Cardiovascular
Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem®): an in vitro study

https://doi.org/10.1093/bja/aei197Get rights and content
Under an Elsevier user license
open archive

Background

Precise coagulation monitoring might help prevent heparin–protamine mismatch and thus decrease postoperative blood loss. We therefore measured coagulation time (CT) by modified thrombelastography (Rotem®) as a possible differential monitor of the effects of heparin and protamine.

Methods

Undiluted and diluted blood samples from 26 healthy volunteers were spiked with increasing concentrations of heparin (0.1, 0.2, 0.4, 0.8 and 1 U ml−1). In addition, undiluted blood was spiked with protamine hydrochloride (0.1, 0.2, 0.4, 0.8 and 1.6 U ml−1), and we tested the effect of protamine on the reversal of heparin 0.4 U ml−1. Heparin-containing samples were analysed using the heparin-sensitive INTEM test and the heparinase-containing HEPTEM test; protamine series were also analysed with the EXTEM test (tissue factor activation).

Results

CT by the INTEM test [CT-INTEM; median (min/max)] increased significantly and dose-dependently with increasing concentrations of heparin [control, 175 s (146/226); heparin, 1.0 U ml−1 1320 s (559/2100); P<0.001] and protamine [control, 172 s (150/255); protamine, 1.6 U ml−1 527 s (300/1345); P<0.0001]. Up to heparin concentrations of 0.4 U ml−1, results were similar in undiluted and diluted blood samples. As expected, CT-HEPTEM remained within the normal range for all tested heparin concentrations (median 180–183 s), but increased similarly to CT-INTEM for increasing protamine concentrations.

Conclusion

CT measurement using the Rotem® technique appears to be a valuable tool for heparin–protamine management. For detection of heparin alone, protamine alone and the two combined, the ratio of CT-INTEM:CT-HEPTEM can be used to distinguish the effects of heparin excess (CT-INTEM:CT-HEPTEM>1) from those of protamine excess (CT-INTEM:CT-HEPTEM=1).

Keywords

blood, anticoagulants, heparin
measurement techniques, thrombelastography, Rotem®
protamine

Cited by (0)