The role of tissue factor in patients undergoing open repair of ruptured and nonruptured abdominal aortic aneurysms
Received 21 February 2007; accepted 23 May 2007. published online 31 August 2007.
Background
Ruptured abdominal aortic aneurysm (AAA) is associated with the development of a procoagulant and hypofibrinolytic state. Tissue factor (TF) and its naturally occurring inhibitor, tissue factor pathway inhibitor (TFPI), play a central role in the initiation and progression of such a hypercoagulable state, but their role in patients undergoing open AAA repair has not previously been examined.
Methods
A prospective study was conducted of 17 patients undergoing elective AAA repair and 10 patients undergoing emergency AAA repair. Blood was taken before induction, and 5 minutes, 24 hours, and 48 hours after aortic cross-clamp release and assayed for plasma TF, TFPI, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), and thrombin-activatable fibrinolysis inhibitor (TAFI) activities.
Results
TF activity was significantly higher at all time points in patients with ruptured AAA compared with nonruptured AAA. The median (interquartile range, IRQ) TF activity (AU/mL) was 9.9 vs 3.2 (IRQ, 5.9 to 12.6 vs 2.0 to 7.6; P = .005) at preinduction; 10.7 vs 1.5 (IRQ, 9.2 to 18.3 vs 0.1 to 6.6; P = .003) at 5 minutes after clamp release; 9.5 vs 3.3 (IRQ, 7.0 to 13.5 vs 1.0 to 7.9; P = .013) at 24 hours, and 9.6 vs 3.9 (IRQ, 7.6 to 12.6 vs 2.4 to 8.7; P = .006) at 48 hours. TFPI levels were not significantly different between ruptured AAA and nonruptured AAA before or during operation but became significantly elevated at 24 and 48 hours in patients who had undergone repair of ruptured AAA. Ruptured AAA repair was associated with a hypofibrinolytic state compared with nonruptured AAA.
Conclusions
The present study has demonstrated for the first time, to our knowledge, that ruptured AAA is associated with significantly higher perioperative levels of circulating TF compared with nonruptured AAA. Furthermore, in the immediate perioperative period, the high levels of TF are not associated with a corresponding rise in TFPI levels, indicating an unopposed prothrombotic state. Direct inhibition of TF by administration of anti-TF antibodies or recombinant TFPI remains to be evaluated in subjects presenting with hemorrhage due to ruptured AAA, but if given early enough, it may attenuate the early deleterious effects of unopposed TF expression and ultimately contribute to improved outcomes.
aUniversity Department of Vascular Surgery, Heart of England National Health Service Foundation Trust, Birmingham, UK
bUniversity Department of Haematology, Heart of England National Health Service Foundation Trust, Birmingham, UK.
Reprint requests: Donald J. Adam, University Department of Vascular Surgery, Heart of England NHS Foundation Trust, Netherwood House, Solihull Hospital, Birmingham B91 2JL, UK.
ABSTRACT