AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Idiopathic thrombocytopenic purpura (ITP), also known as primary immune thrombocytopenic purpura and autoimmune thrombocytopenic purpura, is defined as isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia. The 2 distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults.

ITP is a decrease in the number of circulating platelets in the absence of toxic exposure or a disease associated with a low platelet count.

Pathophysiology

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.

Frequency

United States

The incidence of ITP in adults is approximately 66 cases per 1,000,000 per year.

An average estimate of the incidence in children is 50 cases per 1,000,000 per year.

New cases of chronic refractory ITP comprise approximately 10 cases per 1,000,000 per year.

International

According to studies in Denmark and England, childhood ITP occurs in approximately 10-40 cases per 1,000,000 per year. A study in Kuwait reported a higher incidence of 125 cases per 1,000,000 per year.

Mortality/Morbidity

• 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 but is uncommon in adults.

Sex

• 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 acute ITP (children), distribution is equal between males (52%) and females (48%).

Age

• Peak prevalence occurs in adults aged 20-50 years.
• Peak prevalence occurs in children aged 2-4 years.
• Approximately 40% of all patients are younger than 10 years.

CLINICAL

Section 3 of 10  

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

History

• 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.
• 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.
• Common signs, symptoms, and precipitating factors include the following:
• • Abrupt onset (childhood ITP)
  • Gradual onset (adult ITP)
  • Purpura
  • Menorrhagia
  • Epistaxis
  • Gingival bleeding
  • Recent live virus immunization (childhood ITP)
  • Recent viral illness (childhood ITP)
  • Bruising tendency
• 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.

Physical

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:
• • Nonpalpable petechiae, which mostly occur in dependent regions
  • Hemorrhagic bullae on mucous membranes
  • Purpura
  • Gingival bleeding
  • Signs of GI bleeding
  • Menometrorrhagia, menorrhagia
  • Retinal hemorrhages
  • Evidence of intracranial hemorrhage, with possible neurologic symptoms
  • Nonpalpable spleen: The prevalence of palpable spleen in patients with ITP is approximately the same as that in the non-ITP population (ie, 3% in adults, 12% in children).
  • Spontaneous bleeding when platelet count is less than 20,000/mm³.

Causes

• Immunoglobulin G (IgG) autoantibodies on the platelet surface

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Pseudothrombocytopenia (platelet clumping in the presence of ethylenediaminetetraacetic acid [EDTA])
Liver disease
Myelodysplasia
Lymphoproliferative, autoimmune, or infectious diseases
Pregnancy-associated thrombocytopenia
Drug-induced immune thrombocytopenia (alcohol, heparin, quinine/quinidine, sulfonamides)
Infection/sepsis
Acute leukemia
Myelodysplastic syndrome
Malignancy
Megaloblastic anemia
Isoimmune neonatal purpura
Transfusion
Factitious

WORKUP

Section 5 of 10  

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

Lab Studies

• CBC
• • Isolated thrombocytopenia is the key finding regarding laboratory evaluation.
  • Truly giant platelets on peripheral smear suggest congenital thrombocytopenia.
  • The WBC count and hemoglobin typically are normal, unless severe hemorrhage has occurred.
• Coagulation studies are normal, and a bleeding time is not useful.

Imaging Studies

• A CT scan of the head is warranted if concern exists regarding intracranial hemorrhage.

TREATMENT

Section 6 of 10  

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

Prehospital Care

• Prehospital care focuses on the ABCs, which include providing oxygen, controlling severe hemorrhage, and initiating intravenous (IV) fluids to maintain hemodynamic stability.
• Prehospital airway control may be necessary for a large intracranial hemorrhage.
• EMS providers should be aware of the potential for serious bleeding complications in patients with idiopathic thrombocytopenic purpura (ITP).

Emergency Department Care

• Life-threatening bleeding requires conventional critical care interventions.
• In the patient with known ITP, high-dose parenteral glucocorticoids and IV immunoglobulin (IVIg), with or without platelet transfusions, are appropriate.
• 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
• • 6-8 U of platelet concentrate, or 1 U/10 kg
  • 1 U of platelets to increase count of a 70-kg adult by 5-10,000/mm³ and an 18-kg child by 20,000/mm³
• Splenectomy is reserved for patients in whom medical therapy fails. Emergent splenectomy is indicated in patients with life-threatening bleeding in whom medical therapy fails.
• 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.

Consultations

• 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.

MEDICATION

Section 7 of 10  

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

Glucocorticoids and IVIg are the mainstays of medical therapy. 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.

