Performance evaluation of a reflexive algorithm for suspected heparin-induced thrombocytopenia.

BACKGROUND

The diagnostic workup of heparin-induced thrombocytopenia (HIT) involves a heparin-platelet factor 4 complex-dependent screening test, such as an enzyme-linked immunosorbent assay (ELISA) or a rapid latex immunoturbidimetric assay (LIA), followed by a heparin-dependent platelet activation assay. Because of the high false-positive rates observed with LIA alone in our hospital, our laboratory adopted a reflex algorithm in which LIA-positive results are confirmed by an immunoglobulin G-specific ELISA before evaluation with serotonin release assay (SRA).

OBJECTIVES

To evaluate the diagnostic performance and operational impact of an LIA-first reflex ELISA algorithm for suspected HIT compared with ELISA or LIA alone.

METHODS

We retrospectively compared ELISA alone, LIA alone, and LIA with reflex ELISA confirmation across 3 diagnostic eras, with performance assessed against SRA-confirmed HIT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy were calculated for each era, and associations between the magnitudes of screening-assay reactivity and SRA positivity were assessed.

RESULTS

PPV improved from 31.3% with ELISA alone and 25.3% with LIA alone to 61.2% with reflex testing, while accuracy improved from 39.8% and 33.3% to 63.5%, respectively. Reflex ELISA confirmation reduced the number of patients classified as screening positive from 127 of 804 to 49 of 804, corresponding to a 61.4% reduction in potential SRA send-outs and a decrease from 15.8 to 6.1 SRA send-outs per 100 patients evaluated. Higher combined LIA and ELISA reactivities were associated with higher probability of SRA positivity.

CONCLUSION

Reflex ELISA confirmation improved the diagnostic efficiency of HIT evaluation by increasing PPV and accuracy while reducing SRA send-outs. Combined screening-assay strength may help stratify the likelihood of HIT and guide the need for confirmatory testing, potentially improving time to HIT diagnosis and management in certain scenarios.