eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Immune Thrombocytopenic Purpura

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

Updated: Oct 4, 2009

Introduction

Background

Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura), or extravasation of blood from capillaries into skin and mucous membranes (petechiae).

In persons with immune thrombocytopenic purpura (ITP), platelets are coated with autoantibodies to platelet membrane antigens, resulting in splenic sequestration and phagocytosis by mononuclear macrophages. The resulting shortened life span of platelets in the circulation, together with incomplete compensation by increased platelet production by bone marrow megakaryocytes, results in a decreased platelet count.

To establish a diagnosis of immune thrombocytopenic purpura (ITP), exclude other causes of thrombocytopenia, such as leukemia, myelophthisic marrow infiltration, myelodysplasia, aplastic anemia, or adverse drug reactions. Pseudothrombocytopenia due to platelet clumping is also a diagnostic consideration.

No single laboratory result or clinical finding establishes a diagnosis of immune thrombocytopenic purpura (ITP); it is a diagnosis of exclusion.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center and Cuts, Scrapes, Bruises, and Blisters Center. Also, see eMedicine's patient education article Bruises.

Pathophysiology

In immune thrombocytopenic purpura (ITP), an abnormal autoantibody, usually immunoglobulin G (IgG) with specificity for 1 or more platelet membrane glycoproteins (GPs), binds to circulating platelet membranes.^1,2,3

Autoantibody-coated platelets induce Fc receptor-mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen.⁴ The spleen is the key organ in the pathophysiology of immune thrombocytopenic purpura (ITP), not only because platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages in the red pulp destroy immunoglobulin-coated platelets.⁵

If bone marrow megakaryocytes cannot increase production and maintain a normal number of circulating platelets, thrombocytopenia and purpura develop. Impaired thrombopoiesis is attributed to failure of a compensatory increase in thrombopoietin and megakaryocyte apoptosis.

Frequency

United States

The annual incidence of immune thrombocytopenic purpura (ITP) is estimated to be 5 cases per 100,000 children and 2 cases per 100,000 adults,⁶ but these data are not from large population-based studies. Most cases of acute immune thrombocytopenic purpura (ITP), particularly in children, are mild and self-limited and may not receive medical attention. Therefore, estimated incidences of acute immune thrombocytopenic purpura (ITP) are difficult to determine and are likely to understate the full extent of the disease. The age-adjusted prevalence of immune thrombocytopenic purpura (ITP) was reported as 9.5 per 100,000 persons in Maryland by Segal and Powe.⁷

Mortality/Morbidity

• Hemorrhage: The primary cause of long-term morbidity and mortality in patients with immune thrombocytopenic purpura (ITP) is hemorrhage.⁸
• Intracranial hemorrhage: The most frequent cause of death in association with immune thrombocytopenic purpura (ITP) is spontaneous or accidental trauma-induced intracranial bleeding. Most cases of intracranial hemorrhage occur in patients whose platelet counts are less than 10 X 10⁹/L (<10 X 10³/µL).⁹ This situation occurs in 0.5-1% of children and half are fatal.⁶ In one study, 17% of children experienced a major hemorrhage.¹⁰
• Treatment-related morbidity: To maintain a platelet count in a safe range in patients with chronic treatment-resistant immune thrombocytopenic purpura (ITP), a long-term course of corticosteroids, other immunosuppressive medications, or splenectomy may be required. In patients with immune thrombocytopenic purpura (ITP), morbidity and mortality can be related to treatment, reflecting the complications of therapy with corticosteroids or splenectomy.

Sex

• In children, immune thrombocytopenic purpura (ITP) is more common among boys compared with girls.¹¹
• In middle-aged adults, women are affected more frequently than men.⁶

Age

• Children may be affected at any age with immune thrombocytopenic purpura (ITP), but the prevalence peaks in children aged 1-6 years.¹¹
• Adults may be affected at any age, but most cases are diagnosed in women aged 30-40 years.
• Onset in a patient older than 60 years is uncommon, and a search for other causes of thrombocytopenia is warranted. The most likely causes in these persons are myelodysplastic syndromes, acute leukemia, and marrow infiltration (myelophthisis).

