> Table of Contents > Immune Thrombocytopenia (ITP)
Immune Thrombocytopenia (ITP)
William A. Stevens, MD
Khalid A. Jaboori, MD, MPH
image BASICS
  • Immune thrombocytopenia (ITP) is a condition characterized by the immunologic destruction of platelets and/or impaired thrombopoeisis in response to an unknown stimulus.
  • ITP is classified by the following:
    • Age: adult or pediatric
    • Phases: newly diagnosed (<3 months), persistent, and chronic (>12 months)
    • Etiology: primary (idiopathic) or secondary when occurring in association with another disorder
  • ITP is a relatively common disease of childhood that typically follows a viral infection. Onset is within 1 week, and spontaneous resolution occurs within 2 months in 83% of patients.
  • In adults, ITP is usually a chronic disease and spontaneous remission is rare.
  • System(s) affected: heme, lymphatic, immunologic
  • Synonym(s): idiopathic thrombocytopenic purpura; immune thrombocytopenic purpura; and Werlhof disease
  • Peak age
    • Pediatric ITP: 2 to 4 years
    • Chronic ITP: >50 years with incidence two times higher in persons 60 years than those <60 years of age
  • Predominant gender
    • Pediatric ITP: male = female
    • Chronic ITP: female > male (1.2 to 1.7:1)
  • Pediatric acute ITP: 1.9 to 6.4/100,000 children/year (1)
  • Adult ITP: 3.3/100,000 per year
Limited data. In one population (in Oklahoma) (2):
  • Overall prevalence of 11.2/100,000 persons
  • In children (<16 years): 8.1/100,000 with average age of 6 years
  • In adults (> 16 years): 12.1/100,000 persons with average age of 55 years
  • Accelerated platelet uptake and destruction by reticuloendothelial phagocytes results from action of IgG autoantibodies against platelet membrane glycoproteins IIb/IIIa. There is also cell-mediated platelet destruction by CD8+ T cells.
  • Autoantibodies interfere with megakaryocyte maturation, resulting in decreased production.
  • Autoimmune thrombocytopenia (e.g., Evan syndrome)
  • Common variable immune deficiency
  • Drug side effect (e.g., quinidine, gold, penicillin, procainamide, methyldopa, sulfamethoxazole)
  • Infections: Helicobacter pylori, hepatitis C, HIV, CMV, and varicella zoster
  • Vaccination side effect
  • Bone marrow transplantation side effect
  • Connective tissue disease, such as systemic lupus erythematosus, antiphospholipid antibody syndrome
  • Lymphoproliferative disorders
  • Viral infections, such as measles, rubella, varicella, influenza, and EBV
  • Live virus vaccinations carry a lower risk than natural viral infection: 2.6/100,000 cases MMR vaccine doses versus 6 to 1,200/100,000 cases of natural rubella or measles infections
A careful history, physical exam, and review of CBC and peripheral blood smear remain the key components of the diagnosis of ITP.
  • Ecchymoses, petechiae, epistaxis, and bleeding from the gums are common.
  • Abnormal uterine bleeding may be present.
  • Hemorrhagic bullae on buccal mucosa reflect acute, severe thrombocytopenia.
  • Absence of splenomegaly, hepatomegaly, lymphadenopathy, stigmata of congenital disease
  • Acute leukemia
  • Thrombotic thrombocytopenic purpura
  • Hemolytic uremic syndrome
  • Factitious: platelet clumping on peripheral smear
  • Thrombocytopenia secondary to sepsis
  • Myelodysplastic syndrome, particularly in older patients
  • Decreased marrow production: malignancy, drugs, viruses, megaloblastic anemia
  • Posttransfusion
  • Gestational thrombocytopenia
  • Isoimmune neonatal purpura
  • Congenital thrombocytopenias
  • Disseminated intravascular coagulation
  • Alcohol-induced thrombocytopenic purpura
Initial Tests (lab, imaging)
  • CBC with differential and peripheral smear:
    • Isolated decreased platelet count <100 × 109/L
    • Giant platelets are usually present.
    • Normal red and white blood cell morphology
  • For patients with history, exam, CBC, and peripheral smear typical of ITP, consider the following:
    • PT/PTT is normal.
    • In adults, serologies for hepatitis B, hepatitis C, and HIV infections are recommended (3)[B].
    • In pediatric ITP, immunoglobulin levels to exclude common variable immunodeficiency are commonly obtained (3)[B].
    • Other tests are not necessary for patients with typical ITP presentation: antiplatelet, antinuclear, antiphospholipid antibodies; H. pylori testing; thrombopoietin; platelet parameters; direct antiglobulin test; reticulocyte count; urinalysis; and thyroid function tests (3)[C]
Diagnostic Procedures/Other
  • Imaging is not necessary.
