Effects of Protamine Reversal on Coagulation Parameters After High-Dose Heparin Administration in Percutaneous Hepatic Chemosaturation Intervention.

Abstract

Background: Intravenous protamine administration for heparin reversal after percutaneous hepatic chemosaturation intervention is generally recommended, but its effectiveness on coagulation parameters remains unclear.

Methods: In a single-center retrospective observational study, the effects of different postinterventional protamine doses on the activated partial thromboplastin time (aPTT), international normalized ratio (INR), prothrombin time (PT), fibrinogen, platelet count (PLT), and hemoglobin (Hb) were analyzed in consecutive patients who underwent high-dose heparin administration (>300 U/kg body weight) and extracorporeal circulation for chemosaturation treatment. Due to the multiple treatments of individual patients, linear mixed-effects models were applied.

Results: Thirty-one patients underwent 90 chemosaturation interventions, 68 (75.6%) of which involved heparin reversal with protamine. All investigated variables showed significant postinterventional alterations, while protamine use was associated with significantly lower aPTT, lower INR, higher PT, and higher fibrinogen levels, whereas PLT and Hb levels were comparable to those in procedures without protamine use. After adjustment for aPTT, significant independent effects of protamine remained for the INR and PT. Dose-dependent effects of protamine were observed for reductions in aPTT and an increase in fibrinogen levels, which were confirmed after adjustment for the heparin dose. A 10% higher protamine dose resulted in a 3% decrease in aPTT and a 4% increase in fibrinogen. An increase of 0.1 in the protamine-to-heparin ratio was associated with an increase of 9% in fibrinogen.

Conclusions: The present results suggest that protamine contributes to the normalization of the aPTT, INR, PT, and fibrinogen levels. Further prospective studies should be conducted to determine optimal dosing ratios.