RESUMO
Background: Besides its anticoagulant effects, heparin is known to alter platelet (PLT) function. We examined the effects of unfractionated heparin on PLT function in patients with stable coronary artery disease (CAD). Methods and Results: PLT function was evaluated by whole-blood flow cytometry to detect PLT CD62 expression and by impedance aggregometry to assess the platelet aggregation (PA) before and after bolus intravenous administration of low-dose heparin (2713 +/- 1231 U) in 16 patients undergoing coronary angiography (group 1) and high-dose heparin (7937 +/- 2414 U) in 16 patients undergoing coronary angioplasty (group 2). Activated clotting time (ACT) and plasma antifactor-Xa heparin levels also were measured. Heparin increased PLT CD62 expression, which was significantly more pronounced in group 1 patients with plasma heparin levels less than 0.7 U/mL and ACT of 222 +/- 52 seconds compared with group 2 patients with heparin levels greater than 0.7 U/mL and ACT of 365 +/- 86 seconds (8 +/- 9 v -1 +/- 4% change in resulting PLTs, P =.01, and 11 +/- 12 v 1 +/- 6% increase in adenosine diphosphate (ADP) [5 µM]-stimulated PLTs, P =.02). Heparin produced a slight increase in PA in group 1 patients (1.4 +/- 5.3 ohms) as compared with the group 2 patients, where it significantly suppressed PA (-3.0 +/- 5.3 ohms, P.05 v group 1). A strong and statistically significant negative correlation between change in platelet CD62 expression and heparin concentration was observed in group 1 patients (r = -.5, P =.05, -ADP; r = -.65, P =.006, +ADP), whereas this relationship was weak and did not reach statistical significance in group 2 patients (r = -0.4, P =.2, -ADP; r =.11, P = 0.9; +ADP). Conclusion: Bolus administration of intravenous heparin augmented PLT activation in patients at clinically relevant anticoagulant concentrations (<0.7 U/mL). These findings may have implications for optimal dosing strategy for heparin as an antithrombotic agent in clinical situations characterized by platelet-dependent thrombotic events.
RESUMO
BACKGROUND: Nitric oxide (NO) plays an important role in modulating platelet-vessel wall interaction following vascular injury. We exampled the effects of local infusion of an ultra-short-acting NO-releasing compound: NO adduct of N, N'-dimethylhexanediamine (DMHD/NO), sodium nitroprusside, intravenous nitroglycerin, and aspirin on acute platelet-thrombus formation under conditions of high-shear blood flow in a rabbit extracorporeal perfusion model. MATERIALS AND METHODS: Strips of porcine aortic media were perfused in a Badimon chamber with arterial blood from 20 New Zealand White rabbits for 10 minutes at a shear rate of 1700 s(-1). Thrombus formation was quantified by morphometric analysis of thrombus area. Effects on collagen-induced platelet aggregation, blood pressure, bleeding time, and activated clotting time were also examined. RESULTS: DMHD/NO inhibited thrombus area and platelet aggregation in a dose-dependent manner with a 90% reduction in thrombus area (0.018 +/- 0.039 vs 0.215 +/- 0.085 mm(2)/mm control, P <.001) and a 50% reduction in platelet aggregation (4.8 +/- 4.4 vs 9.9 +/- 4.1 Omicron control, P =.04) at the highest dose of 1.0 nM/kg and 100 µM/L, respectively, without any effects on blood pressure, bleeding time, or activated clotting time. In contrast, equimolar concentrations of sodium nitroprusside and intravenous nitroglycerin had significantly reduced effects on thrombus area compared to DMHD/NO and were associated with significant reductions in blood pressure and prolongation of bleeding time. Aspirin had no effect on thrombus area at 1 µM/kg but reduced thrombus area and prolonged bleeding time at 2 and 5 µM/kg. CONCLUSIONS: Local delivery of DMHD/NO produced a 90% inhibition of experimental acute platelet-thrombosis under high-shear flow conditions without producing adverse systemic hemodynamic or hemostatic effects. Thus, inhibition of thrombus formation by local delivery of a rapidly acting NO donor may be an effective strategy for prevention of arterial injury-induced thrombosis.
RESUMO
Little data exist on the value of intravenous thrombolysis for acute myocardial infarction in patients with previous coronary bypass surgery. The Thrombolysis In Myocardial Infarction (TIMI) 4 trial was a randomized study comparing tissue plasminogen activator, anistreplase, or a combination in patients with evolving myocardial infarction; patients with previous coronary bypass surgery were not excluded. Coronary angiography was performed 90 minutes and 18-36 hours after randomization, a myocardial perfusion scan was performed at 18-36 hours and predischarge, and a radionuclide ventriculogram was obtained predischarge. Angiographic and clinical outcome variables were determined in patients with and without a history of coronary bypass surgery. A total of 416 patients were randomized and 13 of them had previous bypass surgery; of these, 6 had an occluded vein graft as the infarct-related vessel. The incidence of TIMI grade 3 flow at 90 minutes was lower in patients with previous coronary surgery as compared with controls (42% vs. 49%), and overall patency was significantly lower (50% vs. 77%, p = 0.04). This trend persisted at 18-36 hours after randomization. Furthermore, patients with previous coronary surgery had more thrombus in their infarct-related arteries, especially with occlusion of a vein graft (83% vs. 32%, p = 0.04) and higher rates of recurrent ischemia (15% vs. 8%) and recurrent infarction (23% vs. 5%, p = 0.03) than controls. Thus, in patients with previous coronary bypass surgery intravenous thrombolysis yields results that are inferior to those achieved in patients without such a history and alternative methods of reperfusion should be considered.