Clinical

History

The medical history in a patient with a clinical suspicion of immune thrombocytopenic purpura (ITP) should focus on (1) factors that suggest another disease for which thrombocytopenia is a complication¹² and (2) signs and symptoms that differentiate mild, moderate, and severe bleeding tendencies.

• Other systemic illnesses
  • In adults, thrombocytopenic purpura may be a manifestation of systemic lupus erythematosus¹³ or acute or chronic leukemia.
  • Thrombocytopenic purpura may be a manifestation of a myelodysplastic syndrome, particularly in patients older than 60 years.
  • In young children, immune thrombocytopenic purpura (ITP) may manifest as a primary immune deficiency syndrome.
• Postviral illness
  • In children, most cases of immune thrombocytopenic purpura (ITP) are acute, and onset seems to occur within a few weeks of recovery from a viral illness. The severity of symptoms of the viral illness is not correlated with the degree of thrombocytopenia.
  • Thrombocytopenia is a recognized complication after infection with Epstein-Barr virus, varicella virus, cytomegalovirus, rubella virus, or hepatitis virus (A, B, or C), although the most typical association is a vaguely defined, viral, upper respiratory infection, or gastroenteritis.
  • Transient thrombocytopenia has been reported to be associated with recent immunization with attenuated live-virus vaccines.^14,15
• Human immunodeficiency virus (HIV) infection
  • Thrombocytopenia may occur during the acute retroviral syndrome coincident with fever, rash, and sore throat.
  • Thrombocytopenia may be a manifestation of acquired immunodeficiency virus syndrome (AIDS), occurring late in the course of HIV infection.
  • Thrombocytopenia not uncommonly marks the onset of symptomatic HIV infection, particularly in people who abuse drugs.
• Drug-induced thrombocytopenia
  • Regard any medication taken by a person who develops thrombocytopenia as a potential causative agent. A history of all prescription and over-the-counter medications is required to exclude drug-related thrombocytopenia.¹⁶
  • Persons who have been sensitized (by previous exposure) to quinidine or quinine may develop immune-mediated drug purpura within hours to days of subsequent exposure. To exclude drug purpura in a person previously treated with quinidine or quinine, the history must include questions about possible exposure to over-the-counter medications, tonic water in cocktails, or bitter lemon beverages.
  • Investigate the records of patients who have been hospitalized and who develop acute thrombocytopenias for all of their medications that are listed and not listed in nursing charts. For example, people who are at risk for heparin-induced thrombocytopenia because of current or recent treatment with heparin may be receiving the heparin with the routine flushing of intravenous (IV) catheters, and this exposure may not be listed on the nursing medication sheet. Many catheters are also heparin impregnated, and unless checked, they can be a hidden cause of heparin-induced thrombocytopenia.
  • Other drugs associated with drug purpura include antibiotics (eg, cephalosporins, rifampicin), gold salts, analgesics, neuroleptics, diuretics, antihypertensives, eptifibatide (Integrilin), and abciximab (ReoPro), which is a Fab fragment of the chimeric human-murine monoclonal antibody 7E3 directed against the platelet GPIIb/IIIa receptor.
  • Acute and chronic alcohol consumption may also be associated with thrombocytopenia. In persons with chronic liver disease, hypersplenism with secondary thrombocytopenia is not uncommon.
• Bleeding tendency
  • Determine the extent and duration of the bleeding tendency to estimate the severity of the illness and the potential risk for a serious hemorrhage. Previous surgical history can often provide a useful clue regarding the acuteness of thrombocytopenia.
  • Query patients to elicit signs or symptoms of intracranial bleeding, such as headache, blurred vision, somnolence, or loss of consciousness.
  • Patients should report any recent accidental head trauma.
  • Record any bleeding, including petechiae, ecchymoses, epistaxis, menorrhagia, melena, or hematuria. Determine if bruising or bleeding is a recurrent problem.

