Cardiovascular

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

TL;DR

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

Key Findings

About 8% of confirmed HIT patients had a buffer-positive SRA pattern.

  • Of 207 HIT-positive patients, 190 (91.8%) had a buffer-negative and 17 (8.2%) had a buffer-positive SRA pattern.
  • Retrospective cohort at the Hospital of the University of Pennsylvania and affiliated hospitals.
  • HIT was confirmed by a positive PF4/heparin ELISA and a platelet-rich plasma-based SRA without a high-heparin inhibition step; patients were followed for 30 days.

The buffer-positive group had significantly lower anti-PF4/heparin ELISA optical density.

  • Median optical density was 0.8 in the buffer-positive group vs 2.3 in the buffer-negative group (P < .001).

Thrombosis incidence did not differ significantly between buffer-positive and buffer-negative patients.

  • Thrombosis incidence was 64.7% vs 50.2% (P = .28).
  • Cumulative incidence of thrombosis was the primary outcome.

The buffer-positive pattern was independently associated with longer time to platelet recovery.

  • Median time to platelet recovery was 9.0 vs 5.0 days (P = .03).
  • The association was independent in adjusted analysis.

The buffer-positive pattern was associated with higher 30-day mortality.

  • 30-day cumulative incidence of death was 47.4% vs 17.1%.
  • Adjusted hazard ratio was 2.74 (P = .03).

The authors characterize the findings as hypothesis-generating because of the assay type used.

  • The assay used platelet-rich plasma rather than the classical washed-platelet SRA.
  • Confirmation with the washed-platelet SRA is required.

What This Means

Heparin-induced thrombocytopenia (HIT) is a dangerous reaction to the blood thinner heparin, in which platelet counts fall and clotting risk rises. The serotonin release assay (SRA) is the gold-standard lab test for it. Some patients' samples show platelet activation even without heparin (a 'buffer-positive' pattern), and it has been unclear what this means clinically. Researchers reviewed 207 patients with confirmed HIT at the University of Pennsylvania hospitals. About 8% (17 patients) had a buffer-positive pattern. These patients had lower levels of the HIT antibody on a screening test, took longer for platelet counts to recover (9 vs 5 days), and were more likely to die within 30 days (47% vs 17%). After adjustment for other factors, the risk of death was about 2.7 times higher. Rates of blood clots were not significantly different between groups. This research suggests a buffer-positive pattern might mark a sicker group of patients or a different disease process. However, the group was small, the study was retrospective, and the lab used a platelet-rich plasma version of the test rather than the classical washed-platelet method. The authors therefore describe the results as hypothesis-generating, needing confirmation in further studies.

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Citation

Rungjirajittranon T, Warkentin T, Cuker A. (2026). A buffer-positive serotonin release assay pattern is associated with increased mortality in HIT: a retrospective cohort study.. Research and practice in thrombosis and haemostasis. https://doi.org/10.1016/j.rpth.2026.106995