ACUTE AND CHRONIC IDIOPATHIC (IMMUNE) THROMBOCYTOPENIC PURPURA

Acute ITP is a reduction in platelets that most commonly occurs in children, is associated with an antecedent viral infection, and is transient. This condition does occasionally occur in adults. Commonly associated viral illnesses include upper respiratory tract illnesses, varicella, rubella, rubeola, cytomegalovirus, and Epstein-Barr virus. This condition has also been associated with vaccinations for measles or smallpox. Rapid platelet destruction in this condition is the result of IgG and IgM autoantibody-mediated platelet destruction, which is directed against platelet-associated antigen. Platelet destruction occurs primarily within the spleen but also within the liver. Aplastic anemia and acute leukemia must be excluded as causes of the thrombocytopenia.

Clinically, children between the ages of 2 and 9 years present with generalized purpura, hemorrhagic mucosal bullae, diffuse petechiae, or hemorrhaging from the nares or gums. Consistent laboratory findings include platelet counts less than 20,000 cells/mm3, anemia, eosinophilia, and lymphocytosis. An increased number of megakaryocytes on bone marrow examination is consistent with this disorder whereas a decreased bone marrow megakaryocyte count would be consistent with leukemia. However, some authorities believe routine bone marrow biopsy is unnecessary.

Treatment of this disorder is supportive unless evidence of acute life-threatening bleeding or platelet counts less than 20,000 cells/mm3 exist. If severe hemorrhaging is ongoing, platelet transfusion is indicated. If the patient is asymptomatic and the platelet count is less than 20,000 cells/mm3, then prednisone 1-2 mg/kg per day is instituted for 2 weeks or IVIG 400 mg/kg per day for 5 days. Supportive care consists of counseling the patient and family that the condition is generally benign and transient, instructing the patient to avoid medications which alter platelet activity (i.e., aspirin or NSAIDs) and restriction of physical activity to minimize trauma until the condition has resolved.

Chronic ITP is characterized by persistent thrombocytopenia for 6 months or more, and is an autoimmune process directed against antibody-coated or immune complex-coated platelets with increased peripheral platelet destruction. This disorder is seen primarily in adult women of childbearing age and is not associated with splenomegaly. Chronic ITP is commonly seen in persons afflicted with HIV, and persons diagnosed with ITP should undergo HIV testing.

Clinical manifestations of chronic ITP include ecchymosis, petechiae, epistaxis, or menorrhagia. Intracranial hemorrhage represents a life-threatening complication and occurs in 2 to 6% of cases. However, the majority of these patients do not appear ill other than by having an increased bruising tendency. Common laboratory abnormalities include thrombocytopenia with large immature platelets noted on peripheral smear exam, and an increase in megakaryocyte numbers and volume on bone marrow examination. Antiplatelet antibodies are detected in 90% of patients; however, this finding is nonspecific.

As mentioned, an increased incidence of chronic ITP exists in HIV-infected persons. In fact, 15 to 20% of persons with HIV manifest ITP. Investigators from France have suggested that a common epitope exists on both the HIV and platelets so there is a cross-reaction with resultant platelet destruction. Also, HIV may directly infect megakaryocytes resulting in impaired platelet production in HIV-infected patients as opposed to the increased peripheral platelet destruction associated with ITP.

ITP is diagnosed after other potential etiologies have been excluded including collagen vascular disorders, lymphoproliferative disorders, agammaglobulinemia, alloimmune thrombocytopenia, congenital or hereditary thrombocytopenia, myelodysplasia, von Willebrand disease type IIB, infectious causes of thrombocytopenia, and medications associated with thrombocytopenia.*

The disease course may be variable with some patients having mild thrombocytopenia without progression and others having a more rapid or severe decrease in platelets. Those with stable, mild, and asymptomatic disease can be followed clinically without intervention.  The acceptable level of thrombocytopenia varies among active (platelets > 50, 000) and sedentary (platelets > 30,000) patients.

Emergently, hospitalization and therapy with IVIg (1 g/kg/day for two days), intravenous methylprednisolone 1 g/day for three days, and platelet transfusions may be required. Failing the previous mentioned treatments, aminocaproic acid (5 g bolus the 1 g every 5 hours PO or IV) may be given, and in severe cases, plasmapharesis be required. In nonemergent cases, prednisone or anti-Rh immunoglobulin may prove sufficient with the latter being effective in only Rh-D-positive nonsplenectomized patients. Screening for infection with Helicobacter pylori and eradication if present may prove effective in some patients although response rates are variable.  If symptoms do not respond to therapy then treatment options include splenectomy or weekly subcutaneous injections of romiplostim (3 microg/kg and titrate up to 10 microg/kg to a target platelet level of 50-200 cells/mm3). Other treatment options include danazol 200 mg PO TID, cyclophosphamide, vincristine, Cyclosporin A, Rituximab, Campath-1H, or stem cell transplantation. Consultation with a hematologist may be prudent.