What is the diagnostic approach for primary thrombocytopenia (low platelet count)?

Diagnosis of Primary Thrombocytopenia

Primary thrombocytopenia (ITP) is diagnosed by excluding other causes of low platelet count through a systematic approach of clinical evaluation, laboratory testing, and in some cases, bone marrow examination. 1

Initial Diagnostic Approach

Clinical Evaluation

• Thorough history assessment:

  • Bleeding manifestations (bruising, purpura, epistaxis, menorrhagia)
  • Medication use (prescription and non-prescription)
  • Alcohol consumption
  • Recent vaccinations or transfusions
  • Family history of bleeding disorders or thrombocytopenia
  • Constitutional symptoms (fever, weight loss)
  • Exposure to environmental toxins 1

• Physical examination:

  • Should be normal except for bleeding manifestations
  • Check for hepatomegaly, splenomegaly (moderate/massive splenomegaly suggests alternative diagnosis)
  • Assess for lymphadenopathy or signs of systemic disease 1
  • Evaluate for syndromic features that might suggest inherited disorders 1

First-Line Laboratory Testing

1. Complete blood count with peripheral smear examination

   • ITP shows isolated thrombocytopenia with otherwise normal CBC
   • Peripheral smear should show normal morphology of other cell lines
   • Evaluate for large or giant platelets 1
   • Rule out pseudothrombocytopenia due to EDTA-dependent platelet agglutination 1

2. Basic coagulation studies

   • Prothrombin time (PT)
   • Activated partial thromboplastin time (APTT)
   • Fibrinogen levels 1, 2

3. Von Willebrand factor screening

   • VWF antigen
   • Ristocetin cofactor activity
   • Factor VIII coagulant activity 1

Second-Line Diagnostic Testing

Infectious Disease Screening

• HIV testing (regardless of risk factors)
• Hepatitis C virus (HCV) testing
• Helicobacter pylori testing (urea breath test or stool antigen preferred)
  • Consider in adults where it may have clinical impact
  • Not routinely recommended in children except in high-prevalence areas 1

Immunologic Testing

• Antinuclear antibodies (ANA)
• Antiphospholipid antibodies including anticardiolipin antibody and lupus anticoagulant
• Serum immunoglobulins (IgG, IgA, IgM) 1, 2

Bone Marrow Examination

• Not routinely required for typical ITP cases

• Indicated in the following situations:

  • Patients older than 60 years
  • Presence of systemic symptoms or abnormal signs
  • Abnormalities in blood count/smear other than isolated thrombocytopenia
  • Before splenectomy is considered
  • Minimal or no response to first-line therapies
  • Unexplained bone pain 1

• When performed, should include:

  • Both aspirate and biopsy
  • Flow cytometry (especially to identify CLL)
  • Cytogenetic testing 1

Special Considerations

Children with Suspected ITP

• Diagnosis remains one of exclusion

• Children with atypical features should be referred to a pediatric hematologist

• Consider inherited thrombocytopenias if:

  • Thrombocytopenia present since early life
  • Positive family history
  • Characteristic features present 1

• Additional evaluations for persistent ITP (3-6 months):

  • Bone marrow examination if not previously done
  • Testing for infections (HIV/HCV/H. pylori)
  • Autoimmune markers
  • Immunoglobulin levels
  • Review of medication usage 1

Inherited Platelet Function Disorders

• Consider if there's a strong family history or syndromic features
• Evaluate using specialized tests:
  • Light transmission aggregometry (LTA)
  • Assessment of platelet granule release
  • Flow cytometry for major platelet surface glycoproteins 1

Common Pitfalls in Diagnosis

1. Failure to exclude pseudothrombocytopenia

   • Always confirm thrombocytopenia by collecting blood in a tube containing heparin or sodium citrate 3

2. Missing drug-induced thrombocytopenia

   • Comprehensive medication review is essential 1

3. Overlooking inherited thrombocytopenias

   • Consider genetic testing in cases with family history or congenital anomalies 1

4. Confusing ITP with thrombotic microangiopathies

   • Some conditions present with both thrombocytopenia and thrombosis (TTP, HIT, antiphospholipid syndrome) 3

5. Not recognizing pregnancy-associated thrombocytopenia

   • Differentiate between gestational thrombocytopenia, ITP, preeclampsia, and HELLP syndrome 2

Remember that primary ITP remains a diagnosis of exclusion, and the diagnostic approach should be systematic to rule out secondary causes of thrombocytopenia before establishing the diagnosis.