Physical

Similar to the medical history, focus the physical examination on (1) findings that suggest another disease for which thrombocytopenia is a complication and (2) physical signs that suggest serious internal bleeding.

• General health
  • Immune thrombocytopenic purpura (ITP) is a primary illness occurring in an otherwise healthy person.
  • Signs of chronic disease, infection, wasting, or poor nutrition indicate that the patient has another illness.
• Vital signs: Hypertension and bradycardia may be signs of increased intracranial pressure and evidence of an undiagnosed intracranial hemorrhage.
• Skin and mucous membranes
  • An initial impression of the severity of immune thrombocytopenic purpura (ITP) is formed by examining the skin and mucous membranes.
  • Widespread petechiae and ecchymoses, oozing from a venipuncture site, gingival bleeding, and hemorrhagic bullae indicate that the patient is at risk for a serious bleeding complication. If the patient's blood pressure was taken recently, petechiae may be observed under and distal to the area where the cuff was placed and inflated. Suction-type electrocardiograph (ECG) leads may similarly induce petechiae.
  • Mild thrombocytopenia and a relatively low risk for a serious bleeding complication may manifest as petechiae over the ankles in patients who are ambulatory or on the back in patients who are bedridden.
• Cardiovascular system: Distant low-amplitude heart sounds accompanied by jugular venous distention may be evidence of hemopericardium.
• Abdomen
  • In children with acute immune thrombocytopenic purpura (ITP), the presence of a readily palpable spleen is not typical.
  • In an adult, hepatosplenomegaly is also atypical for immune thrombocytopenic purpura (ITP) and may indicate chronic liver and other diseases. In fact, splenomegaly excludes the diagnosis of immune thrombocytopenic purpura (ITP).
• Nervous system
  • Any asymmetrical finding of recent onset can indicate an intracranial hemorrhage.
  • Pupils should be equal in size and have intact extraocular muscles and symmetrical eye movements.
  • Balance and gait should be intact.
  • Funduscopic examination reveals whether the margins of the optic disc are blurred. Examine the patient for the presence of retinal hemorrhages and other evidence of increased intracranial pressure.

Causes

In children, most cases of immune thrombocytopenic purpura (ITP) are acute, manifesting a few weeks after a viral illness. In adults, most cases of immune thrombocytopenic purpura (ITP) are chronic, manifesting with an insidious onset, typically in middle-aged women. These clinical presentations suggest that the triggering events may be different. However, in both children and adults, the cause of thrombocytopenia (destruction of [antibody-coated] immunoglobulin-coated platelets by mononuclear macrophages) appears to be similar.

• Autoantibody stimulation
  • In persons with chronic immune thrombocytopenic purpura (ITP), membrane GPs on the surface of platelets become immunogenic, stimulating the production of platelet autoantibodies.
  • In persons with acute immune thrombocytopenic purpura (ITP), the stimulus for autoantibody production is also unknown. Platelet membrane cryptantigens may become exposed by the stress of infection, or pseudoantigens may be formed by the passive adsorption of pathogens on platelet surfaces.
• Autoantibody specificity
  • In persons with chronic immune thrombocytopenic purpura (ITP), approximately 75% of autoantibodies are directed against platelet GPIIb/IIIa or GPIb/IX GP complexes.
  • Presumably, the remaining 25% are directed against other membrane epitopes, including GPV, GPIa/IIa, or GPIV.
• Role of the spleen⁵
  • The spleen is the site of autoantibody production (white pulp).
  • It is also the site of phagocytosis of autoantibody-coated platelets (red pulp).
  • The slow passage of platelets through splenic sinusoids with a high local concentration of antibodies and Fc-gamma receptors on splenic macrophages lend to the uniqueness of the spleen as a site of platelet destruction.
  • Low-affinity macrophage receptors, Fc gamma RIIA, and Fc gamma RIIIA bind immune-complexed IgG and are the key mediators of platelet clearance.
• Platelet destruction
  • The mononuclear macrophage system of the spleen is responsible for removing platelets in immune thrombocytopenic purpura (ITP), because splenectomy results in prompt restoration of normal platelet counts in most patients with immune thrombocytopenic purpura (ITP).
  • Platelets are sequestered and destroyed by mononuclear macrophages, which are neither reticular nor endothelial in origin. Therefore, the former designation of reticuloendothelial system is considered imprecise.
  • Immune destruction of immunoglobulin-coated platelets is mediated by macrophage IgG Fc (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) and complement receptors (CR1, CR3).

