Low-Range Heparin and Protamine Detection: A Single-Center Prospective Diagnostic Study.

Abstract

Objectives: The detection of low-range heparin activity is important to correctly assess heparin reversal and rebound, especially after cardiopulmonary bypass. Current parameters are either not available at point-of-care (anti-Xa activity [aXa] and activated partial thromboplastin time [aPTT]), insensitive (kaolin-activated clotting time [kACT]), or expensive (ROTEM viscoelastic test). We aimed to assess the performance of a recently proposed parameter from the Sonoclot viscoelastic test: the slope-45. We aimed to assess the effects of a range of low-dose heparin and protamine and their interaction on multiple proposed parameters.

Design: Prospective in vitro volunteer study.

Setting: Single-center university teaching hospital.

Participants: Healthy volunteers.

Interventions: Blood samples from healthy volunteers (n = 10) were treated ex vivo with incremental low doses of heparin, protamine, or their combination. In the combination cycle, theoretical reversal ratios were 25%, 62.5%, 100%, and 200% of the highest heparin dose, based on a unit-for-unit reversal. We compared the effects on aXa, aPTT, iSTAT kACT, ROTEM clotting time ratio, and the novel Sonoclot slope-45 parameter, and we performed receiver operating curve analysis.

Measurements and main results: In heparin-spiked blood, all parameters except iSTAT kACT were able to reliably detect low heparin activity. Protamine, both in isolation and combined with heparin, showed no impact on aXa, aPTT, iSTAT kACT, ROTEM clotting time ratio, and the novel Sonoclot slope-45 parameter.

Conclusions: We were able to confirm that the Sonoclot slope-45 has a high sensitivity for low-dose heparin, which is retained in the setting of interacting protamine. It was insensitive to protamine in itself.