Indeterminate serotonin release assays are associated with a high mortality rate

BACKGROUND: The serotonin release assay (SRA) is considered the gold standard for diagnosis of heparin‐induced thrombocytopenia (HIT). Although the SRA holds high sensitivity and specificity when results are definitive, up to 10% of samples from patients with suspected HIT yield “indeterminate” results. OBJECTIVES: We aimed to study the clinical course of patients with indeterminate results. METHODS: We conducted a cohort analysis of 2056 patients that underwent SRA testing. RESULTS: Of 2056 total patients, 152 (7.4%) had indeterminate assays. The prevalence of thrombocytopenia <50,000 × 10(6) was higher in patients with an indeterminate or positive SRA, compared with a negative SRA (39.5% and 40.0% vs. 27.5%, p < 4.0 × 10(–4)). Patients with an indeterminate SRA were more likely to have been treated in the intensive care unit than patients with a positive SRA (93.3% vs. 73.7%, p = 0.03). The mean thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes for thrombocytopenia score in patients with indeterminate SRA was 2.9, corresponding to a HIT probability of <5%. Of 152 patients, 128 (78.9%) had heparin‐PF4 optical densities (ODs) below 0.60 OD, whereas four patients (2.6%) had ODs above 2.00 OD. Inpatient mortality was significant in patients with indeterminate SRAs compared with positive or negative SRA (49.3% vs. 21.1% and 27.2%, p < 2.4 × 10(–10)). CONCLUSIONS: Our data suggest that an indeterminate SRA may signal an in vivo platelet activation process that is not related to heparin but is associated with increased mortality.