The most common etiology of pseudothrombocytopenia is platelet clumping induced by EDTA, which is the anticoagulant present in the purple tube in which blood is collected for a CBC. This clumping is probably attributable to a naturally occurring platelet autoantibody directed against a normally concealed epitope localized on the platelet membrane glycoprotein IIb/IIIa. When EDTA exposes this membrane, it leads to the dissociation of glycoprotein IIb/IIIa. Immunoglobulin (Ig) M, IgG, and IgA have all been implicated in the pathogenesis of EDTA-inducing platelet clumping. This is not an aggregation reaction because none of the various phases linked to the activation and release of mediators of aggregating activity has been documented in pseudothrombocytopenia.

EDTA-induced pseudothrombocytopenia has been reported in association with infectious mononucleosis, cold agglutinin disease (IgM), multiple myeloma, liver cirrhosis, preterm neonates, abciximab therapy, and other conditions.1,7-9

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Platelet satellitism refers to the adherence of platelets to polymorphonuclear leukocyte surfaces due to specific IgG antibodies directed to the glycoprotein IIb-IIIa complex in platelets. This reaction leads to a reduction in the number of free platelets and a spurious thrombocytopenia. This phenomenon has been observed only in the presence of EDTA and does not occur when other anticoagulants are used for specimen collection or when a platelet count is done in a nonanticoagulated blood sample. Because platelet satellitism has not been observed in association with eosinophils, basophils, lymphocytes, or monocytes, only the neutrophils are the target cells. This condition has been reported in patients with active Behcet’s disease and thrombocythemia.10 In EDTA-induced platelet clumping and satellitism, the pathogenic mechanism depends on the presence of specific antibodies and is independent of the possible existence of rare antigenic subgroups.10,11

The giant platelet syndromes are rare conditions. These have been described as part of the Bernard-Soulier syndrome, von Willebrand disease type 2B, the May-Hegglin anomaly, the gray platelet syndrome, and others.6

A diagnosis of pseudothrombocytopenia can be established by (1) reviewing the peripheral blood smear, looking for platelet clumps, platelet satellitism, or giant platelets; (2) obtaining a platelet count in a tube containing heparin or citrate; or (3) performing a manual platelet count.

For the specific diagnosis of EDTA-induced thrombocytopenia, follow these steps:

  • Collect the blood specimen in an EDTA-containing tube.
  • Perform a platelet count at time 0.
  • Repeat the platelet count at times 1h, 2h, and so forth.
  • Observe the decrement in the platelet count as the blood sample has been exposed over time to EDTA.2-5,9,12,13

3. Conclusion

Ms. J was found to have falsely low platelet count due to platelet clumping, most likely EDTA-induced thrombocytopenia. None of the reported diseases associated with pseudothrombocytopenia were found during her evaluation; therefore, the most likely etiology was idiopathic.

Pseudothrombocytopenia, especially EDTA-induced, is a rare finding. From the clinical point of view, pseudothrombocytopenia does not carry any significance since this is a laboratory phenomenon, and there is no need for further workup or therapy. Nevertheless, the condition represents a diagnostic challenge for health-care providers. In all cases of a decreased platelet count, pseudothrombocytopenia should be excluded early to avoid diagnostic tests and treatment interventions that result in unnecessary utilization of resources as well as potential deleterious side effects for patients.

All three authors are affiliated with Woodhull Medical Center in Brooklyn, N.Y. Dr. Hidalgo is director of hematology-oncology, Dr. Díaz is a medical volunteer in the New York University Cancer Center, and Dr. Karki is a resident in the department of medicine.


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All electronic documents accessed August 15, 2010.