Case of the Week: ITP

Last week in Morning Report we discussed a case of a young woman referred to the AACU for isolated thrombocytopenia who we diagnosed with immune thrombocytopenic purpura (ITP). 

Learning Points

  1. Definition and Presentation of ITP
  2. Proposed Mechanism
  3. Differential Diagnosis of Thrombocytopenia
  4. Investigations
  5. When should I worry?
  6. Management

Definition and Presentation

Primary ITP is an acquired thrombocytopenia due to autoimmune platelet destruction, not triggered by an associated condition. Secondary ITP is ITP associated with another condition (e.g., HIV,  HCV, CLL, SLE).

Many patients (up to 1/3) are asymptomatic but others present with petechiae, dry or wet purpura, epistasxis or signs of more severe bleeding.

Proposed Mechanism of ITP

Multiple steps are involved in the proposed mechanism of ITP, including auto-antibody production and antibody-mediated destruction of platelets and impaired megakaryocyte platelet production.

 

Figure 1.
Figure 1. Proposed mechanism of immune dysregulation in ITP. (A) T cells are activated upon recognition of platelet-specific antigens on the APCs and therefore induce antigen-specific expansion of B cells. The B cells in turn produce autoantibodies with specificity for glycoproteins expressed on platelets and megakaryocytes. (B) Circulating platelets bound by autoantibody are removed by Fc receptors predominantly by splenic macrophages. (C) Autoantibodies also reduce the capacity of megakaryocytes to produce platelets. 

 

Source: Neunert C E Hematology 2013;2013 276-282

Differential Diagnosis of Thrombocytopenia

Remember to always rule out pseudothrombocytopenia (Secondary to EDTA-associated agglutinins, repeat in citrate tube)

DDx ITP

Note that for thrombocytopenia in pregnancy, in addition to non-pregnancy specific causes, there are pregnancy-specific causes including gestational thrombocytopenia (70-80%), severe preeclampsia (15-20%), HELLP syndrome (<1%), AFLP (<1%)

Investigations

  • CBC and differential
  • Blood film
  • HIV, Hepatitis C
  • PT/INR, aPTT (+/- fibrinogen if suspect DIC)
  • Vitamin B12 (+/- folate), LFTs
  • BhCG
  • Ancillary testing as appropriate:
    • H. pylori
      • As per ACG 2017 Guidelines on treatment of H. pylori, test only if intend to treat (grade 2C recommendation)
    • Quantitative Immunoglobulins
      • Look for CVID; immunosuppressive therapy is contraindicated in CVID; IVIG is contraindicated in IgA deficiency
    • DAT, IAT
    • APLA, ANA etc.

When should I worry?

  • Are there signs of clinically significant bleeding?
  • Is the patient septic?
  • Are there abnormal coagulation parameters? Consider DIC, APLA
  • Are other lineages affected? Rule out MAHA or a bone marrow process
  • Recent heparin? Consider HIT

Management

The majority of patients with platelets >30 and no bleeding or only skin manifestations (e.g., petechiae, bruising) can be treated with observation only

If your patient is not bleeding, but platelets are <30:

  • First line treatments: corticosteroids, IVIG or anti-D
    • Prednisone 1mg/kg daily (taper slowly after platelet count stabilizes after several weeks)
    • Dexamethasone 40mg daily x4 days
      • An RCT demonstrated higher initial and sustained response and better tolerance with dexamethasone compared to prednisone
    • IVIG 1g/kg x 2 days
      • Avoid in patients with IgA deficiency
      • Rare risk of aseptic meningitis
    • Anti-D 50-75 ug/kg
      • Only in Rh(D) +ve, unspelenctimized patients
      • Risk of severe hemolysis (use with caution)
  • Second line treatments: Rituximab, splenectomy, TPO receptor agonists (e.g., Romiplostim, Eltrombopag)

If your patient is actively bleeding:

  • Corticosteroids + transexamic acid. Consider IVIG but risk of hemolysis
  • If life threatening bleeding: platelet transfusion +/- splenectomy

If your patient is pregnant:

  • Remember to involve OB, anesthesia and pediatrics (neonatal thrombocytopenia)
  • Treat if clinically significant bleeding, plan for delivery or plt<30 and GA ≥36 weeks
  • Steroids (prednisone preferred over dex which crosses the placenta) or IVIG are first-line
  • Aim for plt >50 prior to delivery and for c-section and >80 for regional anesthetic (but check with anesthesia due to variation in local practices)

Additional Reading

  1. Cooper, N. (2017). State of the art–how I manage immune thrombocytopenia. British journal of haematology177(1), 39-54.
  2. Gernsheimer, T., James, A. H., & Stasi, R. (2013). How I treat thrombocytopenia in pregnancy. Blood121(1), 38-47.
  3. Neunert, C. E. (2013). Current management of immune thrombocytopenia. ASH Education Program Book2013(1), 276-282.
  4. Rajasekhar, A., Gernsheimer, T., Stasi, R., & James, A. H. (2013). Clinical practice guide on thrombocytopenia in pregnancy. Washington, DC: American Society of Hematology.
  5. Khan, A. M., Mydra, H., & Nevarez, A. (2017). Clinical practice updates in the management of immune thrombocytopenia. Pharmacy and Therapeutics, 42(12), 756.

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