The effect of low dose nitroglycerin on plasma heparin concentrations and activated partial thromboplastin times.

We have investigated the effects of low dose nitroglycerin on the activated partial thromboplastin time (APTT), plasma heparin concentration, antithrombin III activity (AT-III) and platelet factor 4 (PF4) levels in a group of 42 patients receiving intravenous heparin and low dose nitroglycerin (GTN) following percutaneous transluminal coronary angioplasty (PTCA). Venous samples were taken before PTCA and at 2, 4 and 24 h after the start of the infusions. Despite the heparin infusion being constant, the median APTT ratio (interquartile range) was significantly lower at the 4 h sample time compared to the 2 h sample time (4.4 [3.8-4.5] vs 2.6 [1.8-4.0], P < 0.05). At this time there was also a significantly lower median plasma heparin concentration compared to the 2 h sample (0.35 [0.2-0.7] vs 0.17 [0.1-0.3] P < 0.05). There were no significant differences in AT-III activity or PF4 levels at 4 h compared to the 2 h sampling time. In another group of patients (n = 20) who received intravenous heparin alone following PTCA also at 1000 U/h there were no significant differences in median APTT ratios (4.4 [4.3-4.5] vs 4.2 [2.9-4.5]), or in median plasma heparin concentrations (0.26 [0.14-0.96] vs 0.22 [0.18-0.87]) at 4 h compared to 2 h. Our observations confirm that nitroglycerin can interfere with the anticoagulant effect of heparin even at low doses. Although the exact mechanism involved remains unknown, this study suggests it is likely to be a result of a reduction in plasma heparin levels, perhaps through acceleration of normal heparin elimination.