A buffer-positive serotonin release assay pattern is associated with increased mortality in HIT: a retrospective cohort study
- 1Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- 2Department of Pathology and Molecular Medicine, Department of Medicine, and McMaster Centre for Transfusion Research, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- 3Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Abstract
Background
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.Objectives
This study compared characteristics and outcomes between patients with HIT with buffer-negative and buffer-positive SRA patterns.Methods
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.Results
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).Conclusion
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.
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BibTeX
@article{rungjirajittranon2026bufferpositive,
title = {{A buffer-positive serotonin release assay pattern is associated with increased mortality in HIT: a retrospective cohort study}},
author = {Tarinee Rungjirajittranon and Theodore E. Warkentin and Adam Cuker},
journal = {Research and practice in thrombosis and haemostasis},
year = {2026},
month = sep,
doi = {10.1016/j.rpth.2026.106995},
url = {https://europepmc.org/article/PMC/PMC13717026},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A buffer-positive serotonin release assay pattern is associated with increased mortality in HIT: a retrospective cohort study
AU - Tarinee Rungjirajittranon
AU - Theodore E. Warkentin
AU - Adam Cuker
PY - 2026
DA - 2026/09/28
JO - Research and practice in thrombosis and haemostasis
DO - 10.1016/j.rpth.2026.106995
UR - https://europepmc.org/article/PMC/PMC13717026
AB - Background 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.Objectives This study compared characteristics and outcomes between patients with HIT with buffer-negative and buffer-positive SRA patterns.Methods 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.Results 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).Conclusion 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.
SN - 2475-0379
ER -