Lectin-induced aggregates of blood cells from patients with acute coronary syndromes.

BACKGROUND: Cell surface glycoligands and circulating glycoproteins are believed to contribute to the pathogenesis of acute coronary syndromes (ACS) through cell aggregation/adhesion mechanisms. To characterize the glycobiological status of blood cells from patients with ACS, we used an advanced lectin-mediated aggregation technique allowing for detection of not only conventional lectin-induced cell aggregates but also their fraction resistant to haptenic/inhibitory sugars. METHODS: Peripheral blood samples were obtained from 24 patients with acute myocardial infarction or unstable angina and 18 healthy control subjects. Two plant lectins, Viscum album agglutinin (VAA) and wheat germ agglutinin (WGA), were tested as cell aggregation stimuli binding to cell membrane beta-galactosides and N-acetyl-D-glucosamine acid residues, respectively. RESULTS: Two major types of differences were found between the clinical group and control: (1) VAA-induced aggregation of lymphocytes and platelets was decreased in ACS patients in comparison with healthy donors and (2) the stability of the lectin-induced cell aggregates was found to be an independent aggregation index that revealed opposite trends in the resistance of WGA-induced aggregates of platelets and neutrophils from ACS patients to haptenic sugars in comparison with respective controls. Thus, in the ACS group the stability of WGA-induced aggregates of platelets was impaired, whereas WGA-induced aggregates of neutrophils were more stable and their formation was accompanied by increased generation of H(2)O(2). CONCLUSIONS: We conclude that (a) glycobiological status of blood cells undergoes a complex remodeling in association with ACS and (b) detection of lectin-induced stable aggregates can serve as a sensitive method for determination of cellular dysfunctions in ACS.

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25.

AIMS: To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >or=75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than > 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis.