1. Differences in clot lysis among patients demonstrated in vitro with three thrombolytic agents (tissue-type plasminogen activator, streptokinase and urokinase)
- Author
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Musselman, David R., Tate, David A., Oberhardt, Bruce J., Abruzzini, Anthony F., Blauwet, Mary Beth, Koch, Gary, and Dehmer, Gregory J.
- Subjects
Tissue plasminogen activator -- Health aspects ,Streptokinase -- Evaluation ,Urokinase -- Evaluation ,Blood clotting -- Drug therapy ,Drugs -- Testing ,Health - Abstract
This study compares the ability of 3 thrombolytic drugs to promote clot lysis using a new in vitro testing procedure. Whole blood samples from 132 patients were tested using 5 different concentrations of tissue-type plasminogen activator (t-PA), streptokinase (SK) and urokinase. A mixture of blood and thrombolytic drug was placed on a dryreagent test card containing reptilase, buffers and paramagnetic particles where clot formation occurred. Analysis of the motion of the clot-embedded paramagnetic particles caused by an oscillating magnetic field was used to define the lysis onset time. The slope of the linear regression plot of lysis onset time versus 1/[drug concentration] defined the kinetic rate constant (k) for each drug in each patient. Higher values of k indicated greater resistance to in vitro clot lysis. In the patients studied, there was a large range of k values for t-PA and SK (coefficient of variation 143 and 137%, respectively) but a smaller range of k for urokinase coefficient of variation 32%). The coefficients of variation for t-PA and SK observed in the study group were five- to 10-fold greater than the coefficients of variation determined for replicate test measurements. Resistance to all SK concentrations tested was found in 9% of the patients. in vitro sensitivity to thrombolysis was compared among the drugs by correlating the derived k values. These comparisons indicated no relation for any of the drugs; many patients had a relatively low k value for 1 drug, while having a relatively high k value for a different drug. Preliminary results in 6 patients with acute myocardial infarction tested prospectively with a clinical version of this system identified 1 patient in whom there likely was a failure of the thrombolytic drug. These data suggest that in vitro testing before the administration of a thrombolytic drug is feasible and may be clinically useful in determining the drug choice for an individual patient. (Am J Cardiol 1994;73:544-549)
- Published
- 1994