Differential Diagnoses

Myelodysplastic Syndrome
Myelophthisic Anemia

Workup

Laboratory Studies

• Determination of complete blood cell (CBC) count
  • The hallmark of immune thrombocytopenic purpura (ITP) is isolated thrombocytopenia.
  • Anemia and/or neutropenia may indicate other diseases.
• Peripheral blood smear
  • The morphology of red blood cells (RBCs) and leukocytes is normal.
  • The morphology of platelets is typically normal, with varying numbers of large platelets. Some persons with acute immune thrombocytopenic purpura (ITP) may have megathrombocytes or stress platelets, reflecting the early release of megakaryocytic fragments into the circulation.
  • If most of the platelets are large, approximating the diameter of RBCs, or if they lack granules or have an abnormal color, consider an inherited platelet disorder.
  • Clumps of platelets on a peripheral smear prepared from ethylenediaminetetraacetic acid (EDTA)–anticoagulated blood are evidence of pseudothrombocytopenia.¹⁷ The diagnosis of this type of pseudothrombocytopenia is established if the platelet count is normal when repeated on a sample from heparin-anticoagulated or citrate-anticoagulated blood.
• Test for antibodies to HIV
  • In patients who have risk factors for HIV infection, a blood sample should be tested with an enzyme immunoassay for anti-HIV.¹⁸
  • During the acute HIV retroviral syndrome, the results of the anti-HIV assay may be negative. In this situation, a polymerase chain reaction for HIV DNA is more reliable than the anti-HIV assay.
• Test for antiplatelet antibodies
  • Assays for platelet antigen–specific antibodies, platelet-associated immunoglobulin, or other antiplatelet antibodies are available in some medical centers and certain mail-in reference laboratories.
  • The reliability of the results of a platelet antibody test is highly specific to the laboratory used. A negative antiplatelet antibody assay result does not exclude the diagnosis of immune thrombocytopenic purpura (ITP).¹⁹ We do not recommend this test as part of the routine evaluation.
  • Testing for antiplatelet antibodies is not required to diagnose immune thrombocytopenic purpura (ITP).
• Test for antinuclear antibodies
  • In selected women, the medical history may suggest a chronic, recurrent, multisystemic illness with vague, generalized signs or symptoms, such as recurrent, multiple, painful, tender, or swollen joints.
  • In such cases, a negative antinuclear antibody (ANA) result is useful in diagnosing immune thrombocytopenic purpura (ITP) if the patient's thrombocytopenia becomes chronic and resistant to treatment.
• Direct antiglobulin test: If anemia and thrombocytopenia are present, a positive direct antiglobulin (Coombs) test result may help establish a diagnosis of Evans syndrome.
• Helicobacter pylori testing
  • Studies from Italy^20,21 and Japan^22,23 indicate that many persons with immune thrombocytopenic purpura (ITP) have H pylori gastric infections and that eradication of H pylori results in increased platelet counts.
  • In the United States and Spain, the prevalence of H pylori infections does not appear to be increased in persons with immune thrombocytopenic purpura (ITP), and eradication of H pylori has not increased platelet counts.^24,25
  • Therefore, routine testing for H pylori infections in adults and children with ITP is not recommended.

Imaging Studies

• Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are relatively benign and useful noninvasive imaging studies that can be used to rule out other causes of thrombocytopenia. However, they are not part of the routine evaluation of patients who may have immune thrombocytopenic purpura (ITP).
• Promptly perform CT scanning or MRI when the medical history or physical findings suggest serious internal bleeding.

