Heparin-binding proteins are involved in thrombin time variability in normal and patient plasmas

The ability of plasma proteins to neutralize the anticoagulant activity of heparin was studied using a thrombin time assay with 20 normal adult and 20 7 patient plasma samples. The thrombin times of normal adult plasmas spiked with the same amount of heparin were found to vary significantly, and this variability was attributed to differences in heparin-binding proteins amon g individuals. This possibility was investigated by determining thrombin ti mes for a variety of plasma samples following proteolytic digestion. A stud y of patient pooled plasma showed that incubation with a protease increased the thrombin time from 23 s to > 300 s, suggesting that the anticoagulant activity of heparin could be neutralized by plasma proteins and released wi th proteolytic digestion. Incubation of the digested plasma with heparinase I returned the thrombin time almost to control values. In addition, patien ts who received prior heparin injections had different responses to similar dosages of heparin, as indicated by differences in thrombin times. Thus, t he anticoagulant activity of heparin may be affected by the balance between free heparin and protein-bound heparin in plasma. (C) 2000 Lippincott Will iams & Wilkins.