cefoxitin and Hemorrhage

The core 1 beta1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcalpha1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen). The T antigen is a precursor for extended and branched O-glycans of largely unknown function. We found that wild-type mice expressed the NeuAcalpha2-3Galbeta1-3GalNAcalpha1-Ser/Thr primarily in endothelial, hematopoietic, and epithelial cells during development. Gene-targeted mice lacking T-synthase instead expressed the nonsialylated Tn antigen in these cells and developed brain hemorrhage that was uniformly fatal by embryonic day 14. T-synthase-deficient brains formed a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix. These data reveal an unexpected requirement for core 1-derived O-glycans during angiogenesis.

Topics: Animals; Antigens, Tumor-Associated, Carbohydrate; Antigens, Viral, Tumor; Blood Coagulation; Embryo, Mammalian; Endothelial Cells; Extracellular Matrix; Female; Galactosyltransferases; Gestational Age; Glycosylation; Hemorrhage; Humans; Mice; Mice, Knockout; Microcirculation; Neovascularization, Physiologic; Pericytes; Polysaccharides; Pregnancy; Tissue Distribution

Topics: Cefoxitin; Hemorrhage; Humans; Moxalactam; Postoperative Complications

Most cases of beta-lactam-associated coagulopathy occur in patients with other risk factors. This study analyzed temporally related clinical bleeding events in 1493 patients who received one antibiotic for at least three days. Univariate and multivariate analyses controlled for condition variables (nutritional status, renal, hepatic, or hematologic dysfunction, intensive care unit stay) and treatment variables (use of antiplatelet agents, anticoagulants, vitamin K, antitumor chemotherapy or antiulcer therapy, steroids) that could have been associated with bleeding independently. Rates of bleeding ranged from 0% (chloramphenicol sodium succinate, vancomycin hydrochloride, erythromycin lactobionate) to 8.2% (cefoxitin) to 22.2% (moxalactam disodium). Multiple logistic regression analyses revealed that only moxalactam (odds ratio, 9.9) and cefoxitin (odds ratio, 2.1) exhibited significantly higher likelihoods of bleeding than other agents. This study statistically confirms increased risk of bleeding with moxalactam, heretofore reported only anecdotally. Cefoxitin may carry risks greater than previously believed.

Topics: Anti-Bacterial Agents; Cefoxitin; Female; Hemorrhage; Humans; Male; Middle Aged; Moxalactam; Regression Analysis