Immune thrombocytopenia (ITP), previously known as idiopathic thrombocytopenic purpura, is defined as isolated thrombocytopenia with normal bone marrow and in the absence of other causes of thrombocytopenia. ITP has two distinct clinical syndromes, manifesting as an acute condition in children and a chronic condition in adults.
Isolated thrombocytopenia on a complete blood cell count (CBC) is the key laboratory finding (see Workup). Treatment depends on patient characteristics and clinical circumstances and ranges from observation only to pharmacologic therapy to splenectomy (see Treatment and Medication).
ITP is primarily a disease of increased peripheral platelet destruction, with most patients having antibodies to specific platelet membrane glycoproteins. Relative marrow failure may contribute to this condition, since studies show that most patients have either normal or diminished platelet production.
Acute ITP often follows an acute infection and has a spontaneous resolution within 2 months. Chronic ITP persists longer than 6 months without a specific cause.
ITP develops when platelets become coated with immunoglobulin G (IgG) 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 number of circulating platelets.
United States
Incidence rates are as follows:
International
According to studies in Denmark and England, childhood ITP occurs in approximately 10-40 cases per 1,000,000 per year.[1] A prospective, population-based study in Norway indicated an incidence of 53 per 1,000,000 in children younger than 15 years.[2] A study in Kuwait reported a higher incidence of 125 cases per 1,000,000 per year.
Hemorrhage represents the most serious complication; intracranial hemorrhage is the most significant. The mortality rate from hemorrhage is approximately 1% in children and 5% in adults. In patients with severe thrombocytopenia, predicted 5-year mortality rates from bleeding are significantly raised in patients older than 60 years versus patients younger than 40 years, 47.8% versus 2.2%, respectively. Older age and previous history of hemorrhage increase the risk of severe bleeding in adult ITP.
Spontaneous remission occurs in more than 80% of cases in children. However, it is uncommon in adults.
In acute ITP (children), distribution is essentially equal between males (52%) and females (48%). In chronic ITP (adults), the female-to-male ratio is 2.6:1. More than 72% of patients older than 10 years are female.
In children, peak incidence is at ages 2-4 years. Approximately 40% of all patients are younger than 10 years. In adults, peak incidence is at ages 20-50 years.
Approximately 83% of children have a spontaneous remission, and 89% of children eventually recover. More than 50% recover within 4-8 weeks. Approximately 2% die.
Only 2% of adults have a spontaneous recovery; however, approximately 64% of adults eventually recover. Approximately 30% have chronic disease, and 5% die from hemorrhage.
Complications of immune thrombocytopenia and its treatment may include the following:
Instruct patients to return for follow-up in order to assess for a potentially reduced platelet count. Emphasize close outpatient follow-up care. Because of the increased risk of bleeding, instruct patients to avoid aspirin products.
For patient education information, seethe Thrombocytopenia Directory.
Focus on the symptoms of bleeding (eg, type, severity, duration) and on symptoms that may exclude other causes of thrombocytopenia. Elicit risk factors for HIV and systemic symptoms linked to other illnesses or to medications (eg, heparin, alcohol, quinidine/quinine, sulfonamides) that may cause thrombocytopenia.
Medications can be a common etiology for inducing thrombocytopenia, and patients should have their medications carefully reviewed. One study used three distinct methods to document drugs that may be associated with drug-induced immune thrombocytopenia (DITP).[3, 4] Approximately 1500 drugs are associated with thrombocytopenia, but, using this analysis, 24 drugs had evidence of causing thrombocytopenia by all three methods.
Address risk factors for increased bleeding, such as GI disease, CNS disease, urologic disease, or active lifestyle, as these may determine the aggressiveness of management.
Onset of childhood ITP is typically abrupt, and often occurs several weeks after viral illness or live virus immunization. In adults, onset is typically gradual. Common signs include the following:
Limited data are available on the recurrent form of the disease. One study showed a 6% prevalence of recurrent ITP with most patients (69%) having only one recurrence. Though one third of patients had their recurrent episode within 3 months of their initial one, the remainder of patients had at least a 3-month interval between episodes.
Evaluate the type and the severity of bleeding and try to exclude other causes of bleeding. Seek evidence of liver disease, thrombosis, autoimmune diseases (eg, nephritis, cutaneous vasculitis, arthritis), and infection, particularly HIV.
Common physical findings include the following:
Isolated thrombocytopenia on a complete blood cell count (CBC) is the key laboratory finding. The white blood cell (WBC) count and hemoglobin level typically are normal, unless severe hemorrhage has occurred. On peripheral smear, truly giant platelets suggest congenital thrombocytopenia. Coagulation study results are normal, and a bleeding time is not useful.
A CT scan of the head is warranted if concern exists regarding intracranial hemorrhage.
Prehospital care focuses on the ABCs (airway, breathing, circulation), which include providing oxygen if necessary, controlling severe hemorrhage, and initiating intravenous (IV) fluids to maintain hemodynamic stability. Airway control may be necessary for a large intracranial hemorrhage.