  • Bone marrow aspiration/biopsy
    • Not necessary for diagnosis (pediatric (3)[B]; adult (3)[C])
    • Can be considered for a patient with atypical symptoms, such as fever and weight loss and multiple abnormalities in blood count
Test Interpretation
  • Peripheral smear: normal red and white cells with large or giant platelets but diminished in number
  • Marrow reveals abundant megakaryocytes with normal erythroid and myeloid precursors.
  • Management with observation alone in children with no or mild bruising or petechiae regardless of platelet count (3)
  • Outpatient management unless patient has platelet count <20 × 109/L and is at risk for bleeding (3).
  • Admit patients with active bleeding.
First Line
  • Pediatric
    • First-line treatment:
      • For children with no or mild bleeding (bruising and petechiae only with no mucosal bleeding), observation alone regardless of platelet count (3)[B]
      • For children with significant bleeding
        • Single-dose intravenous immunoglobulin (IVIG) 0.8 to 1 g/kg, especially when a more rapid increase in platelet count is desired (3)[B]. Do not administer in patients with IgA deficiencies because of anaphylaxis risk.
        • A short course of corticosteroids (e.g., PO prednisone 2 mg/kg/day for 2 weeks with 3 weeks taper) (3)[B]
        • For nonsplenectomized children who are Rh-positive, single dose of anti-Rho(D) immunoglobulin (anti-D), 50 to 75 g/kg. Do not use in children with low hemoglobin or evidence of hemolysis (3)[B].
    • Second and other treatments for pediatric and adolescent persons with ITP (3)
      • Splenectomy for chronic or persistent ITP (3)[B]
      • Rituximab (Rituxan) 375 mg/m2 weekly for 4 weeks (3)[C]
      • High-dose dexamethasone 0.6 mg/kg/day for 4 days every 4 weeks (3)[C]
      • Others without adequate data: azathioprine, cyclosporin A, danazol, mycophenolate mofetil, anti-CD52 monoclonal antibody, and interferon
  • P.545

  • Adult
    • First line, adult ITP
      • Treatment is recommended for newly diagnosed patients with platelet count <30 × 109/L (3)[C].
      • PO prednisone 1 to 2 mg/kg/day for 21 days then tapered (3)[B]
      • PO dexamethasone 40 mg daily for 4 days given every 2 to 4 weeks until platelets above 50 × 109/L (3)[B]
      • If corticosteroids are contraindicated:
        • IVIG: 1 to 2 g/kg once, repeating as necessary (3)[C]
        • OR anti-D: 50 to 75 &mgr;g/kg once, repeating as necessary for Rh+, nonsplenectomized patients. Do not use anti-D in patients with low hemoglobin or evidence of hemolysis (3)[C].
    • Second line, adult ITP
      • Splenectomy for patients who failed corticosteroid therapy (3)[B]
      • For patients whom splenectomy is contraindicated, thrombopoietin receptor agonists (3)[B]: eltrombopag (Promacta), 50 mg/day PO OR romiplostim (Nplate), 1 &mgr;g/kg SC weekly; may be used for patients at high risk of bleeding.
      • Rituximab: 375 mg/m2 IV weekly for 4 weeks, for patients at high risk of bleeding who have failed one line of therapy or post splenectomy (3)[C]
      • Consider combination therapy with dexamethasone and rituximab (4)[C].
      • Thrombopoietin receptor agonists can be considered for patients at risk of bleeding who failed first line of therapy (3)[C].
      • Others to consider: azathioprine, cyclosporine A, cyclophosphamide, danazol, dapsone, mycophenolate mofetil, and vincristine
  • ITP in pregnancy
    • Preeclampsia or gestational thrombocytopenia may cause thrombocytopenia unrelated to ITP.
    • Corticosteroids or IVIG are considered safe and are considered first line (4)[C].
    • DO NOT USE danazol or cyclophosphamide
    • ITP management at time of delivery is based on maternal bleeding risks, and mode of delivery should be based on obstetric indications (4)[C]. Platelet autoantibodies can cross the placenta and cause neonatal thrombocytopenia.
    • Caesarean section can be considered if platelet count >50 × 109/L.
    • Prednisone and/or IVIG may be considered 2 to 3 weeks prior to delivery.
  • ITP secondary to HIV
    • Antivirals should be considered before other treatment (3)[C].
    • If treatment is required, corticosteroids, IVIG, or anti-D are first-line options; and splenectomy is a second-line option (3)[C].
  • ITP secondary to HCV
    • Antivirals should be considered before other treatment (3)[C].
    • If treatment required, IVIG is initial treatment (3)[C].
