B01: Antithrombotic agents

Part of B: Blood and blood forming organs.

Delayed effect is the default. Vitamin K antagonists suppress synthesis of clotting factors [1], and irreversible antiplatelet agents outlast the drug [2], so effect follows the turnover of a protein or cell pool rather than plasma concentration. Turnover and indirect response models are the natural starting point [3,4].

The exception worth knowing. Direct oral anticoagulants inhibit an existing enzyme, so their effect on clotting assays tracks concentration with little delay and direct models are what is actually fitted [5–7].

Benefit-risk is asymmetric. Exposure-response detects the bleeding limb far more reliably than the efficacy limb, which is often flat across the range studied [8,9]. Covariates that raise exposure (renal function, body size, age, P-glycoprotein and CYP3A inhibitors) move bleeding first, which is why dose-reduction criteria are written in exactly those terms [10,11].

Mechanistic extrapolation. QSP models of the coagulation network, built from literature kinetics, are well established for predicting how anticoagulants shift thrombin generation and INR, extrapolating efficacy and bleeding risk across doses [12,13].