DIFFERENCES IN CLOT LYSIS AMONG PATIENTS DEMONSTRATED IN-VITRO WITH 3THROMBOLYTIC AGENTS (TISSUE-TYPE PLASMINOGEN-ACTIVATOR, STREPTOKINASEAND UROKINASE)

This study compares the ability of 3 thrombolytic drugs to promote clo t lysis using a new in vitro testing procedure. Whole blood samples fr om 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 dry-reagent t est card containing reptilase, buffers and paramagnetic particles wher e clot formation occurred. Analysis of the motion of the clot-embedded paramagnetic particles caused by an oscillating magnetic field was us ed to define the lysis onset time. The slope of the linear regression plot of lysis onset time versus 1/[drug concentration] defined the kin etic rate constant (k) for each drug in each patient. Higher values of k indicated greater resistance to in vitro clot lysis. In the patient s studied, there was a large range of k values for t-PA and SK (coeffi cient of variation 143 and 137%, respectively) but a smaller range of k for urokinase (coefficient of variation 32%). The coefficients of va riation for t-PA and SK observed in the study group were five- to 10-f old greater than the coefficients of variation determined for replicat e test measurements. Resistance to all SK concentrations tested was fo und in 9% of the patients. In vitro sensitivity to thrombolysis was co mpared among the drugs by correlating the derived k values. These comp arisons 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 acu te 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 be fore the administration of a thrombolytic drug is feasible and may be clinically useful in determining the drug choice for an individual pat ient.