Emergency medical services providers should be aware of the potential for serious bleeding complications in patients with immune thrombocytopenia (ITP).
The patient with known ITP who has bleeding that poses a threat to life, limb, or sight requires treatment to improve hemostasis along with conventional critical care interventions. Intravenous immunoglobulin (IVIG), which has the most rapid onset of action, should be considered along with high-dose parenteral glucocorticoids. In patients who require a more rapid rise in their platelet count, case reports suggest that the following treatments may be useful[5] :
Platelet transfusion is indicated for controlling severe hemorrhage. Send a blood specimen to the lab for type and screen in case platelet transfusion is necessary. Platelet survival is increased if the platelets are transfused immediately after IVIG infusion. A consultation with a hematologist may be required to make a decision regarding the transfusion of platelets.
Guidelines for transfusion dosage are as follows:
Splenectomy is reserved for patients in whom medical therapy fails. Fortunately, thrombopoietin receptor agonists can often provide effective second-line management of patients with persistently low platelet counts and bleeding, thus averting surgery.[6] When medical therapy fails in a patient with life-threatening bleeding, emergent splenectomy (with or without IVIG and/or corticosteroids and usually with platelet transfusions) may be considered as a heroic measure.[5]
In patients without life-threatening complications, focus ED care on confirming the diagnosis, if possible, and initiating therapy as needed. Most patients with undiagnosed thrombocytopenia and purpura will need admission for further evaluation and treatment, since ITP is a diagnosis of exclusion.
Transfer may be necessary under the following conditions:
Rule out other potential causes of thrombocytopenia. Emergency splenectomy may be necessary if severe bleeding complications due to thrombocytopenia do not respond to medical therapy. Observe for life-threatening bleeding. Consult with a hematologist, as further treatments (eg, steroids, IVIG, platelet transfusion) may be indicated.
Consult a hematologist for assistance in confirming the diagnosis or, in the patient with known ITP, arranging disposition and follow-up care, if appropriate.
Consult a neurosurgeon for intracranial hemorrhage. Consultation by other surgical specialists may be required for extensive hemorrhage at other sites.
American Society of Hematology (ASH) guidelines recommend that in children who have no bleeding, or only mild bleeding (ie, skin manifestations only, such as bruising and petechiae), regardless of the platelet count, management should be with observation alone. For pediatric patients requiring treatment, ASH suggests a short course of corticosteroids for first-line treatment rather than IVIG or anti-D immunoglobulin.[7]
For children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIG, RhIG, or conventional doses of corticosteroids, the ASH suggests a thrombopoietin receptor agonist (TPO-RA) rather than rituximab or splenectomy as second-line treatment. Rituximab may also be considered as an alternative to splenectomy.[7]
A 2010 international consensus report advised that treatment for ITP is rarely indicated in adult patients with platelet counts above 50×109/L, in the absence of the following[8] :
In adults, treatment is recommended for a platelet count < 30×109/L. The ASH recommends that if treatment is needed, shorter courses of corticosteroids (≤6 weeks) are preferred over prolonged courses (>6 weeks including treatment and taper) as first-line treatment. The guidelines suggest either prednisone (0.5-2.0 mg/kg per day) or dexamethasone (40 mg per day for 4 days) as the type of corticosteroid for initial therapy. [7]
In adults with ITP lasting ≥3 months who are corticosteroid-dependent or have no response to corticosteroids, the ASH guidelines suggest either splenectomy or a TPO-RA. In adults who are going to be treated with aTPO-RA, either eltrombopag or romiplostim is suggested by the ASH guidelines. ASH also suggests rituximab over splenectomy.[7]
For adults with ITP, ASH guidelines recommend treating newly diagnosed patients whose platelet count is less than 30 × 109/L. Recommendations for first-line treatment include the following[7, 5] :
Recommended second-line treatments for cases that do not respond to corticosteroids, or recur afterward, are as follows, in order of preference[7] :
Increasingly, clinicians are trying TPO-RAs before referring patients for splenectomy. According to published data, 25–30% of patients who are treated with TPO-RAs have a sustained response after stopping the drug. The mechanism for these sustained responses is not known. Spontaneous remission is unlikely as an explanation, as the patients in reported studies had all received several prior treatments and had severe, prolonged thrombocytopenia.[9]
Close follow-up care with a hematologist is required. Elective splenectomy may be necessary if medical therapy fails.
