> Table of Contents > Immune Thrombocytopenia (ITP)
Immune Thrombocytopenia (ITP)
William A. Stevens, MD
Khalid A. Jaboori, MD, MPH
image BASICS
DESCRIPTION
  • 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
EPIDEMIOLOGY
  • 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)
Incidence
  • Pediatric acute ITP: 1.9 to 6.4/100,000 children/year (1)
  • Adult ITP: 3.3/100,000 per year
Prevalence
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
ETIOLOGY AND PATHOPHYSIOLOGY
  • 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.
RISK FACTORS
  • 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
COMMONLY ASSOCIATED CONDITIONS
  • 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
image DIAGNOSIS
A careful history, physical exam, and review of CBC and peripheral blood smear remain the key components of the diagnosis of ITP.
PHYSICAL EXAM
  • 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
DIFFERENTIAL DIAGNOSIS
  • 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
DIAGNOSTIC TESTS & INTERPRETATION
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.
image TREATMENT
GENERAL MEASURES
  • 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.
MEDICATION
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].
  • EMERGENCY TREATMENT
    • 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.
ISSUES FOR REFERRAL
Hematology consultation is recommended for acute bleeding or for those who fail to respond to first-line therapies.
ADDITIONAL 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).
SURGERY/OTHER PROCEDURES
Splenectomy
  • 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].
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Platelet counts weekly for patients on prednisone and monthly for stable patients are reasonable.
DIET
  • 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.
PATIENT EDUCATION
  • Modified activity to prevent injury or bruising; avoid contact sports.
  • Avoid anticoagulants, aspirin and other plateletinhibiting drugs, and NSAIDs.
PROGNOSIS
  • 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).
REFERENCES
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.
Codes
&NA;
ICD10
D69.3 Immune thrombocytopenic purpura
Clinical Pearls
&NA;
  • 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