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Effects of moxalactam on blood coagulation and platelet function

, : Effects of moxalactam on blood coagulation and platelet function. Reviews of Infectious Diseases 4 Suppl: S546-S554

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.


PMID: 6218565

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