Pseudothrombocytopenia needs to be differentiated from True thrombocytopenia to avoid unnecessary clinical decisions and platelet transfusions.

Definition:

Pseudothrombocytopenia or spurious thrombocytopenia is defined as falsely low (<150 x 109 /L) platelet count due to in-vitro or in-vivo factors causing platelet clumping.

Causes of Pseudothrombocytopenia

  • Method of collection –capillary, venous or line draws are prone to clotting and formation of platelet clumps.• EDTA dependent thrombocytopenia.
  • Incompletely mixed or inadequately anticoagulated samples.•Platelet satellitism (platelets may rosette around WBCs).
  • Giant platelets, Cold agglutinins, Paraproteins, Hyperlipidemia.• Contact with foreign surfaces such as dialysis membrane.
  • Certain Viral infections.
  • Drug induced platelet clumping (Eg: Abciximab).
  • Clumping can also be due to a combination of more than one of the above factors.

Pathophysiology:

EDTA induces in vitro agglutination of platelets in the blood collection tube caused by IgM/IgG autoantibodies directed against epitopes on platelet surface glycoprotein (GP) IIb/IIIa. EDTA induces a conformational change in GPIIb/IIIa, exposing these epitopes and resulting in platelet agglutination. Administration of GPIIb/IIIa inhibitors (eg, eptifibatide, tirofiban, abciximab) has also been implicated in this mechanism. Incompletely mixed or inadequately anticoagulated samples may form a clot that traps platelets in the collection tube and prevents them from being counted. Cold agglutinins, Paraproteins, Hyperlipidemia also induces platelet clumping. Giant platelets may be counted by automated counters as red blood cells rather than platelets.

Recommendations:

From a practical laboratory point of view, investigation of platelet clumping may include the following steps until a non-clumping smear is obtained.Step-1: Verify method of blood draw (e.g., finger stick versus venipuncture versus line draw) and exclude collection method related clotting.

Step-1: Verify method of blood draw (e.g., finger stick versus venipuncture versus line draw) and exclude collection method related clotting.

Step-2: Test a blood sample collected in sodium citrate. However, up to 17% of patients with EDTA-Pseudothrombo-cytopenia also show this phenomenon with citrate. If clumping persists, continue to Step 3 Step-3: Test a sample collected in heparin.

Modern hematology analyzers “flag” platelet clumps and this should prompt manual verification by examination of a stained peripheral blood smear.

Conclusion:

Diagnosis of thrombocytopenia without confirmation on the peripheral smear may expose patients to unnecessary diagnostic procedures and mismanagement. A microscopic examination can identify platelet clumping, repeat CBP tests using a different anticoagulant and clinical correlation can confirm the diagnosis.

Contributed by: DR.A.BHEEMAVATHI MD (Pathology)