THE EFFECT OF DIFFERENT NITRATE PREPARATIONS ON PLASMA HEPARIN CONCENTRATIONS AND THE ACTIVATED PARTIAL THROMBOPLASTIN TIME

There is evidence that intravenous nitrates which are frequently used in acute coronary syndromes map interfere with the anticoagulant effec t of heparin. We compared the effect of two different nitrate preparat ions on the activated partial thromboplastin time (APTT), anti-thrombi n III activity (AT III) and plasma heparin levels in patients (n = 50) undergoing routine percutaneous transluminal coronary angioplasty (PT CA) for stable angina. Patients were randomized to either: (1) intrave nous heparin and nitroglycerine (GTN); or (2) intravenous heparin and isosorbide dinitrate. The APTT, plasma heparin concentration and AT II I activity were measured before PTCA and at 2 and 4 hours after commen cement of infusions. Both groups received identical doses of heparin. Group 1 patients received a constant dose of 16.6 mu g/minute of GTN, and group 2 patients received 33.3 mu g/minute of isorbide dinitrate. At 4 hours the median APTT ratio was significantly lower in group 1 co mpared with group 2 (2.6 versus 4.5) (P < 0.05) as was the plasma hepa rin 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 m activity was not si gnificantly different between the groups at any sample time. Within-gr oup analysis showed significantly lower APTT ratio and heparin concent rations at 4 hours compared with the respective 2 hour values. These r esults would suggest that there is a potential impairment of anticoagu lation 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 us ed in combination.