Hemostatic alterations associated with supraceliac aortic cross-clamping

Purpose: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. Methods:. To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (111) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time ( PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PIT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and alpha,2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests. Results: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in PIT levels (P =.005), a decrease in FBG levels (P <.001), and a trend toward PTT prolongation (P =.06) compared with baseline. In contrast, there were no changes in PTT, PIT levels, or FBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P =.04), remained elevated 5 minutes after unclamping (P =.08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P <.001) and 5 minutes after unclamping (P =.002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of alpha,2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline. Conclusion: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR mid SC AXC result in decreased fibrinolytic activity ("fibrinolytic shutdown") after release of the aortic clamp.