14. Hypoprothrombinemia
Hypoprothombinemia, with prolongation of the PT/INR, is most commonly due to vitamin K deficiency or liver disease. Certain drugs have been linked with hypoprothrombinemia, such as broad spectrum antibiotics, usually in patients who are also malnourished. Reports have linked sulfonamides, ampicillin, chloramphenicol, tetracyclines, and cefoxitin to deficiency in vitamin K-dependent clotting factors [71]. Cephalosporins may be associated with hypoprothrombinemia, especially those with the N-methyl-thiotetrazole (NMTT) side chain (e.g., moxalactam, cefoperazone), although these are no longer in common use [72].
For patients on warfarin, many drugs, especially antibiotics, are associated with increased hemorrhage. It is noted that there has been little systematic work on this subject, with the main sources being case reports [73]. Nonetheless, it is clear that many drugs interfere with coumadin through alteration of pharmacokinetics or dynamics (e.g., antibiotics, particularly quinolones, macrolides, and azoles), while others add to bleeding risk by their own mechanisms (e.g., aspirin, heparin, ticlopidine, and NSAIDs). Careful monitoring and dose adjustments are necessary when prescribing those medications to patients on warfarin.