Figure 2.
Algorithm for rapid HIT diagnosis developed from retrospective and prospective derivation cohorts. The first step is to assess the pretest probability for HIT with the 4T score. In case of a 4T score ≥2 and/or unexplained heparin resistance, the automated CLIA HIT-IgG is performed as the first-line test, which (using conservative 100% NPV and PPV cutoff values) is expected to solve ∼80% of cases with an analytical TAT of 30 minutes. For the remaining ∼20% of cases with results situated in the CLIA intermediate gray zone, the PaGIA testing is performed as the second-line test. This additional assay takes 30 minutes and is expected to solve at least 50% of cases that were situated in the CLIA intermediate gray zone. Of note, the 95% CI of the posttest probability depends on the pretest probability for HIT and the LR of the quantitative IA result. Finally, for the ≤5% of cases that remain unresolved despite a combination of 4T score, CLIA, and PaGIA (HIT undetermined), individualized clinical judgment will define initial management decisions, while awaiting the results of the functional HIPA assay as the diagnostic gold standard.