A buffer-positive serotonin release assay pattern is associated with increased mortality in HIT: a retrospective cohort study

HIT is an anti-platelet factor 4 (PF4) disorder characterized by thrombocytopenia and increased thrombosis risk. The serotonin release assay (SRA) is the gold standard test for diagnosing HIT. The clinical significance of a buffer-positive SRA pattern remains uncertain.

This study compared characteristics and outcomes between patients with HIT with buffer-negative and buffer-positive SRA patterns.

We conducted a retrospective cohort study at the Hospital of the University of Pennsylvania and affiliated hospitals. Consecutive patients with confirmed HIT, defined as a positive PF4/heparin enzyme-linked immunoassay and platelet-rich plasma-based SRA without a high-heparin inhibition step, were classified by an SRA pattern (buffer-negative vs buffer-positive) and followed for 30 days. The primary outcome was cumulative incidence of thrombosis; secondary outcomes included mortality, major bleeding, and platelet recovery.

Of 207 HIT-positive patients, 190 (91.8%) had a buffer-negative and 17 (8.2%) had a buffer-positive SRA pattern. Median anti-PF4/heparin enzyme-linked immunoassay optical density was significantly lower in the buffer-positive group (0.8 vs 2.3; P < .001). Thrombosis incidence was similar between groups (64.7% vs 50.2%; P = .28). The buffer-positive pattern was independently associated with longer time to platelet recovery (9.0 vs 5.0 days; P = .03) and higher 30-day cumulative incidence of death (47.4% vs 17.1%; adjusted hazard ratio, 2.74; P = .03).

Among patients with HIT, a buffer-positive SRA pattern was associated with more prolonged thrombocytopenia and increased mortality. Given that our assay used platelet-rich plasma, these findings are hypothesis-generating and require confirmation with the classical washed-platelet SRA.