What is the approach to diagnosing and treating Harris syndrome in hematology?

Harris Syndrome in Hematology: Diagnosis and Management

Harris Platelet Syndrome (HPS) is a rare inherited giant platelet disorder characterized by thrombocytopenia, macroplatelets, and notably, an absence of bleeding manifestations despite low platelet counts.

Clinical Features and Epidemiology

• Originally described in healthy blood donors from India in the early 2000s, but now recognized in patients of non-Indian origin 1
• Characterized by:
  • Mild to severe thrombocytopenia
  • Presence of giant platelets (macroplatelets)
  • Absence of bleeding manifestations despite low platelet counts
  • No Döhle body inclusions in leukocytes (distinguishing it from MYH9-related disorders)

Diagnostic Approach

Laboratory Evaluation

1. Complete Blood Count (CBC):

   • Decreased platelet count: median 132 × 10^9/L (range 71-267) 2
   • Increased Mean Platelet Volume (MPV): median 13.1 fL (range 12-21.9 fL) 2
   • Increased Platelet Distribution Width (PDW): median 17.4 (range 14.9-19.6) 2
   • Potentially lower hemoglobin levels and higher Red Cell Distribution Width (RDW) 2

2. Peripheral Blood Smear:

   • Critical for diagnosis - shows giant platelets
   • Absence of Döhle body inclusions in leukocytes
   • Normal red blood cell morphology typically observed 2

3. Bleeding Time:

   • Usually normal despite thrombocytopenia (characteristic feature)

4. Platelet Function Tests:

   • Normal platelet aggregation studies (distinguishing it from functional platelet disorders)

Immunofluorescence Testing

Blood smear immunofluorescence labeling can be particularly helpful for differential diagnosis from other giant platelet disorders 3:

• Helps distinguish from MYH9-related disorders
• Can be performed on standard air-dried peripheral blood smears using less than 100 μL of blood
• Allows for diagnosis without requiring the patient to travel to specialized centers

Differential Diagnosis

Harris Syndrome must be differentiated from other inherited giant platelet disorders:

1. MYH9-related disorders (May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome):

   • Present with Döhle body-like inclusions in leukocytes
   • Often have associated features (hearing loss, nephritis, cataracts)

2. Bernard-Soulier Syndrome:

   • Presents with bleeding manifestations
   • Abnormal platelet glycoprotein Ib-IX-V complex

3. Gray Platelet Syndrome:

   • Characterized by gray-appearing platelets on blood smear
   • Alpha granule deficiency

4. Other macrothrombocytopenias:

   • GATA1, GFI1B, β1-tubulin, and filamin A-related thrombocytopenias

Management

The key management principle for Harris Syndrome is recognizing that despite thrombocytopenia, patients typically do not require specific treatment due to the absence of bleeding manifestations.

Treatment Considerations:

1. Observation and Monitoring:

   • Regular follow-up with CBC monitoring
   • No specific treatment needed for asymptomatic individuals

2. Patient Education:

   • Reassurance about benign nature of the condition
   • Education regarding the lack of bleeding risk despite low platelet counts

3. Perioperative Management:

   • Generally, no prophylactic platelet transfusions required before procedures
   • Individual risk assessment based on severity of thrombocytopenia

4. Avoid Unnecessary Interventions:

   • Prevent misdiagnosis as immune thrombocytopenia (ITP)
   • Avoid unnecessary treatments like corticosteroids or immunoglobulins

Special Considerations

1. Genetic Counseling:

   • Appears to have autosomal dominant inheritance pattern
   • Family screening may be appropriate

2. Regional Variations:

   • Higher prevalence in Indian subcontinent
   • Potential association with hemoglobinopathies in certain regions 2

3. Diagnostic Pitfalls:

   • May be misdiagnosed as immune thrombocytopenia
   • Automated platelet counters may underestimate platelet count due to large size

Conclusion

Harris Platelet Syndrome represents an important entity in the spectrum of inherited thrombocytopenias. The critical diagnostic feature is the combination of thrombocytopenia with giant platelets but without bleeding manifestations. Proper diagnosis through peripheral blood smear examination and platelet indices is essential to avoid unnecessary treatments and provide appropriate patient counseling.