Author + information
- Received February 11, 1994
- Revision received July 4, 1994
- Accepted August 22, 1994
- Published online January 1, 1995.
- Piera Angelica Merlini, MD∗,a,
- Kenneth A Bauer, MD∗,1,
- Luigi Oltrona, MDa,
- Diego Ardissino, MD†,
- Alessandra Spinola, MDa,
- Marco Cattaneo, MD‡,
- Marco Broccolino, MDa,
- Pier Mannuccio Mannucci, MD‡ and
- Robert D Rosenberg, MD, PhD∗,§,2
- ↵∗Address for correspondence: Dr. Piera Angelica Merlini, Second Division of Cardiology, Ospedale Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
Objectives. This prospective study investigated the behavior of thrombin generation and activity during thrombolysis and concomitant heparin administration.
Background. It has been shown that during thrombolytic therapy there is an increase in thrombin generation and activity. Increased thrombin activity is suppressed by concomitant intravenous heparin, but it is unknown whether thrombin generation is also affected.
Methods. Thrombin generation was assessed by measuring prothrombin fragment 1 + 2 and thrombin—antithrombin complex plasma levels and thrombin activity by measuring fibrinopeptide A plasma levels. Serial blood samples were obtained before and at 90 min and 24 and 48 h after the administration of streptokinase (15 patients), recombinant tissue-type plasminogen activator (15 patients) or anistreplase (13 patients). An intravenous bolus of heparin (5,000 IU) was administered before the start of thrombolytic therapy, followed by an infusion of 1,000 U/h to maintain an activated partial thromboplastin time >1.5 times baseline.
Results. During thrombolytic and concomitant heparin therapy, there was an increase in the plasma levels of prothrombin fragment 1 + 2 (baseline 1.08 vs. 2.73 nmol/liter, p < 0.001) and thrombin—antithrombin complex (baseline 6.5 vs. 17.1 μg/ml, p < 0.01) at 90 min, whereas no change was observed in fibrinopeptide A at 90 min (baseline 2.8 vs. 3.0 nmol/liter, p = NS).
Conclusions. During thrombolytic therapy with both fibrinspecific and non—fibrin-specific drugs, there is an increase in thrombin generation despite concomitant administration of intravenous heparin.
↵1 Dr. Bauer is an Established Investigator of the American Heart Association, Dallas, Texas.
↵2 Dr. Rosenberg is a consultant to the Baxter-Dade Company, Miami, Florida.
☆ This work was supported by Grant HL33014 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
- Received February 11, 1994.
- Revision received July 4, 1994.
- Accepted August 22, 1994.