Summary
Blood samples were collected from 43 patients undergoing elective cardiac surgery
to determine the extent of thrombin generation and inhibition in patients when receiving
heparin while undergoing cardiopulmonary bypass (CPB). Plasma prothrombin fragment
F1 + 2 and thrombin-antithrombin III (TAT) levels were measured as markers of thrombin generation
and inhibition, respectively. Both F1 + 2 and TAT levels increased significantly during the course of CPB despite the heparin
causing significant systemic anticoagulation, i.e. the activated coagulation time
(ACT) was prolonged to greater than 400 s throughout the entire surgical procedure.
The extent of thrombin generation increased with time on CPB but did not differ between
patients receiving normothermic and hypothermic cardioplegia during CPB. Furthermore,
thrombin generation increased following the neutralization of the heparin with protamine
sulphate, and continued to be elevated significantly 24 h post surgery. The observation
that high dose heparin did not prevent thrombin generation during CPB, is consistent
with previous experimental studies demonstrating that thrombin bound to fibrin or
other surfaces (e.g. the CPB conduit) is resistant to antithrombin III/heparin inhibition,
and thus able to facilitate further thrombin generation. The observation that thrombin
generation continued to be elevated post surgery i.e. 24 h after neutralizing the
heparin with protamine sulphate, suggests that the high dose heparin did not inhibit
effectively all of the thrombin that had been generated. Thus, CPB patients may be
at risk not only of bleeding and other side-effects associated with the acute use
of high dose heparin, but may also be at risk of further thrombosis-related events
either acutely or chronically.
