding.
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Aspirin inhibits platelet function by acetylating platelet cyclooxygenase, increasing the risk of bleeding because it adds a 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 X 109/L (>50 X 103/L) typically have minimal purpura, and the risk of a severe hemorrhage is low. They may be treated without a specific medication. Platelet transfusions may be required to control clinically significant bleeding but are not recommended for prophylaxis. Transfused platelets also have decreased circulation, and repeated platelet transfusions may lead to platelet alloimmunization.

Pregnant women require special consideration for delivery.41

If the platelet count is greater than 50 X 109/L (>50 X 103/L), the risk of serious hemorrhage is low, but beginning oral prednisone a week before delivery is a reasonable precaution. If the platelet count is less than 50 X 109/L (50 X 103/L) before delivery, treatment with oral prednisone and IVIG is recommended. The safety of thrombopoietin mimetics in pregnancy and breastfeeding has not been established. 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. Although the effects on an Rh(D)-positive fetus are unknown, avoiding the use of IV RhIG in this situation until safety data are available is advisable. Rarely, splenectomy may be required to manage acute hemorrhage.42

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 vinblastine, vincristine, ascorbic acid, colchicine, and interferon alfa.43,44,45,46,47,48 . In 2008, thrombopoietin receptor agonists became available for patients with chronic ITP. The limited clinical experiences with thrombopoietin mimetics are promising. 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.49 The ultimate efficacy and safety of these new agents will not be fully evaluable until data on larger numbers of patients become available.

Surgical Care
In persons with acute immune thrombocytopenic purpura (ITP), splenectomy usually results in rapid, complete, and life-long clinical remission. In persons with chronic immune thrombocytopenic purpura (ITP), the results of splenectomy are typically less predictable than they are in patients with acute immune thrombocytopenic purpura (ITP). Platelet counts may not fully revert to normal values, and relapses are not uncommon after 5 years. Laparoscopic splenectomy is an interventional approach less invasive than traditional splenectomy and offers the promise of decreased postoperative morbidity and shorter recovery.50,51 However, the ultimate role for laparoscopic splenectomy in immune thrombocytopenic purpura (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 bacteria52,53,54 and Babesia.55

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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 aged 5 years. 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 for prophylactic immunization 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. Recent studies suggest that the initiation of thrombopoietin mimetics may be splenectomy sparing in a significant number of individuals with chronic ITP.

In addition, splenectomy has also been associated in adults with an increased incidence of venous and arterial thrombosis,56 an increase in deaths from cardiovascular disease by a factor of 2,57 and an increased rate of pulmonary hypertension58 . 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.59 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.60,61
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An accessory spleen is strongly indicated 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.

Consultations
Selecting a treatment program for immune thrombocytopenic purpura (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/L), splenectomy becomes an option. Early consultation with a surgeon is useful for planning management.62,63

If the platelet count is less than 10 X 109/L (<10 X 103/L) 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.

Medication
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.64 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).65 The treatment of chronic, refractory immune thrombocytopenic purpura (ITP) may introduce risks of toxicity from medications comparable in severity to the risks of untreated thrombocytopenia. No universally effective treatments for chronic refractory ITP are available. The authors recommend either romiplostim (injection) or eltrombopag (oral) at this stage of the disease, but caution that clinical experience is limited. Long-term experience will be necessary before these new thrombopoietin receptor agonists have a clearly defined role in the management of immune thrombocytopenic purpura (ITP). The authors encourage patients to participate in formal investigational programs to support the development of effective treatments for this category.

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. 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.66 Recognizing the importance of continuous monitoring of newly licensed drugs for patients with chronic and refractory ITP, the US Federal Drug Administration (FDA) has made eltrombopag and romiplostim available to qualified patients via physicians who have registered to participate in manufacturers' safety monitoring programs in the FDA's Risk Evaluation and Mitigation Strategy (REMS) program, which was part of the FDA Amendments Act of 2007. 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.67,68 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.69,70,71 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.49 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 2008.72,73

Corticosteroids
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.