Procedures

• The primary diagnostic evaluation is bone marrow aspiration and biopsy. Patients with immune thrombocytopenic purpura (ITP) have a normal-to-increased number of megakaryocytes in the absence of other significant abnormalities. The value of bone marrow evaluation for a diagnosis of immune thrombocytopenic purpura (ITP) is unresolved, and more data are needed to establish clear guidelines.²⁶
• In adults who are thrombocytopenic and older than 60 years, we examine the bone marrow to exclude myelodysplastic syndrome or leukemia.
• In adults whose treatment includes corticosteroids, baseline pretreatment bone marrow aspiration may be useful for future reference. Many adults have treatment-resistant chronic immune thrombocytopenic purpura (ITP) evident after 3-6 months of treatment, and an alternative diagnosis may be pursued vigorously at that time. Marrow aspirate obtained before any steroid-induced changes may have occurred can be useful.
• Perform bone marrow aspiration and biopsy to evaluate for possible hypoplasia or fibrosis before splenectomy is performed.
• In children, bone marrow examination is not required for the diagnosis of acute immune thrombocytopenic purpura (ITP), except in those with atypical hematologic findings, such as immature cells on the peripheral smear or persistent neutropenia.²⁷  Many children with acute immune thrombocytopenic purpura (ITP) have an increased number of normal or atypical lymphocytes on the peripheral smear, reflecting a recent viral illness. Unresponsiveness to standard treatment after 6 months is an indication for bone marrow aspiration.

Histologic Findings

Bone marrow aspirate

The cellularity of the aspirate and the morphology of erythroid and myeloid precursors should be normal. The number of megakaryocytes may be increased. Because the peripheral destruction of platelets is increased, megakaryocytes may be large and immature, although in many cases the megakaryocyte morphology is normal. Older patients require a careful examination of megakaryocyte morphology to exclude an early myelodysplastic syndrome.

Bone marrow biopsy

Sections of a needle biopsy specimen or marrow clot should reveal normal marrow cellularity, without evidence of hypoplasia or increased fibrosis.

Splenic evaluation

The spleen reveals no specific findings. In adults, the microscopic finding of extramedullary hematopoiesis is atypical and indicates myeloid metaplasia. Carefully examine spleens removed from patients with immune thrombocytopenic purpura (ITP) for a primary splenic lymphoma or granuloma or other signs of an undiagnosed infectious disease.

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. Immune thrombocytopenic purpura (ITP) has no cure, and relapses may occur years after seemingly successful medical or surgical management.²⁸
• Corticosteroids (ie, oral prednisone, IV methylprednisolone) or high-dose dexamethasone^29,30,31 are the drugs of choice (DOCs) for the initial management of immune thrombocytopenic purpura (ITP). Treatment with corticosteroids may change marrow morphology. Therefore, bone marrow aspiration should be performed to confirm the diagnosis if the clinical presentation or other findings are atypical for acute immune thrombocytopenic purpura (ITP) before the patient is treated with corticosteroids.
• IV immunoglobulin (IVIG) has been the drug of second choice (after corticosteroids) for many years.^32,33 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.^34,35
• 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 intravascular hemolysis³⁶ and renal failure³⁷ have been reported.
• Most children with acute immune thrombocytopenic purpura (ITP) do not require treatment, and thrombocytopenia resolves spontaneously.^38,39
• If bone marrow aspiration is unacceptable to parents and if the diagnosis of acute immune thrombocytopenic purpura (ITP) is equivocal, IV RhIG is an effective treatment for immune thrombocytopenic purpura (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 immune thrombocytopenic purpura (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.
  • 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 immune thrombocytopenic purpura (ITP).
  • Adults whose platelet counts are greater than (50 X 10⁹/L (>50 X 10³/µL) 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 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.⁴⁰
  • If the platelet count is greater than 50 X 10⁹/L (>50 X 10³/µL), 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/µL) before delivery, treatment with oral prednisone and IVIG is recommended.
  • The standard dose of IV RhIG for immune thrombocytopenic purpura (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.⁴¹
• Among the treatment options after corticosteroids, IV RhIG, IVIG, and rituximab are 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.^{42,43,44,45,46,47}

