Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality.
An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.
Becker
R C
RC
Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester.
Corrao
J M
JM
Bovill
E G
EG
Gore
J M
JM
Baker
S P
SP
Miller
M L
ML
Lucas
F V
FV
Alpert
J A
JA
D000328:Adult; D000368:Aged; D000941:Antigens / Q000032:analysis; D000990:Antithrombin III / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D003327:Coronary Disease / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use*; D010314:Partial Thromboplastin Time
D000941:Antigens; D000990:Antithrombin III; D006493:Heparin; D005996:Nitroglycerin