Antithrombin-III plasma activity during and after prolonged use of heparin in unstable angina

Heparin effectively prevents the complications of unstable angina but disease reactivation has been documented following its discontinuation. To investigate whether this could be related to antithrombin-III depletion, 50 patients with unstable angina had serial determinations of activated partial thromboplastin time and of the plasma levels of heparin, antithrombin-III activity and of the thrombin-antithrombin-III complex before, during and, in a subgroup of 8 patients, 4 hours after heparin discontinuation. Heparin was administered intravenously at therapeutic doses for a mean of 7.6 +/- 4.1 days. Plasma antithrombin-III activity decreased rapidly from 1.05 +/- 0.03 to 1.0 +/- 0.03 U/ml (p < 0.03) following heparin initiation with no further significant subsequent decrease. Antithrombin-III activity returned to the control values 4 hours after the discontinuation of heparin. Thus, heparin treatment is associated with small, non-cumulative and rapidly reversible decrease in antithrombin-III activity. Reactivation of unstable angina after discontinuation of heparin must be explained by a mechanism other than antithrombin-III deficiency.