Author + information
- Received August 1, 1996
- Revision received March 10, 1997
- Accepted May 30, 1997
- Published online July 1, 1997.
- Russell P Tracy, PhDA,*,
- Deborah Z Rubin, MDB,
- Kenneth G Mann, PhDC,
- Edwin G Bovill, MDA,
- Matthew Rand, PhDC,
- Dominic GeffkenA and
- Paula B Tracy, PhDC
- ↵*Dr. Russell P. Tracy, University of Vermont, Aquatec Building T205, 55A South Park Drive, Colchester, Vermont 05446. E-mail: firstname.lastname@example.org.
Objectives. We sought to determine the extent of Factor V proteolysis during thrombolytic therapy.
Background. Thrombin- or Factor Xa–activated Factor V is an essential cofactor in the prothrombinase complex. In purified systems, plasmin, the major product of thrombolytic therapy, is known to first activate then inactivate Factor V.
Methods. We used quantitative gel electrophoresis and Western blotting to analyze the cleavages in plasma Factor V after thrombolytic therapy.
Results. The addition of streptokinase to plasma resulted in the activation then inactivation of Factor V, confirming previous results using purified reagents. We also identified the Factor V fragments resulting from the action of thrombin and plasmin. After thrombolytic therapy, there was considerable Factor V cleavage. The cleavage patterns were consistent with the action of plasmin, with little evidence for the action of thrombin. In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (n = 17), we observed an average 58% loss of intact Factor V at 6 h (range 1% to 91%). Samples from the Thrombolysis in Myocardial Infarction trial, Phase II (n = 12), collected on a shorter time scale, showed a loss of up to 99% at 50 min, with the loss of intact Factor V associated with the plasma concentration of plasminogen activator. Samples from patients with bleeding (n = 12) showed extensive Factor V cleavage.
Conclusions. Factor V cleavage in thrombolytic therapy is primarily plasmin mediated, rapid and often extensive. It is likely that transient increases, as well as longer term losses, of Factor V cofactor activity play a role in both ischemic and hemorrhagic events subsequent to thrombolytic therapy. The extensive loss of Factor V in some patients may affect the estimation of heparinization.
☆ This study was supported by Public Health Service Grants HL 35058 and HL 46703 (to Dr. Tracy), Grant HL 38460 (to Drs. Mann and Tracy) and Training Grant HL 07594 (to Dr. Rubin) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
- Received August 1, 1996.
- Revision received March 10, 1997.
- Accepted May 30, 1997.