title: The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK. n_u_khan@hotmail.com
authors.forename: Nouman U
authors.initials: NU
authors.lastname: Khan
authors.forename: Charlotte K
authors.initials: CK
authors.lastname: Wayne
authors.forename: Julian
authors.initials: J
authors.lastname: Barker
authors.forename: Timothy
authors.initials: T
authors.lastname: Strang
mesh_terms: 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
chemical_list: D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin