Pseudothrombocytopenia and other conditions associated with spuriously low platelet counts

Accurate measurements of the platelet count are necessary to diagnose thrombocytosis or thrombocytopenia correctly, gauge the severity of clinical risk and identify the most appropriate therapeutic intervention. Despite increased diagnostic accuracy with electronic counters, counting is still unsatisfactory in rare situations. Conditions causing spurious thrombocytopenia include the following. (i) Pre-analytical errors, such as difficult venipuncture, over-/under-filling of blood collection tubes, insufficient mixing of blood with the anticoagulant (EDTA), which may cause fibrin formation. (ii) EDTA-induced, temperature- and time-dependent, antibody-mediated in vitro platelet agglutination, with consequent reduction in the number of single platelets in the sample; this condition, referred to as pseudothrombocytopenia, is benign and does not need follow-up or medical interventions; the use of alternative in vitro anticoagulants does not prevent formation of agglutinates in all samples; accurate platelet counts could be obtained by testing EDTA-samples immediately after blood collection. (iii) EDTA-induced in vitro platelet adherence to leukocytes (platelet satellitism), caused by bridging IgG antibodies binding to GPIIb-IIIa on platelets and the Fc receptor-III on leukocytes; occasionally, leukocytes may phagocytose platelets and/or form platelet/leukocyte clumps. (iv) The presence of large/giant platelets (commonly from patients with congenital or acquired thrombocytopenia) that are not recognized as such by electronic counters, which distinguish platelets from other cells based on their smaller size. (v) Type 2B von Willebrand disease: blood from patients with this disorder may display large/giant platelets and platelet agglutinates. All the above conditions are easily identifiable by microscopic examination of anticoagulated peripheral blood smears, which is an indispensable diagnostic procedure in hematology.