Role of Gender in Venous Bypass Graft Thrombosis Due to Hypercoagulability
Robert S. Poston, M.D.
School of Medicine, University of Maryland, Baltimore

Compared with men, women have been found to suffer a consistently higher rate of complications after coronary artery bypass (CAB) sugery such as death, stroke, and prolonged hospitalization. The recent evolution of off-pump coronary bypass (OPCAB) has been reported to reduce postoperative adverse outcomes, particularly in higher risk groups such as women. However, there are reasons to be concerned that OPCAB may compromise the long term benefits of the operation in women by increasing the chance that veins used to bypass the blocked coronary arteries develop early failure. First, the compromised precision required to suture the vein to the coronary artery in the beating heart may increase the risk of technical defects of OPCAB, particularly with smaller female coronary arteries. Fortunately, routinely quantifying blood flow in the vein following the completion of the coronary bypass is a reliable method of detecting (and therefore minimizing the impact of) potential technical defects. Second, women as a group show a tendency towards aggressive clot formation, which in many is not prevented by aspirin. The use of the heart-lung bypass machine necessary for standard CAB is associated with a transient disruption in the ability to effectively form clot. Paradoxically, the absence of heart-lung bypass in OPCAB may further exacerbate clot formation in women, leading to early bypass failure due to inappropriate clot inside the vein used for the bypass. The role of blood clotting on graft failure has not been established in large part due to the difficulty in documenting that clotting is excessive using a laboratory test. We propose to investigate blood clotting in women following OPCAB by analyzing the speed (reaction, "r" time), strength (maximum amplitude, "MA") and stability (amplitude at 30 minutes, "Lys₃₀") of clot viscoelasticity using a machine called thrombelastography (TEG). By integrating the myriad of interdependent biochemical cascades necessary to understand excessive clot formation, the TEG may provide previously unexplored insights into the relationship of gender and graft patency following OPCAB.

These studies were designed to address two questions:

1. Does thrombelastography provide an accurate, reproducible and clinically relevant method of identifying women who are at increased risk of developing inappropriate clot inside the veins used to perform the coronary bypass procedure?
2. How does reduced blood flow through veins used to bypass coronary blockages in women influence the role that excessive clotting plays in early bypass failure?

The less optimal outcomes seen in women after CAB may be related in part to an increase in adverse events related to excessive clot formation which may limit the long-term success of the bypass procedure. The prevention of early bypass failure is challenged by the absence of a clear understanding of why vein bypasses fail and the lack of prior studies, which establish treatable risk factors such as excessive clot formation. Given that increasing use of medications to prevent clot formation is not harmless in patients after major surgery, the reliable identification of those at highest risk for excessive clot formation and at least risk for bleeding using point of care testing will provide a great clinical benefit. Furthermore, these studies will serve future efforts at genetic profiling to prospectively intervene and prevent excessive clot formation before it comes.