Can a Patient Take Nitroglycerin While on a Heparin Drip?
Yes, a patient can safely receive nitroglycerin while on a heparin drip, but close monitoring of anticoagulation parameters is essential because nitroglycerin may interfere with heparin's anticoagulant effect in some patients, requiring dose adjustments. 1, 2
Primary Considerations
Drug Interaction Profile
The FDA label for heparin explicitly states that "intravenous nitroglycerin administered to heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin," and recommends "careful monitoring of partial thromboplastin time and adjustment of heparin dosage during coadministration." 2
The key clinical implication is that you must monitor aPTT more frequently (not just at standard intervals) and be prepared to increase heparin doses while nitroglycerin is running, then decrease heparin when nitroglycerin is stopped to avoid hemorrhage. 2, 3
Clinical Context Where This Combination is Standard Practice
This combination is routinely used and explicitly recommended in acute coronary syndromes. The 2014 AHA/ACC guidelines state that intravenous nitroglycerin is beneficial in patients with heart failure, hypertension, or symptoms not relieved with sublingual nitroglycerin, and these patients are typically already receiving anticoagulation including heparin. 4
Evidence on the Interaction
Conflicting Research Findings
The evidence regarding clinically significant heparin resistance from nitroglycerin is mixed:
Early reports (1987) documented marked heparin resistance requiring frequent aPTT monitoring, with patients becoming resistant to heparin during IV nitroglycerin and showing increased sensitivity when nitroglycerin was discontinued. 3
Dose-dependent effect (1990) found that heparin resistance occurred only at nitroglycerin doses exceeding 350 mcg/min, mediated through a qualitative antithrombin III abnormality. 5
More recent studies (1994-1995) found no significant interaction at clinically relevant nitroglycerin doses (5-240 mcg/min), with no difference in heparin dose requirements between patients receiving nitroglycerin versus those not receiving it. 6, 7
Practical Interpretation
The interaction appears dose-dependent and clinically significant primarily at higher nitroglycerin infusion rates (>350 mcg/min), but given the FDA warning and early case reports, monitoring is warranted at all doses. 2, 5
Monitoring Protocol
When using both medications concurrently:
Check aPTT more frequently than standard protocol (every 4-6 hours initially rather than every 12 hours) to detect any reduction in anticoagulant effect. 2, 3
Anticipate needing higher heparin doses while nitroglycerin is infusing, particularly if nitroglycerin doses exceed 100-200 mcg/min. 3, 5
Reduce heparin dose proactively when discontinuing nitroglycerin to prevent rebound over-anticoagulation and bleeding risk. 2, 3
Recheck aPTT within 4-6 hours after any change in nitroglycerin dose or discontinuation. 2
Absolute Contraindications to Nitroglycerin (Regardless of Heparin Use)
Do not administer nitroglycerin if the patient has:
Hypotension (SBP <90 mm Hg or ≥30 mm Hg below baseline). 4
Recent phosphodiesterase inhibitor use (within 24 hours of sildenafil/vardenafil or 48 hours of tadalafil). 4
Right ventricular infarction, where preload reduction can cause hemodynamic collapse. 4
Severe bradycardia (<50 bpm) or tachycardia (>100 bpm in absence of heart failure). 4
Clinical Bottom Line
The combination of IV nitroglycerin and heparin is not contraindicated and is frequently used together in acute coronary syndromes, but requires enhanced aPTT monitoring with dose adjustments of heparin both during concurrent use and upon nitroglycerin discontinuation. 4, 2 The interaction is real per FDA labeling but appears most clinically significant at higher nitroglycerin doses, and modern studies suggest it may be less problematic at typical clinical doses than early reports suggested. 6, 7, 5