Immune Throbocytopenia (ITP)

Background

Thrombocytopenia

Considered a platelet count <100-150k

  • Increased destruction - Generally platelets are large in size. Bone marrow is normal or has increased megakaryocytes
    • ITP
    • Neonatal alloimmune thrombocytopenia
    • Drug-induced thrombocytopenia (marrow suppression, drug-antibody immune complexes, drug-platelet reactions)
    • TTP/HUS - increased platelet activation, microthrombi and microangiopathic hemolytic anemia
    • DIC
    • Autoimmune diseases
    • Active infection - mononucleosis, CMV, parvovirus, varicella, hepatitis, HIV
  • Decreased production - Bone marrow demonstrates infiltration due to leukemia, storage disorders, myelofibrosis, granulomatous disorders
    • Hereditary amegakaryocytopoiesis - eg, Thrombocytopenia-Absent Radius Syndrome (TAR)
    • Congenital idiopathic amegakaryocytic thrombocytopenia
    • Bernard-Soulier - absence of GP1b, V, and IX
    • Wiskott-Aldrich - thrombocytopenia, eczema, immunodeficiency
  • Sequestration
    • Splenomegaly
    • Kasabach-Merritt syndrome -  Sequestration of platelets in hemangioma. Presents within weeks of birth.
      • Thrombocytopenia
      • Enlarging hemangioma
      • Microangiopathic anemia
  • Dilution - eg, after massive transfusions

Immune Thrombocytopenia (ITP)

Immune-mediated destruction of normal platelets most commonly in response to an unknown stimulus.

  • Children generally present between ages of 2-10years
  • Most children have spontaneous resolution within 6months, often within 6 weeks.
  • Pathophysiology: Autoantibodies are directed against platelet membrane antigens (GP IIb/IIIa), which are then cleared by the reticuloendothelial system.

Primary vs. Secondary

  • Primary ITP - Occurs in isolation
  • Secondary ITP
    • Autoimmune diseases, eg antiphospholipid antibody syndrome
    • Viral infections, eg. HIV, HCV, CMV, H.pylori, varicella, drugs

Acute vs. Chronic

  • Acute ITP is common in children  - Resolves by 6months
    • Thrombocytopenia
    • Purpuric rash
    • Normal bone marrow
  • Chronic ITP is more common among adolescents - Platelet < 150k for 6months

Workup- Diagnosis relies on history and physical as well as exclusion of other causes of thrombocytopenia. 

  • History: Epistaxis, excessive menstrual bleeding, mucocutaneous bleeding
    • Typically present with bruising/bleeding in an otherwise healthy child
    • 60% preport prior infection or MMR vaccination administration (rare).
    • Serious bleeding is uncommon.  Intracranial hemorrhage is the most worrisome but occurs in 0.1-0.5% of cases.
    • Family history, systemic symptoms, or recent use of certain drugs (heparin, quinidine, sulfonamides) should prompt evaluation of alternate diagnoses.
  • Physical exam
    • Cutaneous bleeding - Petechiae, purpura, ecchymoses (only symptom in 59% of cases)
    • Mucosal bleeding - Nasal, oral, genitourinary, gastrointestinal, lungs
    • Evidence of any systemic disease (lupus, RA, thyroid disease, or autoimmune hemolytic anemia), splenomegaly, lymphadenopathy, skeletal anomalies, fever, bone/joint pain, family history of low platelets or easy bruising, risk factors for HIV infection should prompt further evaluation of alternate diagnoses.
  • Labs
    • CBC with differential - Thrombocytopenia is the only abnormality.  Sometimes anemia can occur in children with significant bleeding.
    • Peripheral blood smear - Platelets are of normal to large in size. RBCs and WBCs are normal.
    • Neither testing for antinuclear, antiplatelet, and antiphospholipid antibodies nor performing a bone marrow biopsy is indicated for suspected ITP, unless an alternate diagnosis is suggested.

