AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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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 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 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 ITP; it is a diagnosis of exclusion.

Pathophysiology

An abnormal autoantibody, usually immunoglobulin G (IgG) with specificity for 1 or more platelet membrane glycoproteins (GPs), binds to circulating platelet membranes.

Autoantibody-coated platelets induce Fc receptor–mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen. The spleen is the key organ in the pathophysiology of 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.

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 chronic ITP is estimated to be 5.8-6.6 cases per 100,000 persons, but these data are not from large population-based studies. Most cases of acute ITP, particularly in children, are mild and self-limited and may not receive medical attention. Therefore, estimated incidences of acute ITP are difficult to determine and likely to understate the full extent of the disease.

Mortality/Morbidity

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

Sex

• In children, the prevalence is the same among boys and girls.
• In adults, women are affected approximately 3 times more frequently than men.

Age

• Children may be affected at any age, but the prevalence peaks in children aged 3-5 years.
• 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

Section 3 of 11  

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History

The medical history should focus on (1) factors that suggest another disease for which thrombocytopenia is a complication 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 erythematosus 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, ITP may manifest as a primary immune deficiency syndrome.
• Postviral illness
• • In children, most cases of 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 Ebstein-Barr virus, varicella virus, cytomegalovirus, rubella virus, or hepatitis virus (A, B, or C); thought the most typical association is a vaguely defined, viral, upper respiratory infection or gastroenteritis.
  • Transient thrombocytopenia often follows recent immunization with attenuated live-virus vaccines.
• HIV infection
• • Thrombocytopenia may occur during the acute retroviral syndrome coincident with fever, rash, and sore throat.
  • Thrombocytopenia may be a manifestation of 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.
  • 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, cephalothins, 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 also may 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. Prior 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
• • 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 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 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 distension may be evidence of hemopericardium.
• Abdomen
• • In children with acute ITP, the presence of a readily palpable spleen is not typical.
  • In an adult, hepatosplenomegaly is also atypical for ITP and may indicate chronic liver and other diseases. In fact, splenomegaly excludes the diagnosis of 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 ITP are acute, manifesting a few weeks after a viral illness. In adults, most cases of 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 ITP, membrane GPs on the surface of platelets become immunogenic, stimulating the production of platelet autoantibodies.
  • In persons with acute 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 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 spleen
• • 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 ITP because splenectomy results in prompt restoration of normal platelet counts in most patients with 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).

DIFFERENTIALS

Section 4 of 11  

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WORKUP

Section 5 of 11  

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Lab Studies

• Determination of CBC
• • The hallmark of ITP is isolated thrombocytopenia.
  • Anemia and/or neutropenia may indicate other diseases.
• Peripheral blood smear
• • The morphology of RBCs and leukocytes is normal.
  • The morphology of platelets is typically normal, with varying numbers of large platelets. Some persons with acute 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–anticoagulated blood are evidence of pseudothrombocytopenia. 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.
  • 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 ITP, and this test should not be considered part of the routine evaluation.
  • This test is not required to diagnose 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 result is useful in diagnosing 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 and Japan indicate that many persons with 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 ITP and eradication of H pylori has not increased platelet counts.
  • Therefore, routine testing for H pylori infections in adults and children with ITP is not recommended.

Imaging Studies

• CT scanning and 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 ITP.
• Promptly perform CT 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 ITP have a normal-to-increased number of megakaryocytes in the absence of other significant abnormalities.
• In adults who are thrombocytopenic and older than 60 years, 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 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 ITP, except in those with atypical hematologic findings, such as immature cells on the peripheral smear or persistent neutropenia. Many children with acute 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 ITP for a primary splenic lymphoma or granuloma or other signs of an undiagnosed infectious disease.