Prednisone (Deltasone, Orasone, Sterapred) Oral corticosteroid that is used most frequently because of its relatively low cost, known adverse effects, and long-term 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.
y y y y Adult

Dosing Interactions Contraindications Precautions

1-2 mg/kg PO; if treatment is not urgent or if the patient is at risk for adverse effects (eg, diabetes, hypertension, psychiatric illness), 0.25 mg/kg/d (30-40 mg/d) may be adequate
Pediatric

4-8 mg/kg/d PO; 1.5-2 mg/kg/d may be adequate for nonurgent situations or when the patient is at high risk of adverse effects (eg, diabetes, psychiatric illness)
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Dosing Interactions Contraindications Precautions

Coadministration with estrogens may decrease the clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase the metabolism (consider increasing the maintenance dose); monitor for hypokalemia with coadministration of diuretics
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Dosing

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Interactions Contraindications Precautions

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
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Dosing Interactions Contraindications Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Monitor for signs of acute adverse reactions, including hypertension, hyperglycemia, activation of tuberculosis or a systemic fungal infection, or acute psychosis; long-term maintenance therapy is associated with other manifestations of hypercortisolism (ie, Cushing syndrome), including facial swelling, acne, cataracts, weight gain, and growth retardation in children; acute stress (eg, bacterial sepsis) may require IV steroid replacement because of inadequate adrenal cortical function.

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.
y y y y Adult

Dosing Interactions Contraindications Precautions

1 g/d IV
Pediatric

30 mg/kg/d IV

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Dosing Interactions Contraindications Precautions

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects
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Dosing Interactions Contraindications Precautions

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

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Dosing Interactions Contraindications Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Caution in patients with hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Blood Products
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.

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.

y y y y Adult

Dosing Interactions Contraindications Precautions

50 mcg/kg IV single infusion; followed by 20-40 mcg/kg prn; in patients whose hemoglobin concentration is >8 g/dL; off-label dose of 75 mcg/kg may increase efficacy without adverse effect
Pediatric

Administer as in adults
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Dosing Interactions Contraindications Precautions

None reported
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Dosing Interactions Contraindications Precautions

Not recommended in Rh(D)-negative persons or after splenectomy; should not be used if hemoglobin concentration is <8 g/dL; persons with immunoglobulin A (IgA) deficiency and anti-IgA who are at risk for anaphylactic or anaphylactoid reaction to all plasma-containing biologics, including IV RhIG; do not use to treat ITP in pregnancy if Rh blood type of fetus is Dpositive or unknown
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Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

Standard dose of IV RhIG (anti-D) to treat ITP is >10-fold greater than dose for standard antenatal Rh immunoprophylaxis; effect of large dose on Rh(D)-positive fetal RBCs unknown;

precaution does not apply to use for Rh immunoprophylaxis in pregnancy because of the reduced dose for that indication

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.
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Dosing Interactions Contraindications Precautions

Begin with 1 g/kg IV at starting rate of 0.5 mL/kg/h (5% solution); not to exceed 4 mL/kg/h; if no adverse reactions, 10% solution may be started at 0.5 mL/kg/h and increased to 8 mL/kg/h; repeat q3-4wk when indicated by decreasing platelet count
Pediatric

Begin with 1 g/kg IV at starting rate of 0.5 mL/kg/h (5% solution); not to exceed 4 mL/kg/h; repeat q3-4wk when indicated by decreasing platelet count
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Dosing Interactions Contraindications Precautions

Increases toxicity of live-virus vaccine (measles, mumps, and rubella [MMR]); do not administer within 3 mo of vaccination
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Dosing Interactions Contraindications Precautions

Documented hypersensitivity; IgA deficiency; antiIgE/IgG antibodies

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Dosing

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Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

Caution in patients with aseptic meningitis, renal insufficiency, and pulmonary insufficiency and thrombosis; acute reactions may include flushing, headaches, chills, nausea, or vomiting

Immunosuppressive Antimetabolites
Immunosuppressive antimetabolites are used in patients with immune thrombocytopenic purpura (ITP) to reduce production of abnormal autoantibodies.

