Work

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

Year: 2026

Type: article

Abstract: Background Heparin-induced thrombocytopenia (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 HIT patients 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 (ELISA) and platelet-rich plasma-based SRA without a high-heparin inhibition step, were classified by 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 ELISA optical density was significantly lower in the buffer-positive group (0.8 vs. 2.3; P < 0.001). Thrombosis incidence was similar between groups (64.7% vs. 50.2%; P=0.275). The buffer-positive pattern was independently associated with longer time to platelet recovery (9.0 vs. 5.0 days; P=0.026) and higher 30-day cumulative incidence of death (47.4% vs. 17.1%; adjusted HR 2.74; P=0.033). Conclusions 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.

Source: Research and Practice in Thrombosis and Haemostasis

DOI: 10.1016/j.rpth.2026.106995

Authors: Tarinee Rungjirajittranon, Theodore E. Warkentin, Adam Cuker

Institutions: Siriraj Hospital, Mahidol University, University of Pennsylvania, McMaster University

Language: English

Topic: Heparin-Induced Thrombocytopenia and Thrombosis

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,250