In 2019, the American Society of Hematology (ASH) published an update to their 2011 evidence-based practice guideline for immune thrombocytopenia (ITP). The 2019 guideline comprises strong recommendations and conditional recommendations/suggestions. Recommendations and suggestions are provided separately for pediatric and adult patients.[7] Some of the 2011 recommendations remained unchanged and were not included in the 2019 review and update.[5]
The 2011 ASH guidelines recommend that bone marrow examination is not necessary in children and adolescents with the typical features of ITP, or in children in whom intravenous immunoglobulin (IVIG) therapy fails. ASH suggestions are that bone marrow examination is not necessary in similar patients before initiation of treatment with corticosteroids or before splenectomy, and that testing for antinuclear antibodies is not necessary in the evaluation of children and adolescents with suspected ITP.[5]
ASH has moved away from recommending treatment on the basis of the platelet count. The 2019 ASH guidelines recommend that children with no bleeding or mild bleeding (ie, skin manifestations only, such as bruising and petechiae) be managed with observation alone regardless of platelet count.[7]
ASH suggestions include the following for children with non–life-threatening mucosal bleeding and/or diminished health-related quality of life (HRQoL)[7] :
The 2011 ASH guidelines recommend testing adult patients with ITP for hepatitis C virus and HIV. ASH suggests further investigations if the blood count or peripheral blood smear reveals abnormalities other than thrombocytopenia and perhaps findings of iron deficiency. ASH suggests that a bone marrow examination is not necessary irrespective of age in patients presenting with typical ITP.[5]
The 2019 ASH guidelines recommend against treatment of patients with a platelet count ≥30 × 109/L. For newly diagnosed patients with a platelet count < 30 × 109/L, guidelines suggest treatment with corticosterioids. For patients with a platelet count < 20 × 109/L, the guidelines suggest hospital admission for treatment. For first-line treatment, the guidelines further recommend a short course (≤6 weeks) of steroids over a prolonged course (> 6 weeks including treatment and taper) of steroids.[7]
Additional first-line treatment suggestions include the following[7] :
The following 2011 ASH guidelines treatment suggestions remain unchanged[5] :
If used, IVIG should be administered in a single dose of 1 g/kg; the dose may be repeated if necessary
Second-line treatment suggestions include the following[7] :
The 2011 ASH recommendation that for medically suitable patients laparoscopic and open splenectomy offer similar efficacy also remains unchanged.[5]
Glucocorticoids and intravenous immunoglobulin (IVIG) are the mainstays of medical therapy for immune thrombocytopenia (ITP). Indications for use, dosage, and route of administration are based on the patient's clinical condition, the absolute platelet count, and the degree of symptoms. Consultation with a hematologist may be needed prior to starting therapy.
In children with ITP who have no bleeding or mild bleeding (eg, cutaneous manifestations such as bruising and petechiae), the American Society of Hematology (ASH) recommends management with observation alone, regardless of the platelet count.[5] A retrospective review by Schultz et al found that this approach did not lead to an increase in later treatment or an increase in delayed bleeding symptoms.[10]
Adults with platelet counts > 50,000/mm3 do not require treatment. Treatment is indicated for adults with counts < 50,000/mm3 with significant mucous membrane bleeding. Treatment also is indicated for those adults with risk factors for bleeding (eg, hypertension, peptic ulcer disease, vigorous lifestyle) and in patients with a platelet count < 20,000-30,000/mm3.
IV Rho immunoglobulin (RhIG) is generally less toxic than IV steroids but is more expensive and has been associated with acute intravascular hemolysis, with an estimated incidence of one in 1115 patients. The ASH advises against the use of IV RhIG in splenectomized children, in those with a hemoglobin concentration that is decreased because of bleeding, or in those with evidence of autoimmune hemolysis. However, the ASH suggests that a single dose of IV RhIG can be used as first-line treatment in Rh-positive, nonsplenectomized children who require treatment.[5]
Steroid use and immunosuppressives and splenectomy may be undesirable because of their associated complications. For long-term steroid use, those include osteoporosis, glaucoma, cataracts, loss of muscle mass, and an increased risk of infection. For immunosuppressive therapy and splenectomy, risks include worsening immunosuppression and infection or sepsis.
Second-line options for treatment of ITP include rituximab and thrombopoietin receptor agonists (TPO-RAs). Rituximab has been used on its own as well as in combination with corticosteroids and in triple therapy with cyclosporine and dexamethasone.[11, 12, 13, 14]
The TPO-RAs eltrombopag and romiplostim are approved for use in patients with chronic ITP who have shown insufficient response to corticosteroids, immunoglobulins, or splenectomy.[15, 16] With both agents there are potential safety concerns such as thrombocytosis and rebound thrombocytopenia. It is unlikely that emergency physicians should be prescribing these agents without the recommendation of a hematologist.
Clinical Context: Useful in treating inflammatory and allergic reactions; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. DOC for all adult patients with platelet counts < 50,000/mm3. Asymptomatic patients with platelet counts >20,000/mm3, or patients with counts 30,000-50,000/mm3 with only minor purpura, may not need therapy; withholding medical therapy may be appropriate for asymptomatic patients, regardless of count.
Clinical Context: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased permeability. Used as alternative glucocorticoid of choice for all patients with severe, life-threatening bleeding or children with platelet counts < 30,000/mm3. Careful observation without medical treatment may be appropriate in some asymptomatic children.
Clinical Context: DOC for severe, life-threatening bleeding or for children with platelet counts < 20,000/mm3 with minor purpura; can be used alone or in addition to glucocorticoid therapy.
Clinical Context: 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 immune thrombocytopenia 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.
Clinical Context: 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 thrombocytopenia in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
