Human plasma extrinsic pathway inhibitor activity: I. Standardization of assay and evaluation of physiologic variables

Abstract

An assay was standardized to measure extrinsic pathway inhibitor (EPI) activity in human plasma. Variables that could potentially influence its measurement were systematically examined. The coefficient of variation of the assay was 6.3% for the same sample assayed on different days. The linear regression line for a plot of observed v expected values of mixtures of plasmas with different EPI levels was Y = 1.01X - 2.7%. Single samples from 21 healthy adults under 60 years of age varied between 74% and 159% of a pooled reference plasma. The plasma level of a given individual (eight subjects) did not vary on repeat sampling over weeks to months. EPI activity was significantly lower in plasma from umbilical cord blood (64.3% ± 12.7%, n = 16) than in plasma from adults. Mean EPI activity in adults ≥ 60 years of age was slightly but significantly higher (112% ± 16.8%, n = 23) than in adults < 60 years of age (97.2% ± 19.0%, n = 21). EPI levels in the third trimester of pregnancy were slightly higher than in nonpregnant women. Plasma EPI levels fell slightly after surgical procedures that caused fibrinogen levels to rise, which suggests that EPI is not an acute phase reactant. Administration of 1-desamino-8-d-arginine vasopressin (DDAVP) did not alter plasma EPI levels. In two patients subjected to plasmapheresis and volume replacement with albumin and isotonic saline, plasma EPI levels returned to one-half of the levels before pheresis within about one day.