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Hematology

Pseudo

Overview of Pseudothrombocytopenia

  • Definition: A falsely low platelet count reported by automated hematology analyzers due to in vitro platelet clumping or platelet satellitism. The actual platelet count in the patient is normal or only mildly reduced
  • Significance: Recognizing pseudothrombocytopenia is crucial to avoid misdiagnosis of true thrombocytopenia and to prevent unnecessary and potentially harmful investigations and treatments (e.g., bone marrow biopsy, platelet transfusions)
  • Key Feature: Platelet clumping or platelet satellitism is present on the peripheral blood smear, but the patient does not have clinical signs of bleeding (e.g., petechiae, purpura, easy bruising)

Mechanisms of Pseudothrombocytopenia

  • EDTA-Induced Platelet Clumping:

    • Most common cause of pseudothrombocytopenia
    • EDTA (ethylenediaminetetraacetic acid) is the anticoagulant used in most CBC collection tubes
    • In some individuals, EDTA triggers the exposure of cryptic platelet antigens (e.g., GPIIb/IIIa)
    • Autoantibodies (usually IgG or IgM) against these exposed platelet antigens cause platelets to clump together in vitro
    • The automated analyzer counts these clumps as single events, resulting in a falsely low platelet count

  • Platelet Satellitism:

    • Less common than platelet clumping
    • Platelets adhere to the surface of neutrophils or, less commonly, other blood cells (lymphocytes, RBCs)
    • The automated analyzer may misidentify these platelets as part of the white blood cell population, leading to an inaccurate platelet count

Laboratory Findings

  • Automated Platelet Count:

    • Falsely low platelet count (often significantly reduced)
    • The degree of thrombocytopenia can vary depending on the severity of the platelet clumping or satellitism

  • Peripheral Blood Smear:

    • Essential for diagnosing pseudothrombocytopenia
    • Platelet Clumps:
      • Aggregates of platelets are visible on the smear, ranging from small clumps to large aggregates
      • The clumps are often unevenly distributed on the smear
      • The presence of platelet clumping is essential for diagnosing EDTA-induced pseudothrombocytopenia
    • Platelet Satellitism:
      • Platelets adhere to the surface of neutrophils or other blood cells, forming a “ring” or “halo” around the cells
      • May be difficult to distinguish from true platelet adherence in some cases

Corrective Action Procedure

The following steps should be taken when pseudothrombocytopenia is suspected:

  1. Review the CBC Results and Peripheral Blood Smear:
    • Assess the platelet count and other CBC parameters
    • Examine the peripheral blood smear to confirm the presence of platelet clumping or platelet satellitism
  2. Repeat the CBC on a Sample Collected in a Different Anticoagulant:

    • This is the most important step

    • Collect a new blood sample in a tube containing sodium citrate (light blue top) or heparin (green top) as the anticoagulant

    • Citrate and heparin typically do not cause platelet clumping in individuals with EDTA-induced pseudothrombocytopenia

    • Important Note: Sodium citrate dilutes the blood sample, so the platelet count obtained from the citrate tube must be multiplied by a correction factor (usually 1.1) to account for the dilution:

      Corrected Platelet Count = Platelet Count (Citrate Tube) x 1.1

  3. Perform a Manual Platelet Count:
    • If platelet clumping persists despite using an alternative anticoagulant, a manual platelet count may be necessary
    • Prepare a well-made peripheral blood smear and count platelets manually, avoiding areas with platelet clumping
    • Use a microscope with a calibrated eyepiece graticule to count platelets in a defined area or number of fields
  4. Warm the Sample:
    • Warming the sample to 37°C may help disperse platelet clumps in some cases
    • Incubate the sample at 37°C for 15-30 minutes before re-analyzing
  5. Dilution:
    • Diluting the sample with saline or another appropriate diluent may help disperse platelet clumps
    • Ensure that the dilution factor is accounted for when calculating the final platelet count
  6. Rule Out Other Causes of Thrombocytopenia:
    • If the platelet count remains low despite corrective actions, consider other causes of true thrombocytopenia, such as:
      • Increased platelet destruction (e.g., ITP, TTP, HIT)
      • Decreased platelet production (e.g., bone marrow failure)
  7. Documentation and Reporting:
    • Clearly document all corrective actions taken in the patient’s laboratory record, including:
      • The initial platelet count and the presence of platelet clumping on the smear
      • The type of anticoagulant used for the repeat sample
      • The corrected platelet count (if applicable)
      • A comment indicating that pseudothrombocytopenia was present and that the results were corrected accordingly
    • Report the corrected platelet count to the physician, noting that pseudothrombocytopenia was identified
  8. Communication with the Physician:
    • Notify the physician about the presence of pseudothrombocytopenia and the corrective actions taken
    • Explain the potential for falsely low platelet counts and the importance of relying on the corrected results
    • Discuss the need for further investigation if the patient has clinical signs of bleeding or if the corrected platelet count is significantly low

Key Considerations

  • Prompt Action: It’s essential to take prompt action when pseudothrombocytopenia is suspected to avoid unnecessary investigations and treatments
  • Visual Confirmation: Always confirm the presence of platelet clumping or satellitism on the peripheral blood smear before initiating corrective actions
  • Accuracy: Ensure accurate measurement and replacement of plasma volume when performing saline replacement procedures
  • Documentation: Thorough documentation of the procedure and results is essential for accurate reporting and patient management
  • Communication: Clear communication with the physician is critical for ensuring appropriate clinical decision-making

Key Terms

  • Pseudothrombocytopenia: Falsely low platelet count due to in vitro platelet clumping or satellitism
  • EDTA: Ethylenediaminetetraacetic acid, the anticoagulant used in most CBC tubes
  • Platelet Clumping: Aggregation of platelets in vitro
  • Platelet Satellitism: Adherence of platelets to other blood cells
  • Corrected Platelet Count: The platelet count obtained after correcting for the effects of dilution or other factors