Theory 047/Medicine & Health /Clinical pharmacology
Anticoagulant Dose Is a Clearance Problem
Dosing is set once from weight and creatinine. Clearance changes with illness, and the dose does not.
Bleeding on anticoagulation is set by variability in renal clearance within a patient rather than by the average dose, so dose adjustment should track clearance changes rather than weight or creatinine at initiation.
01The evidence
Direct oral anticoagulants depend on renal clearance, and bleeding risk rises with declining renal function in a way that is only partly captured by baseline creatinine.
02The tension
Dosing algorithms use weight and baseline renal function, which are static, while clearance fluctuates with hydration, infection and interacting drugs.
03The mechanism
Plasma concentration is dose divided by clearance. If clearance varies within a patient, the same dose produces different exposures at different times, and bleeding tracks the peaks rather than the average.
That makes within-patient clearance variability the risk factor, and predicts that monitoring clearance trajectories should reduce bleeding more than weight-based adjustment.
04What this is not
Static dosing assumes stable clearance. This treats variability as the risk, which predicts bleeding from fluctuations.
05Predictions
- P1Bleeding should correlate with clearance variability.
- P2Trajectory-based adjustment should reduce bleeding.
- P3Weight adjustment should add little.
06Refutation
Bleeding tracking average exposure at controlled variability would restore static dosing.
07What it changes
It would add clearance monitoring to anticoagulation.