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.
• Laparoscopic splenectomy is an interventional approach less invasive than traditional splenectomy and offers the promise of decreased postoperative morbidity and shorter recovery.^48,49  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 bacteria^50,51,52 and Babesia.⁵³
  • 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.
• 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.⁵⁴
• 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.^55,56
  • 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/µL), splenectomy becomes an option.
• Early consultation with a surgeon is useful for planning management.^57,58
• If the platelet count is less than 10 X 10⁹/L (<10 X 10³/µL) 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.⁵⁹ 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/µL] 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/µL), whichever occurs first. In critical situations, an IV infusion of a corticosteroid may be preferable.

Second-line (maintenance) treatment is IV RhIG 75/µg/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).⁶⁰
 
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 immune thrombocytopenic purpura (ITP) are available. 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 acute immune thrombocytopenic purpura (ITP)
 
For initial (induction) treatment (platelet count <20 X 10⁹/L [<20 X 10³/µL]), one regimen is prednisone 1.0 mg/kg/d with the intent of a rapid and complete taper in 7-10 days or as soon as possible thereafter.
 
For second-line treatment, the present authors recommend IV RhIG or IVIG. For third line, a trial of rituximab can be administered as described for children above.⁶¹ If the initial response to corticosteroids, IV RhIG, or IVIG is less than satisfactory in newly diagnosed acute immune thrombocytopenic purpura (ITP), the diagnosis of acute immune thrombocytopenic purpura (ITP) should be reevaluated. The possibility of an atypical presentation of a myelodysplastic syndrome or aleukemic leukemia should be pursued with flow cytometric and cytogenetic studies.

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.

No universally effective treatments are available for adults whose immune thrombocytopenic purpura (ITP) has persisted for at least 6 months (chronic immune thrombocytopenic purpura [ITP]), 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.⁶² 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.

Investigational new drugs

Most current 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.^63,64

Romiplostim (formerly AMG531) was approved by the US Food and Drug Administration 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.^65,66,67 Also, 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 has also been approved by the FDA in 2008.^68,69

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.

Dosing

Adult

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)

Interactions

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

Contraindications

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

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.

Dosing

Adult

1 g/d IV

Pediatric

30 mg/kg/d IV

Interactions

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

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

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.

Dosing

Adult

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

Interactions

None reported

Contraindications

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 D-positive or unknown

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.

Dosing

Adult

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

Interactions

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

Contraindications

Documented hypersensitivity; IgA deficiency; anti–IgE/IgG antibodies

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.

Dosing

Adult

2 mg/kg/d PO/IV

Pediatric

Not established

Interactions

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

Contraindications

Documented hypersensitivity

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.

Dosing

Adult

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

Interactions

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

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

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.

Dosing

Adult

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

Pediatric

Not established

Interactions

Decreases insulin requirements and increases the effects of anticoagulants

Contraindications

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

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.

Dosing

Adult

375 mg/m² IV infusion qwk for 4 doses

Pediatric

Not established

Interactions

Decreases circulating B lymphocytes

Contraindications

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

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.

Thrombopoietic Agent

These thrombopoietic agonists directly stimulates bone marrow platelet production.⁶⁶

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).

Dosing

Adult

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

Interactions

None reported; data limited

Contraindications

None known

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).

Dosing

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

Pediatric

Not established

Interactions

CYP1A2, CYP2C8, UGT1A1, and UGT1A3 substrate; OATP1B1 inhibitor; UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 inhibitor
Coadministration with moderate or strong CYP1A2 (eg, ciprofloxacin, fluvoxamine) or CYP2C8 (eg, gemfibrozil, trimethoprim) inhibitors may inhibit eltrombopag's oxidative metabolism and increase toxicity
Coadministration with UGT1A1 or UGT1A3 inhibitors or inducers may affect glucuronidation of eltrombopag
Inhibits OATP1B1 and may increase exposure to OATP1B1 substrates (eg, benzylpenicillin, atorvastatin, fluvastatin, pravastatin, rosuvastatin, methotrexate, nateglinide, repaglinide, rifampin)
Inhibits UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 enzymes and therefore may increase systemic exposure of substrates (eg, acetaminophen, narcotics, NSAID)
Chelates polyvalent cations; allow 4-h interval for administration of other medications, calcium-rich foods, or supplements containing polyvalent cations (eg, antacids, aluminum, calcium, iron, magnesium, selenium, zinc)

