DETERMINANTS OF REBOUND THROMBIN ACTIVITY AFTER CESSATION OF HEPARIN IN PATIENTS UNDERGOING CORONARY INTERVENTIONS

This study was designed to characterize hemostatic activation (using f ibrinopeptide A (FPA), a marker of thrombin activity, and P-thromboglo bulin (BTG), a marker of platelet activation) sequentially in the coro nary and peripheral circulation in patients during percutaneous corona ry intervention (PCI) and several hours after PCI and discontinuation of heparin therapy. Heparin administered during PCI is known to nonuni formly suppress thrombin activity in the coronary, Persistent elevatio ns of FPA in coronary sinus (CS) blood during PCI have been associated with subsequent ischemic events. As a related consideration, rebound thrombin activity has been demonstrated in peripheral blood samples se veral hours after cessation of heparin therapy in patients with acute coronary syndromes. Accordingly, we hypothesized that increased thromb in activity occurs in the coronary circulation after PCl and is induce d by cessation of intravenous heparin to facilitate Vascular sheath re moval. Such a rebound prothrombotic effect, may contribute to suboptim al outcomes after PCI. In 21 patients undergoing PCI, heparin-bonded c atheters were employed to obtain sequential CS and femoral vein (FV) b lood samples for measurement in the coronary and peripheral circulatio n of plasma FPA, a marker of thrombin activity in vivo, and BTG releas ed by platelets during degranulation. Following heparin administration samples were obtained immediately prior to (base) and during (start a nd end) PCI. Late samples were obtained several hours after PCl(284 +/ - 46 min, mean +/- SD) following the cessation of heparin and prior to planned vascular sheath removal. Mean FPA concentration in CS blood w as low at baseline (3.82 +/- 2.09 ng/ml) and did not increase during P Cl, Mean FPA concentration in CS blood increased significantly several hours after cessation of heparin (3.42 +/- 2.36 vs. 7.82 +/- 9.98, en d vs. late, P < 0.001). In contrast, mean FPA concentration in FV bloo d was highest at baseline following vascular sheath insertion, decreas ed during PCI (69%, P < 0.05, base vs. end), and trended upward after PCI and cessation of heparin. Mean FPA values were higher at all times in FV compared with CS blood samples and were not concordant after PC I. Elevation of coronary circulation FPA after PCI was maximal in pati ents with myocardial infarction within 7 days (13.7 +/- 12.4 vs. 5.6 /- 7.9 ng/ml, P = 0.08), but was not influenced by heparin treatment p rior to PCI, a history of unstable angina, or coronary stent placement during PCI (9 of 21 patients). BTG values showed less variation than did FPA values, and cessation of heparin after PCI was not associated with an increase in BTG in CS or FV blood samples. An increase in thro mbin activity occurs in the coronary circulation after PCI following d iscontinuation of heparin, The extent of increased thrombin activity w as greatest in patients with recent myocardial infarction and was not exacerbated by coronary stent placement during PCI. This phenomenon ma y contribute to the important minority of ischemic complications early after PCI. (C) 1998 Wiley-Liss, Inc.