The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph.
OBJECTIVE
Protamine is routinely administered following cardiopulmonary bypass in order to neutralize the effects of heparin. An excess of protamine can contribute to coagulopathy, hence predisposing to bleeding with associated morbidity and mortality. Thromboelastography (TEG) is recognized as an invaluable bedside tool to detect coagulation parameters; however, the effects of protamine overdose on TEG parameters have not been fully established.


METHODS
Forty-six patients undergoing cardiac surgery using cardiopulmonary bypass were recruited in the study. Following heparinization, the patient's blood heparin level was measured using Hepcon HMS. Incremental doses of protamine [at a protamine-to-Hepcon-derived heparin ratio (PHR) of 1:1, 2:1 and 3:1] were added to patients' blood samples in vitro and four TEG coagulation parameters, including R (time to clot initiation), K (clot kinetics), alpha (clot kinetics) and maximum amplitude (ultimate clot strength), were monitored. Statistical analysis was performed using NCSS software.


RESULTS
Protamine caused dose-dependent worsening of coagulation parameters on TEG; K was significantly elevated, whereas alpha and maximum amplitude showed significant reduction (P < 0.001) compared with baseline at a PHR of 2:1 and 3:1, respectively. R was significantly prolonged compared with baseline (P < 0.001) at a PHR of 3:1.


CONCLUSIONS
Protamine adversely affects clot initiation time, clot kinetics and platelet function in a dose-dependent manner, which can predispose to bleeding.
Khan
Nouman U
NU
Department of Cardiothoracic Surgery, University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. n_u_khan@hotmail.com
Wayne
Charlotte K
CK
Barker
Julian
J
Strang
Timothy
T
D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D006493:Heparin / Q000008:administration & dosage*; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007700:Kinetics; D019106:Postoperative Hemorrhage / Q000097:blood / Q000139:chemically induced*; D011479:Protamines / Q000008:administration & dosage / Q000009:adverse effects*; D013916:Thrombelastography
D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin