Heparin-Induced Thrombocytopenia: Comparison Between the Standard Gel-Particle Assay (PaGIA) and the Functional Flow Cytometric Assay.

Heparin-induced thrombocytopenia and thrombosis (HIT) is an immune-mediated complication that may develop in patients sensitized to heparin. Approximately 5% of patients treated with full dose heparin develop clinical HIT, with about half develop thrombosis that may be associated with severe morbidity and death. However, antibodies may be detected in up to 30% of patients. Thus, current antibody-detection methods carry certain limitations, which pose a serious clinical dilemma in the diagnosis and treatment of HIT.

To compare the gel-particle immuno-assay (PaGIA) for the detection of antibodies against heparin-PF4 complex, with the functional flow cytometric assay (FCA) which determines the capacity of the patient's serum to activate platelets in the presence of heparin, similar in concept to the gold-standard, the radioactive Serotonin-release assay.

Sequential samples from patients clinically suspected for HIT were tested by both PaGIA and the FCA (Tomer 1997, 1999).

118 samples were tested. Positive: 9 (7.6%) patients tested positive by PaGIA, compared to 19 (16.1%) by the FCA. 7,out of the 9 (77.8%) PaGIA -positive samples were also positive by the FCA (relative sensitivity). Negative: 97 out of 109 gel-negative samples (89.0%) were also negative by the FCA (relative specificity). Thrombosis occurred in 3 of the 9 PaGIA-positive (33%) patients, and in 7 of the 19 FCA-positive (36.8%) patients. Of the 12 PaGIA -negative but FCA-positive patients, 4 (33%) had thrombosis. Death rate was also higher among FCA-positive (n=3) compared to PaGIA-positive (n=1) patients. Of the two PaGIA -positive but FCA-negative patients, one had APLA syndrome (APS) with chronic thrombocytopenia, and one had sepsis with cardiogenic shock and multiorgan failure.

ROC-Plot: Overall, the FCA showed significantly higher correlation with the clinical presentation of HIT (4Ts score), compared to the PaGIA (AUC 0.86 vs. 0.62, p<0.001)

The functional FCA demonstrates superior sensitivity and specificity compared to the antibody- detection PaGIA gel-particle assay. The feasible functional FCA (results in 1.5 hr) might be useful for initial diagnosis of HIT, and particularly for confirmation of HIT in patients with confounding presentation, including negative antibody-detection assay.

No relevant conflicts of interest to declare.