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 thrombocytopenia (ITP).  *Please note that this post was written before the December 2019 ITP Guideline Update

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

By definition, the platelet count in typical ITP is <100 x 10⁹/L. 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.

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)

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 reticulocyte count
• Peripheral blood film
• HIV
• Hepatitis B and C
• PT/INR, aPTT (+/- fibrinogen if suspect DIC)
• Vitamin B12 (+/- folate), LFTs
• Pregnancy test in women of childbearing potential
• Quantitative Immunoglobulins
  • Look for CVID; immunosuppressive therapy is contraindicated in CVID; IVIG is contraindicated in IgA deficiency
• 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)
  • DAT, IAT
  • ANA
  • Antiphophoplipid antibodies
  • Antithyroid antibodies and thyroid function
  • Bone marrow examination (in selected patients)
  • Glycoprotein-specific antibody (difficult cases, poor sensitivity and not a primary diagnostic test)

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

Treatment must be individualized to the patient’s needs. 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 symptomatic and platelets are 30-50, often treatment will be considered.

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
    • Response rates 70-80% with corticosteroids
  • 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:
  • Update: ASH 2019 Guidelines
  • In adults with ITP lasting >3 months who are  corticosteroid-dependent or have no response to corticosteroids, the ASH
    guideline panel suggests either splenectomy (80% effective, up to 2/3rds have complete resolution), TPO receptor agonists) or a TPO-Receptor Agonists (TPO-RA e.g., Romiplostim, Eltrombopag)
  • TPO-RA are recommended over rituximab (60% response initially, 40% in long term),

If your patient is actively bleeding:

• Corticosteroids + transexamic acid. Consider IVIG but risk of hemolysis
• If life threatening bleeding: platelet transfusion +/- splenectomy
  • Note that platelet transfusion are contraindicated unless severe bleeding (ICH, GI Bleeding, for example)

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)

What is a Safe Platelet Count?

Note that platelet transfusion is not  needed for BM biopsy.

Additional Reading

1. Cooper, N. (2017). State of the art–how I manage immune thrombocytopenia. British journal of haematology, 177(1), 39-54.
2. Gernsheimer, T., James, A. H., & Stasi, R. (2013). How I treat thrombocytopenia in pregnancy. Blood, 121(1), 38-47.
3. Neunert, C. E. (2013). Current management of immune thrombocytopenia. ASH Education Program Book, 2013(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.