    • Patients with intracranial or GI bleeding, massive hematuria, internal hematoma, or who need emergent surgery.
    • IV corticosteroids (e.g., IV methylprednisolone, 1 g/day for 3 doses (3)[B] with caution in patients with GI bleeding and/or IVIG 1 g/kg, repeat following day for count <50 × 109/L (3)[B].
    • Platelet transfusions with IVIG may also be considered for significant bleeding (3)[C].
    • Other agents that may be considered: Recombinant factor VIIa (3)[C] not only promotes hemostasis but also increases risk of thrombosis. Efficacy of antifibrinolytic agents, aminocaproic acids, and tranexamic acid, is unproved; they may be used as adjunctive treatments only. Emergent splenectomy has been reported.
Hematology consultation is recommended for acute bleeding or for those who fail to respond to first-line therapies.
Proprietary traditional Chinese medicines: Dihuang Zhixue (blend of Rehmannia root and others herbs) showed benefit for childhood refractory ITP in a single, small, randomized controlled trial (5); limited evidence for Kami-kihi-to, minor decoction of Bupleurum, replenishing qi and tonifying kidney, roasted licorice decoction, Sairei-to, Shengxueling, and Zhinu-I and Zhinu-II (6). Unclear evidence for active hexose correlated compound, berberine, dong quai, ginseng, licorice, melatonin, and periwinkle (7).
  • Mortality rate is very low (<1%) even in patients with severe thrombocytopenia.
  • Necessary vaccinations prior to splenectomy: polyvalent pneumococcal vaccine and quadrivalent meningococcal vaccine every 3 to 5 years and one-time Haemophilus influenzae B (Hib).
  • Consider lifelong prophylactic antibiotics with penicillin or erythromycin.
  • Should raise the platelet count to at least 20 × 109/L prior to surgery
  • Reported 5- to 10-year efficacy is ˜65% for all patients.
  • Laparoscopic splenectomy has similar long-term outcomes compared to open splenectomy and has better short-term outcomes (8)[C].
Patient Monitoring
Platelet counts weekly for patients on prednisone and monthly for stable patients are reasonable.
  • Evidence demonstrating benefit of an antiinflammatory diet in ITP is lacking.
  • The following foods and supplements can cause significant bleeding: garlic, ginger, Ginkgo biloba, and saw palmetto
  • Some foods and supplements that may inhibit platelets: evening primrose oil, fish oil, feverfew, ginseng, licorice, soy, vitamin C, vitamin E, and wintergreen
  • Partial list of foods and supplements with coumarin or salicylate components: alfalfa, angelica, anise, asafetida, aspen bark, birch, black cohosh, celery, chamomile, cinnamon, dandelion, fenugreek, heartsease, horse chestnut, meadowsweet, poplar, prickly ash, Quassia, sarsaparilla, sweet birch, sweet clover, and willow bark.
  • Modified activity to prevent injury or bruising; avoid contact sports.
  • Avoid anticoagulants, aspirin and other plateletinhibiting drugs, and NSAIDs.
  • Acute ITP
    • ˜80-85% of patients completely recover within 2 months.
    • 15% proceed to chronic ITP.
  • Chronic ITP
    • ˜10-20% of the patients recover spontaneously.
    • Remainder with diminished platelets for months to years
    • May see spontaneous remissions (5%) and relapses
  • ˜10% are refractory (fail medical therapy and splenectomy).
1. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol. 2010;85(3):174-180.
2. Terrell DR, Beebe LA, Neas BR, et al. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol. 2012;87(9):848-852.
3. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.
4. Gudbrandsdottir S, Birgens HS, Frederiksen H, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013;121(11):1976-1981.
5. Liu QC, Wu WH, Wu DY, et al. Clinical observation on the treatment of childhood refractory idiopathic thrombocytopenic purpura with Dihuang Zhixue Capsule. Chin J Integr Med. 2008;14(2):132-136.
6. Platelet Disorder Support Association. http://www.pdsa.org/. Accessed August 10, 2014.
7. Natural Standard. https://naturalmedicines.therapeuticresearch.com/databases.aspx. Accessed August 10, 2014.
8. Qu Y, Xu J, Jiao C, et al. Long-term outcomes of laparoscopic splenectomy versus open splenectomy for idiopathic thrombocytopenic purpura. Int Surg. 2014;99(3):286-290.
D69.3 Immune thrombocytopenic purpura
Clinical Pearls
  • ITP: platelet counts of <100 × 109/L caused by accelerated destruction and/or impaired thrombopoiesis by antiplatelet antibodies
  • Pediatric ITP: relatively common, with spontaneous remission in 2 months
  • Adult ITP: usually persistent; requires treatment, with rare spontaneous remission