Monitoring of heparin therapy: should heparin assays also reflect the patient's antithrombin concentration?

Chromogenic substrate (CS) assay of heparin may be performed with or without addition of antithrombin (AT) to the test plasma. Both types of assay are used for monitoring of heparin therapy, reflecting either heparin activity (heparin act), or heparin concentration (heparin conc) when AT is added. In plasma samples from 43 patients treated with intravenous heparin for DVT, the ratio between heparin act and heparin conc varied from 0.36 in patients with AT plasma concentration below 0.50 U/ml, to 0.85 in patients with AT above 1.00 U/ml (mean ratio 0.61). A formula expressing heparin act as a function of AT and heparin concentration in the test plasmas of the patients was used to calculate heparin act of the total material comprising 280 patients. Mean heparin act and heparin conc were both significantly correlated to clinical outcomes (bleeding complications, pulmonary embolism and phlebography score). For monitoring heparin therapy, guidelines for plasma heparin activity or concentration ("therapeutic ranges") are requested. When using a heparin act assay, the heparin dose needed in patients with low plasma AT concentration to reach a fixed therapeutic range, may imply undue risk of bleeding. On the other hand, when a heparin conc assay indicate plasma heparin conc within therapeutic range, antithrombotic activity may still be inadequate in patients with low plasma AT concentration.