Contraindications

None known

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 cause hepatic impairment, monitor ALT, AST, and bilirubin, and discontinue if levels increase; may cause bone marrow fibrosis because of reticulin fiber deposition; excessive dose may increase platelet counts and produce thrombotic/thromboembolic complications (discontinue if platelet count >400 X 10⁹/L after 2 wk at lowest dose); may increase risk for hematological malignancies; monitor CBC count weekly during dose adjustment, monthly following stable dose, and at least 4 wk after discontinuation

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 º C or 102 º F) should receive IV antibiotics until bacterial infection is excluded.

Prognosis

• Children
  • More than 80% of children with untreated immune thrombocytopenic purpura (ITP) have a spontaneous recovery with completely normal platelet counts in 2-8 weeks.
  • Fatal bleeding occurs in 0.9% upon initial presentation.
  • 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.
  • Data on this subject are difficult to locate.
  • Fatal intracerebral hemorrhage occurs rarely in children who have been treated with prednisone and IV RhIG or IVIG for at least 2 days.
• Adults
  • 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.
  • 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.⁷⁰

Miscellaneous

Medicolegal Pitfalls

• Permanent neurologic damage
  • Although nondefinitive, the guidelines for the risk of a serious hemorrhage that complicates immune thrombocytopenic purpura (ITP) should be followed.
  • 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
  • IV RhIG and IVIG are manufactured from pooled human plasma.
  • 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
  • Management of immune thrombocytopenic purpura (ITP) that develops during pregnancy requires the close cooperation of the patient, the obstetrician, and the hematologist.
  • Most pharmaceuticals used in the treatment of immune thrombocytopenic purpura (ITP) are not categorized for use during pregnancy.
  • Obtaining informed consent is essential.
  • Emphasize to the mother the importance of fetal health and the risk of fetal intracranial bleeding with maternal immune thrombocytopenic purpura (ITP).

Multimedia

Media file 1: Peripheral blood smear from a patient with immune thrombocytopenic purpura (ITP) illustrates a decreased number of platelets, a normal-appearing neutrophil, and erythrocytes. ITP is diagnosed by excluding other diseases; therefore, the absence of other findings from the peripheral smear is at least as important as the findings are observed. This smear demonstrates the absence of immature leukocytes (as in leukemia) and fragmented erythrocytes (as in thrombotic thrombocytopenic purpura) and no clumps of platelets (as in pseudothrombocytopenia).

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Keywords

immune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, ITP, autoimmune thrombocytopenic purpura, primary thrombocytopenic purpura, thrombocytopenia, purpura, petechiae, thrombocytopenic purpura, bleeding disorder, platelet disorder, splenectomy, intravenous immune globulin therapy, IVIG therapy, IV RhIG therapy, intravenous RhIG therapy, intravenous Rho immune globulin therapy

Contributor Information and Disclosures

Author

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, International Society of Blood Transfusions, and Medical Society of the District of Columbia
Disclosure: Nothing to disclose.

Coauthor(s)

Rumina Bhanji, MD, Staff Physician, Departments of Pathology and Laboratory Medicine, Georgetown University Hospital
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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 Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

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, Kimmel Cancer Center, 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 Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Related eMedicine Topics

• Idiopathic Thrombocytopenic Purpura
• Immune Thrombocytopenia and Pregnancy
• Thrombocytopenia in Pregnancy

Clinical Trial

• A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP

Clinical Guideline

• Thrombocytopenia. Finnish Medical Society Duodecim - Professional Association. 2001 Apr 30 (revised 2007 Apr 27). Various pagings. NGC:005827

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