Why is serum electrophoresis done in Immune Thrombocytopenic Purpura (ITP)?

Serum Electrophoresis in Immune Thrombocytopenic Purpura (ITP)

Serum electrophoresis is not routinely recommended in the standard diagnostic workup for ITP but may be performed to exclude secondary causes of thrombocytopenia, particularly to rule out paraproteins associated with lymphoproliferative disorders or autoimmune conditions that can mimic ITP. 1

Diagnostic Approach to ITP

ITP is fundamentally a diagnosis of exclusion that requires ruling out other causes of thrombocytopenia. According to the American Society of Hematology guidelines, the essential diagnostic tests for ITP include:

1. Complete blood count (CBC) with peripheral blood smear examination 1, 2
2. Examination of peripheral blood smear characteristics 1:
   • Normal-sized or slightly larger platelets (not giant platelets)
   • Normal red blood cell morphology
   • Normal white blood cell morphology

Peripheral Blood Smear Findings in ITP

• Consistent with ITP: Thrombocytopenia with normal-sized or slightly larger platelets, normal RBC and WBC morphology 1
• Not consistent with ITP: Red blood cell poikilocytosis, schistocytes, predominant giant platelets, or abnormal white cell morphology 1

Role of Serum Electrophoresis in ITP Diagnosis

While not explicitly mentioned as a routine test in the American Society of Hematology guidelines, serum electrophoresis may be performed for several reasons:

1. To exclude secondary causes of thrombocytopenia:

   • Paraproteins associated with lymphoproliferative disorders
   • Monoclonal gammopathies that can cause immune-mediated platelet destruction
   • Autoimmune conditions like systemic lupus erythematosus (SLE) that can present with secondary ITP 3

2. To differentiate primary ITP from secondary ITP:

   • Secondary ITP associated with SLE has different clinical characteristics and treatment responses compared to primary ITP 3
   • Patients with ITP associated with SLE typically have higher median platelet counts and fewer bleeding manifestations 3

Diagnostic Testing in ITP

The ASH guidelines list several tests for which the necessity/appropriateness is uncertain in ITP diagnosis 1:

For initial diagnosis in adults:

• ANA (antinuclear antibody)
• Direct antiglobulin test
• Lupus anticoagulant/antiphospholipid antibodies
• Chemistry profile
• Coagulation studies
• HIV testing
• Bone marrow examination

Before splenectomy:

• Antiphospholipid antibodies
• Abdominal CT/ultrasound
• Bone marrow examination (in some cases)

For refractory cases:

• More extensive immunological workup

Emerging Diagnostic Approaches

Recent research suggests additional tests that may aid in ITP diagnosis:

1. Ceruloplasmin measurement: A 2008 study found that serum ceruloplasmin levels were significantly higher in ITP patients compared to non-ITP thrombocytopenic patients, potentially offering diagnostic value 4

2. Immature platelet fraction (IPF): Typically elevated in ITP but can be low in some cases, complicating diagnosis 5

3. Glycoprotein-specific assays: Tests measuring antibodies against specific platelet glycoproteins (GP IIb/IIIa and GP Ib/IX) have shown improved specificity (91-92%) compared to traditional platelet-associated IgG assays (19%) 6

Practical Approach

When evaluating a patient with suspected ITP:

1. Start with CBC and peripheral blood smear examination
2. If clinical presentation and initial tests are consistent with ITP, consider targeted second-line testing based on clinical suspicion
3. Consider serum electrophoresis if:
   • Patient is older (>60 years)
   • There are symptoms or signs suggesting an underlying disorder
   • Patient has atypical features or poor response to standard therapy
   • There is suspicion for a paraprotein-related disorder

Pitfalls and Caveats

• ITP remains a diagnosis of exclusion without a definitive diagnostic test
• Bone marrow examination is not routinely needed but is indicated in specific circumstances, such as patients older than 60 years or those with systemic symptoms 2
• Pseudo-thrombocytopenia due to EDTA-dependent platelet agglutination should be excluded by obtaining platelet count in a non-EDTA tube 2
• Giant platelets on peripheral smear are not typical of ITP and may suggest an inherited thrombocytopenia 2