TREATMENT

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Medical Care

• The goal of medical care is to increase the platelet count to a safe level, permitting patients with 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.
• Corticosteroids (ie, oral prednisone, IV methylprednisolone) are the drugs of choice (DOCs) for the initial management of 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 ITP before the patient is treated with corticosteroids.
• IV immunoglobulin (IVIG) has been the drug of second choice (after corticosteroids) for many years. However, recent data indicate that, for Rh(D)-positive patients with ITP, IV Rho immunoglobulin (RhIG) offers comparable efficacy, less toxicity, greater ease of administration, and a lower cost than IVIG.
• The limitation of using IV RhIG is the lack of efficacy in Rh(D)-negative or splenectomized patients. Also, IV RhIG induces immune hemolysis in Rh(D)-positive persons and should not be used when the hemoglobin concentration is less than 8 g/dL.
• Most children with acute ITP do not require treatment, and thrombocytopenia resolves spontaneously.
• 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.
• • 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.
  • 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 ITP contains approximately 10-fold the concentration of anti-D that is in the standard antepartum dose of intramuscular RhIG for Rh immunoprophylaxis. While 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.
• 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.

Surgical Care

• In persons with acute ITP, splenectomy usually results in rapid, complete, and lifelong clinical remission.
• In persons with chronic ITP, the results of splenectomy are typically less predictable than they are in patients with acute 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. However, the ultimate role for laparoscopic splenectomy in 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.
• • 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.
• 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.
• • An accessory spleen is strongly indicated if Howell-Jolly bodies appeared on the peripheral smear after splenectomy and 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 or MRI.

Consultations

• Selecting a treatment program for 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.
• 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

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

Treatment plans

Given the goals and considerations mentioned above, treatment of acute ITP requires considerable individualization. The present authors recommend the general approach for children with acute 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/day with the intent of a rapid and complete taper after 7-10 days or when the platelet count is ¡Ý50 X 10⁹/L (¡Ý50 X 10³/µL), whichever occurs first.

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 platelet count is not maintained after 3-4 infusions, the patient might be refractory, and a different treatment should be considered. Conditions refractory to IV RhIG may respond to IVIG, and vice versa. If 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 recent 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).

The treatment of chronic, refractory 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 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 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. If the initial response to corticosteroids, IV RhIG, or IVIG is less than satisfactory in newly diagnosed acute ITP, the diagnosis of acute 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 ITP has persisted for at least 6 months (chronic 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 ITP may introduce risks of toxicity from medications that are comparable in severity to the risks of untreated thrombocytopenia. References provided in the Bibliography describe treatments with danazol, azathioprine, and cyclophosphamide. However, for patients with chronic refractory 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.

Drug Category: 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.

Drug Name	Methylprednisolone (Solu-Medrol)
Description	DOC for initial management of severe bleeding tendency in ITP. IV recommended when most rapid and reliable treatment of ITP 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.
Adult Dose	1 g/d IV
Pediatric Dose	30 mg/kg/d IV
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Interactions	Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Drug Category: Blood products

These products are used to improve clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.

Drug Name	IVIG (Gamimune, Gammagard, Sandoglobulin)
Description	Large dose of 1 g/kg induce 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 difference 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 supplement to corticosteroids, at least for Rh(D)-positive patients.
Adult Dose	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 Dose	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
Contraindications	Documented hypersensitivity; IgA deficiency; anti–immunoglobulin E (IgE)/IgG antibodies
Interactions	Increases toxicity of live-virus vaccine (measles, mumps, and rubella [MMR]); do not administer within 3 mo of vaccination
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in aseptic meningitis, renal insufficiency, and pulmonary insufficiency and thrombosis; acute reactions may include flushing, headaches, chills, nausea, or vomiting

Drug Category: Immunosuppressive antimetabolites

These agents are used in patients with ITP to reduce production of abnormal autoantibody.

Drug Category: Synthetic antineoplastic drugs

These drugs are chemically related to nitrogen mustards. They inhibit cell growth and proliferation.

Drug Category: Androgens

The steroidogenic properties of these drugs may modulate immune system.

Drug Category: Monoclonal antibodies

These are chimeric murine-human monoclonal antibody directed against CD20 on B lymphocytes.

FOLLOW-UP

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Complications

• Inform patients 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

• Children
• • More than 80% of children with untreated 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 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 require splenectomy, approximately two thirds have a sustained response and 10-15% have a partial response.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Permanent neurologic damage
• • Although nondefinitive, the guidelines for the risk of a serious hemorrhage complicating 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 ITP that develops during pregnancy requires the close cooperation of the patient, the obstetrician, and the hematologist.
  • Most pharmaceuticals used in the treatment of 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 ITP.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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).
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: May 30, 2006