Are platelet clumps normal?

Platelet Clumps in Laboratory Testing: Clinical Significance and Management

Platelet clumps are not normal and represent a laboratory phenomenon called pseudothrombocytopenia that can lead to falsely low platelet counts and potentially unnecessary medical interventions. 1

What Are Platelet Clumps?

Platelet clumps are aggregates of platelets that form in vitro (in the collection tube) rather than in the patient's circulation. This phenomenon:

• Creates falsely decreased platelet counts (pseudothrombocytopenia)
• May cause spurious leukocytosis when automated analyzers misidentify clumps as white blood cells 2
• Occurs most commonly due to the anticoagulant EDTA used in blood collection tubes 1

Identification of Platelet Clumping

When platelet clumping is suspected:

1. Examine the peripheral blood smear - This is essential to verify automated counts and identify platelet clumps 3
2. Collect blood in alternative anticoagulants - Repeat testing using tubes containing:
   • Sodium citrate
   • Heparin 4
3. Assess flagging features on automated analyzers:
   • Modern analyzers like Sysmex XN-10 have "platelet clumps" and "platelet abnormal" flags
   • These flags have varying sensitivity (62.6% for platelet clumps flag) and specificity (94.7%) 5

Clinical Implications

When to Suspect Pseudothrombocytopenia

• Discrepancy between platelet count and patient's clinical condition (no bleeding)
• Isolated thrombocytopenia with no other abnormalities
• Previous normal platelet counts with sudden unexplained drop
• Inappropriate leukocytosis that cannot be verified on blood smear examination 2

Distinguishing from True Thrombocytopenia

True thrombocytopenia (platelet count <150 × 10³/μL) can result from:

1. Decreased production - bone marrow disorders
2. Increased destruction - immune thrombocytopenia (ITP)
3. Splenic sequestration - hypersplenism
4. Dilution - massive transfusion 4

Management Approach

When platelet clumps are identified:

1. Report the finding to the ordering clinician
2. Add a comment to the laboratory report indicating pseudothrombocytopenia
3. Redraw the sample using alternative anticoagulants:
   • Sodium citrate
   • Heparin
   • Immediate processing of the sample 1, 5
4. Avoid unnecessary interventions such as:
   • Platelet transfusions
   • Immunosuppressive therapy
   • Bone marrow examination
   • Activity restrictions 4

Special Considerations

Distinguishing from Pathological Conditions

Some inherited platelet function disorders may present with abnormal platelet aggregation:

• Wiskott-Aldrich Syndrome (WAS) - X-linked disorder with small platelets, thrombocytopenia, eczema, and recurrent infections 3
• 22q11.2 Deletion Syndrome - Associated with mild to moderate thrombocytopenia and increased platelet volume 3
• Bernard-Soulier Syndrome - Severe bleeding disorder with giant platelets 3

Laboratory Testing Pitfalls

• Automated cell counters may misclassify platelet clumps as white blood cells, causing spurious leukocytosis 2
• Platelet clumps can affect not only platelet counts but also leukocyte counts and erythrocyte indices 5
• The sensitivity of automated analyzers to detect platelet clumps varies based on the platelet count (more sensitive with low counts) 5

Conclusion

Platelet clumping is a laboratory phenomenon that should be recognized to avoid misdiagnosis and unnecessary interventions. When identified, alternative collection methods should be used to obtain accurate platelet counts. The peripheral blood smear remains an essential tool in distinguishing pseudothrombocytopenia from true thrombocytopenia.