Summary
There is good evidence that thrombolytic therapy induces a procoagulant state that retards the lytic process and triggers reocclusion. Thus, both in experimental animal systems and in humans, potent inhibitors of platelets and antithrombin Ill-independent thrombin inhibitors have been shown to be better than heparin at accelerating thrombolysis and preventing reocclusion. These in vivo observations have lent credence to the concept that elevated FPA levels that are suppressed by heparin reflect systemic activation of coagulation during the thrombolytic process. However, this concept may not be correct. Thus, when heparin is given in conjunction with plasminogen activators only modest increases in FPA levels are found, and our data suggest that this is due, at least in part, to the activity of enzymes other than thrombin. In the absence of concomitant heparin, thrombolytic therapy causes a much greater increase in the FPA values. These high FPA values are rapidly reduced by heparin, even though heparin has limited antithrombotic activity in the setting of pharmacologic thrombolysis. Based on these considerations, we believe that plasma FPA and desarginine FPB levels should not be used as specific markers of thrombin activity during the course of thrombolytic therapy and suppression of elevated FPA values by heparin should not be accepted as evidence that heparin is effective in this clinical setting.
