Differences in clot lysis among patients demonstrated in vitro with three thrombolytic agents (tissue-type plasminogen activator, streptokinase and urokinase).
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 dry-reagent 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Musselman
D R
DR
C. V. Richardson Cardiac Catheterization Laboratory, University of North Carolina Hospitals, Chapel Hill 27514.
Tate
D A
DA
Oberhardt
B J
BJ
Abruzzini
A F
AF
Blauwet
M B
MB
Koch
G
G
Dehmer
G J
GJ
D001780:Blood Coagulation Tests; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy; D015203:Reproducibility of Results; D013300:Streptokinase / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use
D007202:Indicators and Reagents; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator