Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke

UMMS Affiliation

Department of Surgery

Publication Date


Document Type



Aged; Endarterectomy, Carotid; Female; Heparin Antagonists; Humans; Logistic Models; Male; Myocardial Infarction; New England; Odds Ratio; Postoperative Hemorrhage; Prospective Studies; Protamines; Registries; Reoperation; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome




OBJECTIVES: Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry.

METHODS: We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis.

RESULTS: Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death.

CONCLUSION: Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke, or death, in this large, contemporary registry. In light of significant complications referable to bleeding, liberal use of protamine during CEA appears warranted.

DOI of Published Version



J Vasc Surg. 2010 Mar;51(3):559-64, 564.e1. Epub 2010 Jan 4. Link to article on publisher's site

Journal/Book/Conference Title

Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter

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