Indeterminate serotonin release assays are associated with a high mortality rate

Shawn Jindal; Christopher Leyton; Fred Cohen; Morayma Reyes Gil; Henny Billett

doi:10.1002/rth2.12667

Indeterminate serotonin release assays are associated with a high mortality rate

Res Pract Thromb Haemost. 2022 Jun 14;6(4):e12667. doi: 10.1002/rth2.12667. eCollection 2022 May.

Authors

Shawn Jindal¹, Christopher Leyton¹, Fred Cohen¹, Morayma Reyes Gil², Henny Billett³

Affiliations

¹ Department of Medicine Montefiore Medical Center and the Albert Einstein College of Medicine Bronx New York USA.
² Department of Pathology Montefiore Medical Center and the Albert Einstein College of Medicine Bronx New York USA.
³ Division of Hematology Departments of Oncology and Medicine Montefiore Medical Center and the Albert Einstein College of Medicine Bronx New York USA.

Abstract

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 × 10⁶ 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.