Pathophysiology
Clinical meaning
The clinician independently prescribes, manages, and adjusts anticoagulation therapy, making complex decisions about agent selection, dosing, monitoring, drug interaction management, perioperative bridging, and reversal. Advanced prescribing considerations: WARFARIN pharmacogenomics -- CYP2C9 metabolizer status affects clearance (poor metabolizers need lower doses), and VKORC1 haplotype affects sensitivity (A/A genotype requires 50% lower dose than G/G). While pharmacogenomic-guided dosing algorithms exist, their clinical superiority over careful clinical titration remains debated. DOAC selection algorithm: for non-valvular AF, apixaban is preferred in elderly (lowest bleeding), rivaroxaban offers once-daily convenience, dabigatran has the only direct reversal agent (idarucizumab); for VTE, rivaroxaban and apixaban have simplified single-drug approaches (no heparin lead-in needed); for cancer-associated VTE, LMWH or edoxaban/rivaroxaban are preferred over warfarin. Renal dosing: dabigatran contraindicated if CrCl below 30 (US) or below 15; rivaroxaban dose-reduced at CrCl 15-50; apixaban dose-reduced if 2 of 3 criteria (age 80+, weight 60 kg or less, Cr 1.5+); edoxaban dose-reduced at CrCl 15-50, contraindicated above 95 (paradoxically less effective). Special populations: pregnancy (LMWH preferred; warfarin is teratogenic; DOACs are contraindicated), antiphospholipid syndrome (warfarin ONLY -- DOACs showed inferior outcomes in...