Relationship between concentration and anticoagulant effect of heparin in plasma of normal subjects: Magnitude and predictability of interindividual differences*

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Abstract
The purposes were to determine the magnitude of inter- and intraindividual variations in the relationship between heparin concentration and anticoagulant effect in normal adults and to determine whether these variations are associated with, and predictable from, certain physiologic characteristics of individual subjects. Citrated plasma was obtained from 12 men and 5 women, 21-35 yr old. Heparin was added to the plasma to yield concentrations of 0.05-1.0 U/ml and the activated partial thromboplastin time (APTT) was determined. These studies were repeated once or twice over 65 days. Baseline APTT values (i.e., APTT without added heparin) ranged from 25.6-36.2 s and the hematocrit ranged from 39-50%. Both measures showed little intrasubject variation on the same day or on different days. There was an excellent linear relationship between ln APTT and heparin concentration in the 0.05-0.8 U/ml range (r2 > 0.987 in all cases). The slope value for this relationship ranged from 1.51-3.88 ml/U and these interindividual differences were well reproducible on repeated testing. Women had lower hematocrits (P < 0.05) and higher slope values (P < 0.01) than men. Multiple linear regression analysis revealed a linear relationship between observed slope values and slope values calculated as a function of both hematocrit and baseline APTT. Age, weight and the concentrations of various plasma proteins did not contribute significantly to the predictability of the slope. A multiple linear regression equation with hematocrit and baseline APTT as independent variables yielded a multiple correlation coefficient of 0.875 (P < 0.01). It may be possible to predict the APTT value produced by a given concentration of heparin in an individual subject from that subject''s baseline APTT and hematocrit.