Intersubject variability in the anticoagulant response to heparin in vitro

The significance of baseline coagulation times and plasma concentrations of serine protease inhibitors as determinants of the relationship between heparin activity and its anticoagulant effect has been investigated in vitro. Citrated plasma was prepared from blood obtained from 20 normal subjects, and heparin added to yield concentrations ranging from 0.05 to 1.5 units/ml. The anticoagulant effect was determined by the activated partial thromboplastin time (APTT) and thrombin time (TT). An excellent linear relationship was observed between the natural logarithms (ln) of the coagulation times and heparin activity. Baseline APTT values ranged from 28.4 to 59.7 s and the slope values for the ln APTT vs heparin curves ranged from 1.488 to 3.427 ml/unit. Similar range was observed in the slope values for the ln TT vs heparin curves. There was a highly significant positive correlation between the ln APTT vs heparin slope values and the baseline APTT values (r: 0.905; p less than 0.001). There was also a weak but statistically significant positive correlation between plasma concentrations of alpha 2 macroglobulin and baseline APTT values (0.02 greater than 0 greater than 0.01) and slope values of the ln APTT vs heparin curves (0.02 greater than p greater than 0.01). Furthermore, there was a statistically significant positive correlation between plasma concentrations of alpha 1 antitrypsin and baseline TT values (0.05 greater than p greater than 0.02) and slope values of the 1n TT vs heparin (0.02 greater than p greater than 0.01). Neither baseline APTT and TT values nor slope values of the ln APTT and TT vs heparin curves were statistically significantly related to plasma concentrations of antithrombin III, fibrinogen, or alpha 1 acid glycoprotein. This study has demonstrated that baseline APTT is a major determinant of the anticoagulant response to heparin in vitro, as determined by that same coagulation test, and it illustrates that there is a wide intersubject variation in the anticoagulant response to heparin in vitro.