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.
y y y y Adult

Dosing Interactions Contraindications Precautions

2 mg/kg/d PO/IV
Pediatric

Not established
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Dosing Interactions Contraindications Precautions

Toxicity increases with allopurinol; concurrent use with angiotensin-converting enzyme (ACE) inhibitors may induce severe leukopenia; may increase the levels of methotrexate metabolites and decrease the effects of anticoagulants, neuromuscular blockers, and cyclosporine
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Dosing Interactions Contraindications Precautions

Documented hypersensitivity
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Dosing Interactions Contraindications Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions

Increases the risk of neoplasia; caution in the presence of liver disease and renal impairment; hematologic toxicities may occur

Synthetic Antineoplastic Drugs

Synthetic antineoplastic drugs are chemically related to nitrogen mustards. These agents inhibit cell growth and proliferation.

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.
y y y y Adult

Dosing Interactions Contraindications Precautions

2 mg/kg/d PO or 1-1.5 g/m2 q2-4mo IV infusion; some patients require dosing more frequent than this

Pediatric

Not established
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Dosing Interactions Contraindications Precautions

Allopurinol may increase the risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and the antimicrobial effects of quinolones; chloramphenicol may increase the half-life while decreasing metabolite concentrations; may increase the effect of anticoagulants; coadministration with high doses of phenobarbital may increase the rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
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Dosing Interactions Contraindications Precautions

Documented hypersensitivity; severely depressed bone marrow function

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Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

Vigorous IV hydration is required to minimize the risk of hemorrhagic cystitis after infusion; carcinogenesis, leukemia after long-term use, marrow suppression, alopecia, mutagenesis, impairment of fertility (interferes with oogenesis and spermatogenesis), cardiac toxicity, and hemorrhagic cystitis

Androgens
The steroidogenic properties of androgens may modulate the immune system.

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.
y y y y Adult

Dosing Interactions Contraindications Precautions

200-600 mg/d PO; after several wk, may reduce to 50-100 mg/d to decrease adverse effects
Pediatric

Not established
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Dosing Interactions Contraindications Precautions

Decreases insulin requirements and increases the effects of anticoagulants

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Dosing Interactions Contraindications Precautions

Documented hypersensitivity; seizure disorders, hepatic or renal insufficiency, lactation, and conditions influenced by edema
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Dosing Interactions Contraindications Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Adverse effects include amenorrhea, hirsutism, acne, seborrhea, headache, fluid retention, muscle cramps, and abnormal liver function results (41% of patients)

Monoclonal Antibodies
Monoclonal antibodies are chimeric murine-human monoclonal antibodies directed against CD20 on B lymphocytes.

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.
y y y y Adult

Dosing Interactions Contraindications Precautions

375 mg/m2 IV infusion qwk for 4 doses

Pediatric

Not established
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Dosing Interactions Contraindications Precautions

Decreases circulating B lymphocytes

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Dosing Interactions Contraindications Precautions

Patients with known anaphylaxis or IgE-mediated hypersensitivity to murine proteins

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Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

If there is no response to corticosteroids, IV RhIG, or IVIG, the usual course is splenectomy, but case reports and small series have indicated impressive results with the standard dose of rituximab; on the basis of limited information, it may be better than splenectomy in achieving sustained remission with minimal adverse effects.

Thrombopoietin-Receptor Agonists
These new agents directly stimulates bone marrow platelet production.70

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. Only available through the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate) program, a program designed to promote informed risk-benefit decisions before initiating treatment. For more information, see http://www.nplate.com or call (877) NPLATE1 (877-675-2831).
y y y y Adult

Dosing Interactions Contraindications Precautions

1 mcg/kg (actual body weight) SC initially; adjust in increments of 1 mcg/kg SC qwk to achieve platelet count of 50 X 109/L or greater (median dose in clinical trials was 2 mcg/kg); not to exceed 10 mcg/kg/wk If the platelet count is not adequate to control bleeding after 4 wk at maximum dose, discontinue and continue monitoring platelet count for 2 wk.
Pediatric

<18 years: Not established

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Dosing Interactions Contraindications

Precautions

None reported; data limited

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Dosing Interactions Contraindications Precautions

None known
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Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

May increase the risk of bone marrow fibrosis and bone marrow reticulin formation; thrombotic and thromboembolic complications may result from excessive platelet count increases; not to be used to normalize platelet counts; worsened thrombocytopenia has been reported upon discontinuation; may increase the risk of bleeding; antibody development has been reported (although no correlation between antibody activity and clinical effectiveness or safety); stimulation of TPO receptor may increase the risk for hematologic malignancies

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. Prescribers must enroll in Promacta Cares program. Only available through restricted distribution program. Program phone number is (877) 9-PROMACTA (877-977-6622).
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Dosing Interactions Contraindications Precautions

Adult

50 mg PO qd 1 h ac or 2 h pc East Asian ancestry or moderate-to-severe hepatic insufficiency: 25 mg PO qd Use lowest dose to achieve and maintain platelet count 50 X 109/L to reduce risk of bleeding; not to exceed 75 mg/d; discontinue if platelet count not increased after 4 wk at maximum dose or if platelet count increases substantially

Follow-up
Complications
Inform patients with immune thrombocytopenic purpura (ITP) who have undergone splenectomy that their natural defense against acute bacterial infection is decreased. Any fever, particularly with signs or symptoms that suggest something more serious than the common cold, requires prompt medical attention and, possibly, early antibiotic treatment. Children with a fever (temperature of 38.8 C or 102 F) should receive IV antibiotics until bacterial infection is excluded.

Prognosis
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Children o More than 80% of children with untreated immune thrombocytopenic purpura (ITP) have a spontaneous recovery with completely normal platelet counts in 2-8 weeks. o Fatal bleeding occurs in 0.9% upon initial presentation. o The goal of prompt treatment with prednisone and IV RhIG or IVIG is to accelerate the increase in platelet count to avert a serious hemorrhage. o Data on this subject are difficult to locate. o Fatal intracerebral hemorrhage occurs rarely in children who have been treated with prednisone and IV RhIG or IVIG for at least 2 days. Adults o Approximately 60-90% of adults with immune thrombocytopenic purpura (ITP) respond with an increased platelet count after treatment with prednisone or prednisone and IV RhIG or IVIG. o Of those adults who do not maintain an increased platelet count and who require splenectomy, approximately two thirds have a sustained response and 10-15% have a partial response.74

Miscellaneous
Medicolegal Pitfalls

Permanent neurologic damage o Although nondefinitive, the guidelines for the risk of a serious hemorrhage that complicates immune thrombocytopenic purpura (ITP) should be followed. o Inform all patients and/or their parents about the potential risks of serious spontaneous or trauma-induced hemorrhage, including intracranial bleeding and its consequences. Informed consent for blood products o IV RhIG and IVIG are manufactured from pooled human plasma. o Manufacturers have treated these products with various methods to reduce the risk of transfusion-transmitted viral infections; inform all patients treated with a blood product about the manufacturer's efforts to reduce this risk. Pregnancy o Management of immune thrombocytopenic purpura (ITP) that develops during pregnancy requires the close cooperation of the patient, the obstetrician, and the hematologist. o Most pharmaceuticals used in the treatment of immune thrombocytopenic purpura (ITP) are not categorized for use during pregnancy. o Obtaining informed consent is essential. o Emphasize to the mother the importance of fetal health and the risk of fetal intracranial bleeding with maternal immune thrombocytopenic purpura (ITP).