Heparin cofactor II: experimental approach to a new assay and clinical results.

By a series of experiments it could be shown that an activity test of heparin cofactor II (HC II) is only specific after a complete depletion of antithrombin III. Also when dermatan sulfate which does not enhance the action of AT III is used for the activation of HC II there is a considerable influence on the remaining thrombin activity which alters the test results. Furthermore, in a system which contains plasma as well as thrombin the formation of a clot is likely to occur which by its opacity influences photometric results. A chromogenic substrate assay is described which excludes the influence of these variables. This assay was used to examine the activity of HC II in healthy persons as well as in patients. Three members of a family were found who had a heterozygous deficiency of HC II without any history of thrombosis. On the other hand, a total of 16 patients with heterozygous deficiency of HC II suffered from recurrent thromboembolic episodes. For this reason it is assumed that a deficiency of HC II has a certain importance in the occurrence of thrombophilia though it is apparently less thrombogenic than a deficiency of other inhibitors.