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


CONCLUSIONS
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).
Mittermayr
M
M
Clinic for Anaesthesia and Intensive Care Medicine, Innsbruck Medical University, Innsbruck, Austria. markus.mittermayr@uibk.ac.at
Margreiter
J
J
Velik-Salchner
C
C
Klingler
A
A
Streif
W
W
Fries
D
D
Innerhofer
P
P
D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000097:blood / Q000494:pharmacology*; D006494:Heparin Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D011479:Protamines / Q000494:pharmacology*; D013916:Thrombelastography / Q000379:methods; D014914:Whole Blood Coagulation Time / Q000379:methods
D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin