| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee
Address correspondence and reprint requests to Brian S. Donahue, MD, PhD, Department of Anesthesiology, 504 Oxford House, Vanderbilt University, Nashville, TN 37232. Address e-mail to brian.donahue{at}vanderbilt.edu
Activated protein C (aPC) resistance is a recognized hypercoagulable phenotype that is associated with increased risk for thrombosis in multiple clinical settings. Factor V Leiden (FVL) represents a specific inherited cause of aPC resistance, but the perioperative thrombotic risk of FVL is unclear. In this investigation, we sought to quantify whether cardiopulmonary bypass produces alterations in aPC resistance in FVL carriers and noncarrier controls, testing the hypothesis that FVL is associated with a relatively hypercoagulable postoperative state. Two-hundred-five adult cardiac surgery patients were prospectively enrolled into a genetic registry whose purpose was to study the impact of genetic variables on clinical outcomes. For this study, 8 subjects heterozygous for FVL were identified (group L), as well as 2 control groups: group MC, matched controls, 18 matched subjects without FVL; and group UC, unmatched controls, 11 consecutive subjects without FVL. Plasma was sampled at the beginning of surgery, 10 min after protamine administration, and on postoperative day 1, and assayed for resistance to aPC (normal aPC ratio is >2.0). Both MC and UC groups exhibited normal aPC ratio at baseline (2.40 and 2.36, respectively), which increased significantly (to 2.76 and 2.75, P = 0.007 and 0.021, respectively) on postoperative day 1, indicating increased postoperative sensitivity to aPC. Conversely, group L subjects exhibited aPC resistance at baseline (aPC ratio 1.80), and did not change significantly postoperatively (P = 0.867). Patients without FVL therefore show laboratory evidence consistent with relative protection from postoperative thrombosis, whereas FVL carriers do not. These findings provide mechanistic support for previous speculations of increased postoperative thrombotic risk associated with FVL.
IMPLICATIONS: Patients without factor V Leiden (FVL) have increased sensitivity to the activated protein C after cardiac surgery, whereas FVL carriers do not. These data provide mechanistic support for previous speculations that FVL subjects are at increased postoperative thrombotic risk relative to noncarriers.
|
