The Effect of Excess Protamine on Thrombelastography in Vitro

Background: The aim of the current study was to assess the direct effect of protamine on conventional thrombelastography in vitro.

Methods: Protamine was added to blood samples collected from 25 adult cardiac surgical patients prior to the induction of anaesthesia and after separation from cardiopulmonary bypass. The final protamine concentrations were 0 (control), 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml (i.e. sufficient to reverse heparin 0, 5, 10 and 20 IU/ml respectively, assuming a 1:1 reversal ratio). In the pre-induction samples, protamine was associated with increases in r time and reductions in maximum amplitude (P<0.01). After bypass, the control samples demonstrated a heparin effect as expected, which was corrected by the addition of protamine 0.05 mg/ml. However, the higher concentrations of protamine were again associated with increases in r time and reductions in maximum amplitude (P<0.01).

Results & Conclusion: The results indicate that protamine has a direct anticoagulant effect on conventional thrombelastography in vitro. This effect occurs whether protamine is present alone, or whether protamine is present in excess after neutralization of heparin. Unless this effect is taken into account, excess protamine may confound the interpretation of conventional thrombelastography in cardiac surgical patients.