Children who have platelet counts >30,000/mm³ and are asymptomatic or have only minor purpura do not require routine treatment. Children who have platelet counts <20,000/mm³ and significant mucous membrane bleeding and those who have platelet counts <10,000/mm³ and minor purpura should receive specific treatment.

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 anti-(Rh)D, also known as IV Rh immune globulin (IG), was not recommended by the 1996 American Society of Hematology practice guidelines. However, recent studies using higher dosages of IV RhIG in acute ITP in children and adults show platelet count increases at 24 hours faster than medicating with steroids and at 72 hours similar to IVIg. Although generally less toxic than IV steroids, IV RhIG is more expensive than IV steroids. Studies in children with chronic ITP show that escalating or elevated doses of IV RhIG have comparable responses to those of high-dose IVIg therapy in children. This therapy is not appropriate for patients who have undergone splenectomy. Acute intravascular hemolysis after infusing IV RhIG has been reported, with an estimated incidence of 1 in 1115 patients.

Steroid use and immunosuppressives and splenectomy may be undesirable because of their associated complications. For long-term steroid use, this includes 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. Studies of the use of multiagent therapies in refractory patients are ongoing. Some small studies have shown limited success. According to one study¹, using a combination of weekly vincristine, weekly methylprednisolone, both until platelet counts reached 50,000/mm³, and cyclosporine orally twice daily until the platelet count is normal for 3-6 months seems promising, though larger prospective studies are needed.

Other therapies, such as cyclophosphamide, danazol, dapsone, interferon alfa, azathioprine, vinca alkaloids, accessory splenectomy, and splenic radiation have been studied. Many case series discussing these treatments are too small to show sufficient evidence of a clinically significant reduction in bleeding or mortality rate; however, they serve as additional therapeutic measures in ITP refractory-to-primary therapy (eg, glucocorticoids, IVIg immunoglobulin, splenectomy). Newer studies on rituximab suggest that this agent is an effective treatment option in splenectomized refractory or relapsed ITP patients.^{2, 3}

Clinical trials have shown promise for agents that directly stimulate platelet production, such as thrombopoietin (TPO) receptor-binding agents. While they show promise for raising platelet counts, there are potential safety concerns such as thrombocytosis and rebound thrombocytopenia.

Drug Category: Glucocorticoids

These agents are used to treat idiopathic and acquired autoimmune disorders. They have been shown to increase platelet count in ITP.

Drug Category: Blood products

Administration of IVIg may temporarily increase platelet counts in some children and adults with ITP. Consider IVIg if the situation requires a rapid, temporary rise in platelet count.

Drug Category: Thrombopoietic Agent

Romiplostim is the first product approved in the United States that directly stimulates bone marrow platelet production.⁴

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• 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.

Further Outpatient Care

• Close follow-up care with a hematologist is required.
• Elective splenectomy may be necessary if medical therapy fails.

Transfer

• Transfer may be necessary under the following conditions:
• • A hematologist is not available.
  • Blood bank support is insufficient.
  • A higher level of intensive care is needed.

Complications

• Complications of idiopathic thrombocytopenic purpura may include the following:
• • Intracranial or other major hemorrhage
  • Severe blood loss
  • Adverse effects of corticosteroids
  • Pneumococcal infections if the patient must have a splenectomy

Prognosis

• Children
• • Approximately 83% of children have a spontaneous remission, and 89% of children eventually recover.
  • More than 50% of patients recover within 4-8 weeks.
  • Approximately 2% of patients die.
• Adults
• • Only 2% of adults have a spontaneous recovery; however, approximately 64% of adults eventually recover.
  • Approximately 30% of patients have chronic disease, and 5% of patients die from hemorrhage.

Patient Education

• 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.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Failure to consider other causes of thrombocytopenia
• Failure to initiate therapy

Special Concerns

• Pregnancy
• • Gestational thrombocytopenia and thrombocytopenia due to preeclampsia are more common than ITP in pregnancy.
  • Pregnancy does not increase the incidence of ITP, and it does not exacerbate a preexisting disease.
  • The pregnant patient with ITP is treated the same as other patients with ITP.
  • Concerns about thrombocytopenia increase as term approaches, and the risks of thrombocytopenia to the newborn must be considered. This is because antiplatelet IgG antibodies can cross the placenta and can induce fetal thrombocytopenia. 
  • The perinatologist and the hematologist make the ultimate decisions regarding cesarean section (for protection of the newborn against intracranial hemorrhage), percutaneous umbilical blood sampling, prednisone, and IVIg therapy.
• Geriatrics: Patients older than 60 years may be at greater risk of severe bleeding than younger patients (<40 y) at equivalent platelet counts.

REFERENCES

Section 10 of 10

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

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Article Last Updated: Nov 13, 2008