The effect of different nitrate preparations on plasma heparin concentrations and the activated partial thromboplastin time

Abstract

There is evidence that intravenous nitrates which are frequently used in acute coronary syndromes may interfere with the anticoagulant effect of heparin. We compared the effect of two different nitrate preparations on the activated partial thromboplastin time (APTT), anti-thrombin III activity (AT III) and plasma heparin levels in patients (n = 50) undergoing routine percutaneous transluminal coronary angioplasty (PTCA) for stable angina. Patients were randomized to either: (1) intravenous heparin and nitroglycerine (GTN); or (2) intravenous heparin and isosorbide dinitrate. The APTT, plasma heparin concentration and AT III activity were measured before PTCA and at 2 and 4 hours after commencement of infusions. Both groups received identical doses of heparin. Group 1 patients received a constant dose of 16.6 μg/minute of GTN, and group 2 patients received 33.3 gig/minute of isorbide dinitrate. At 4 hours the median APTT ratio was significantly lower in group 1 compared with group 2 (2.6 versus 4.5) (P< 0.05) as was the plasma heparin concentration (0.18 U/ml versus 0.32 U/ml (P <0.05). However, no significant difference in APTT ratios or plasma heparin concentrations were noted at any of the other sample times. AT III activity was not significantly different between the groups at any sample time. Within-group analysis showed significantly lower APTT ratio and heparin concentrations at 4 hours compared with the respective 2 hour values. These results would suggest that there is a potential impairment of anticoagulation with low-dose intravenous nitroglycerine and to a lesser extent with low-dose isosorbide dinitrate. Early and frequent monitoring may therefore be appropriate when intravenous nitrates and heparin are used in combination.