Disease course

  • 70% of cases are acute (<6months)
    • After 1mo, 92% have platelet counts > 20k
    • Complete remission (platelets >100k) 50% at 1month, 68% at 3 months, 75-80% at 6 months
  • 22-30% of cases are chronic (>6months)
    • Insidious onset, female patient, older age of onset, no history of recent illness

Treatment

  • Indications
    • Observation for pt with no bleeding or mild bleeding (cutaneous manifestations, eg petechiae and bruising) regardless of platelet count
    • Specific indications include severe life threatening bleeding, situations that increase risk of bleeding (surgery/dental work), any concomitant or preexisting bleeding disorder, poor follow-up, or anxiety or interference with daily activities from bleeding
  • Consideration
    • Goal is to achieve appropriate hemostasis, not a specific platelet level
    • 80% children recover with or without treatment within a few months
    • Most do not have any serious bleeding, even when platelets < 10k
    • Pharmacologic therapy does no significantly decrease risk of developing chronic ITP
  • Non-pharmacologic recommendations
    • Restrict activity that could cause bleeding, eg contact sports
    • Discontinue antiplatelet/anticoagulant medications
  • Pharmacologic intervention of acute ITP
    • Corticosteroids - First line treatment. Reduce antibody production, reduce reticuloendothelial system destruction of affected plaetelets, improve vascular integrity, decrease affinity of antibody for platelet, improve platelet production
      • Short course of corticosteroids is recommended
      • There is no evidence to support one dose, or dosing regimen, over others.  Long-term steroids should be avoided due to side effects.
    • IVIG - First line treatment. Most likely interferes with Fc receptor.  Prolongs survival of affected platelets
      • 0.8-1g/kg, single dose
      • Can be used if a more rapid increase in platelet count is desired
      • Side effect: Nausea, flu-like symptoms, fever
    • Anti-Rho (D) immunoglobulin - Works similarly to IVIG
      • Can be used as first-line in Rh+ non-splenectomized children
      • Side effect: Anemia.  Do not use in children with hemoglobin <10
  • Management of chronic ITP
    • Children < 10yo are likely to remit spontaneously
    • Children  >10yo, especially adolescent females, generally have courses closer to adults and are treated as such.
    • Indications for further treatment include persistent, significant bleeding despite first-line treatment and/or disruption of quality of life.  In general, intervention should be delayed for at least 12months.
      • If first-line treatment was successful, pt can receive this again especially during the first 12months.
      • Rituximab: For children or adolescents with significant, ongoing bleeding despite treatment
      • High-dose dexamethasone
      • Splenectomy
  • Pharmacologic intervention for life threatening bleeding
    • Platelet transfusion: Only if hemorrhage is life threatening
    • IVIG 1000mg/kg/day x 2days
    • High-dose corticosteroids: Methylprednisolong 30mg/kg/day IV x 3
  • Management of MMR-related ITP
    • Children with history of ITP who are not immunized should receive their scheduled first MMR vaccine.
    • In children with either non-vaccine or vaccine-related ITP who have already received their first dose of MMR vaccine, vaccine titers can be checked.  If immune, not further MMR vaccine is needed.  If not, re-immunize as scheduled.

References

  1. 2011 Clinical Practice Guideline on the Evaluation and Management of Immune Thrombocytopenia (ITP). American Society of Hematology.
  2. Consolini, Deborah M. Thrombocytopenia in infants and children. Pediatrics in Review 32.4 (2011): 135-151.
  3. Chu, Yu-Waye, James Korb, and Kathleen M. Sakamoto. Idiopathic thrombocytopenic purpura. Pediatrics in Review 21.3 (2000): 95-104.
  4. Kime, Courtney, et al. Patterns of Inpatient Care for Newly Diagnosed Immune Thrombocytopenia in US Children’s Hospitals. Pediatrics 131.5 (2013): 880-885.
  5. Neunert C. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood  2011 177:4190-4207.

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