title: Effects of moxalactam on blood coagulation and platelet function.
abstract: Bleeding complications have occasionally been reported in clinical trials of moxalactam therapy for debilitated and/or malnourished patients. Complications that occur secondary to hypothrombinemia are readily corrected by administration of 5-10 mg of vitamin K. In a few instances, the bleeding complications occurred secondary to suppression of platelet function. The present studies aim at clarifying the mechanisms by which bleeding problems attributable to moxalactam and other beta-lactam antibiotics occur. Moxalactam in vitro did not inhibit blood coagulation or platelet aggregation at concentrations of 700 micrograms of moxalactam/ml. When administered to five normal male volunteers at a dosage of 3 g of moxalactam four times daily for seven days, the antibiotic did not affect the levels of vitamin K-dependent clotting factors II, VII, IX, and X or vitamin K-independent clotting factors V, VIII, and I. Consistently normal levels of the abnormal prothrombin precursor descarboxyprothrombin, as determined by immunochemical and functional assays, showed that moxalactam did not possess warfarin-like properties. Moxalactam induced a significant suppression of adenosine diphosphate (ADP)-induced platelet aggregation. It appears that moxalactam inhibits ADP-induced platelet aggregation in vivo by perturbing the platelet membrane, thus making ADP receptors unavailable to the agonist. Of 33 additional beta-lactam antibiotics tested, 27 were found to suppress ADP-induced aggregation at high concentrations in vitro. It is concluded that moxalactam, as well as many newer and older broad-spectrum antibiotics, causes bleeding complications in debilitated patients by elimination of vitamin K-producing gut microorganisms. However, the clinical implications of the observed suppression of platelet function by many beta-lactam antibiotics are unclear.
mesh_terms: D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D002513:Cephamycins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008315:Malondialdehyde / Q000097:blood; D009070:Moxalactam; D010974:Platelet Aggregation / Q000187:drug effects; D011498:Protein Precursors; D011516:Prothrombin / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors; D014812:Vitamin K / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D002511:Cephalosporins; D002513:Cephamycins; D011498:Protein Precursors; D014812:Vitamin K; D008315:Malondialdehyde; C008208:acarboxyprothrombin; D011516:Prothrombin; D009070:Moxalactam